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Objective: Recent research suggests curcumin extracted from the turmeric plant may inhibit the proliferation of cancer cells by controlling the expression of microRNAs (miRNAs). The effect of phenolic curcumin on miR-638-5p and potential target gene expressions in the triple negative breast cancer (TNBC) cell line MDA-MB-231 was investigated in this study. Materials and Methods: GSE154255 and GSE40525 datasets were downloaded and analyzed using GEO2R to identify dysregulated miRNAs in TNBC. To find differently expressed genes in breast cancer (BRCA), The Cancer Genome Atlas Program data was examined. Utilizing in silico tools, KEGG, GO, and other enrichment analyses were performed. The databases miRNet, miRTarBase v8.0, and TarBase v.8 were used for miRNA and mRNA matching. Real-time quantitative reverse transcription polymerase chain reaction was used to examine the levels of miRNA and its targets in miRNA mimic transfected/curcumin-treated MDA-MB-231 cultures and controls. The cell viability detection kit-8 method was used to assess cell viability, and the scratch assay was used to conduct migration assessment. Results: Bioinformatics analysis showed that miR-638-5p was significantly reduced in TNBC patients. Experimental results showed that miR-638-5p was upregulated in MDA-MB-231 treated with curcumin, while the potential target genes of miR-638-5p, CFL1, SIX4, MAZ, and CDH1 were downregulated. Mimic miR-638-5p transfection inhibited MDA-MB-231 cell proliferation and reduced migration and expression of CFL1, SIX4, and MAZ genes was decreased in mimic miR-638-5p transfected cells. Conclusion: These findings suggest that curcumin exerts its anticancer effects on MDA-MB-231 cells by modulating the expression of miR-638-5p and its possible target genes.
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BACKGROUND: Despite aggressive local and regional therapy, triple-negative breast cancer (TNBC) is characterized by an increased risk of locoregional recurrence. RNA-sequencing data has identified a large number of circRNAs in primary breast cancers, but the role of specific circRNAs in regulating the radiosensitivity of TNBC is not fully understood. This research aimed to investigate the function of circNCOR1 in the radiosensitivity of TNBC. METHODS: CircRNA high-throughput sequencing was conducted on two breast cancer MDA-MB-231 and BT549 cell lines after 6 Gy radiation. The relationship between circNCOR1, hsa-miR-638, and CDK2 was determined by RNA immunoprecipitation (RIP), FISH and luciferase assays. The proliferation and apoptosis of breast cancer cells were measured by CCK8, flow cytometry, colony formation assays, and western blot. RESULTS: Differential expression of circRNAs was closely related to the proliferation of breast cancer cells after irradiation. Overexpression of circNCOR1 facilitated the proliferation of MDA-MB-231 and BT549 cells and impaired the radiosensitivity of breast cancer cells. Additionally, circNCOR1 acted as a sponge for hsa-miR-638 to regulate the downstream target protein CDK2. Overexpression of hsa-miR-638 promoted apoptosis of breast cancer cells, while overexpression of CDK2 alleviated apoptosis and increased proliferation and clonogenicity. In vivo, overexpression of circNCOR1 partially reversed radiation-induced loosening of tumor structures and enhanced tumor cell proliferation. CONCLUSION: Our results demonstrated that circNCOR1 bounds to hsa-miR-638 and targets CDK2, thereby regulating the radiosensitivity of TNBC.
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MicroARNs , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/genética , ARN Circular/genética , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Apoptosis/genética , Movimiento Celular/genética , Quinasa 2 Dependiente de la Ciclina/genética , Quinasa 2 Dependiente de la Ciclina/metabolismoRESUMEN
BACKGROUND: Circular RNAs (circRNAs) have been implicated in the pathogenesis of atherosclerosis (AS) and the migration and proliferation of vascular smooth muscle cells (VSMCs) under oxidized low-density lipoprotein (ox-LDL). Here, we defined the exact action of human circ_0007478 in VSMC migration and proliferation induced by ox-LDL. METHODS: Human VSMCs (HVSMCs) were exposed to ox-LDL. Circ_0007478, microRNA (miR)-638, and rho-associated protein kinase 2 (ROCK2) levels were gauged by quantitative real-time PCR (qRT-PCR) and western blot. Cell viability and proliferation were assessed by MTT and EdU assays, respectively. Transwell assays were used to detect cell migration and invasion. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to evaluate the direct relationship between miR-638 and circ_0007478 or ROCK2. RESULTS: Our data indicated that circ_0007478 expression was augmented in AS serum samples and ox-LDL-treated HVSMCs. Depletion of circ_0007478 attenuated HVSMC proliferation, migration, and invasion induced by ox-LDL. Mechanistically, circ_0007478 targeted miR-638 by directly pairing to miR-638. Reduction of miR-638 reversed the effects of circ_0007478 depletion on ox-LDL-evoked proliferation, migration, and invasion in HVSMCs. ROCK2 was a direct miR-638 target and miR-638-mediated inhibition of ROCK2 relieved ox-LDL-evoked HVSMC proliferation, migration, and invasion. Furthermore, circ_0007478 was identified as a competing endogenous RNA (ceRNA) for miR-638 to modulate ROCK2 expression. CONCLUSION: Our present study establishes an undescribed ceRNA regulatory network, in which circ_0007478 targets miR-638 to upregulate ROCK2, thereby contributing to ox-LDL-induced proliferation and migration in HVSMCs.
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Aterosclerosis , MicroARNs , Humanos , Músculo Liso Vascular , Aterosclerosis/genética , Movimiento Celular , Lipoproteínas LDL/farmacología , Proliferación Celular , MicroARNs/genética , Apoptosis , Células Cultivadas , Miocitos del Músculo Liso , Quinasas Asociadas a rho/genéticaRESUMEN
BACKGROUND: There is an unmet need to improve the diagnosis of cancer with precise treatment strategies. Therefore, more powerful diagnostic, prognostic, and therapeutic biomarkers are needed to overcome tumor cells. microRNAs (miRNAs, miRs), as a class of small non-coding RNAs, play essential roles in cancer through the tumor-suppressive or oncogenic effects by post-transcriptional regulation of their targets. Many studies have provided shreds of evidence on aberrantly expressed miRNAs in numerous cancers and have shown that miRNAs could play potential roles as diagnostic, prognostic, and even therapeutic biomarkers in patients with cancers. Findings have revealed that miR-638 over or underexpression might play a critical role in cancer initiation, development, and progression. However, the mechanistic effects of miR-638 on cancer cells are still controversial. CONCLUSION: In the present review, we have focused on the diagnostic, prognostic, and therapeutic potentials of miR-638 and discussed its mechanistic roles in various types of cancers.
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MicroARNs , Neoplasias , Humanos , Biomarcadores de Tumor/genética , MicroARNs/genética , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , Regulación Neoplásica de la Expresión GénicaRESUMEN
Hsa_circRNA_0008344 (circ_0008344) is a new glioma-related circular RNA. Our study aims to explore its functions in glioma tumor progression. Real-time quantitative PCR and western blotting were used to detect RNA and protein abundances. RNase R assay, actinomycin D assay, and subcellular fractionation method were performed to identify the features of circ_0008344. Cell-counting kit-8, 5-ethynyl-2'-deoxyuridine assays, transwell assays, tube formation assay, flow cytometry, and nude mice xenograft tumor model were performed. Target relationship was predicted by bioinformatics algorithms and confirmed by dual-luciferase reporter assay. Abundances of circ_0008344 and SUZ RNA binding domain containing 1 (SZRD1) were highly elevated, while miR-638 was downregulated in glioma tumors and cells. Circ_0008344 was identified as a stable circRNA with a circular structure. Silencing circ_0008344 could restrain glioma proliferation, migration, invasion, and angiogenesis. Circ_0008344 functioned as a sponge for miR-638. The negative regulation of circ_0008344 knockdown on glioma progression and angiogenesis could be reversed by miR-638 inhibitor. SZRD1 was a target of miR-318, and its overexpression overturned the inhibition effect of miR-638 mimic on glioma progression and angiogenesis. Meanwhile, we confirmed that circ_0008344 knockdown inhibited SZRD1 expression, and its effect was reversed by miR-638 inhibitor. Also, circ_00008344 knockdown suppressed glioma tumor growth. Circ_0008344 might contribute to glioma progression through miR-638/SZRD1 axis, which might be a novel pathology and treatment target in glioma.
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Glioma , MicroARNs , ARN Circular , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Glioma/genética , Glioma/patología , Humanos , Ratones , Ratones Desnudos , MicroARNs/genética , ARN Circular/genéticaRESUMEN
Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths all over the world. Exosomes exert central roles in intercellular communication. Circular RNA Rho GTPase activating protein 10 (circARHGAP10) was related to the development of NSCLC. Nevertheless, it was unclear whether circARHGAP10 can be mediated by serum-derived exosomes in NSCLC. Materials and Methods: Protein expression of CD63, CD81, family with sequence similarity 83F (FAM83F), glucose transporter 1 (Glut1), and lactate dehydrogenase were evaluated through Western blot analysis. The expression of circARHGAP10, miR-638, and FAM83F was examined by quantitative real-time polymerase chain reaction. Cell proliferation, migration, and invasion were evaluated through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) or transwell assays. Glucose consumption and lactate production were analyzed with special commercial kits. The relationship between circARHGAP10 or FAM83F and miR-638 was identified by dual-luciferase reporter or RNA immunoprecipitation (RIP) assays. The role of circARHGAP10 in vivo was confirmed through xenograft assay. Results: circARHGAP10 was upregulated in NSCLC tissues, cells, and serum-derived exosomes. Serum-derived exosomes boosted the expression of circARHGAP10 in NSCLC cells. circARHGAP10 depletion repressed proliferation, migration, invasion, and glycolysis of NSCLC cells in vitro, and curbed tumor growth in vivo. Also, miR-638 acted as a target of circARHGAP10, miR-638 overexpression overturned circARHGAP10 upregulation-mediated acceleration of proliferation, migration, invasion, and glycolysis of NSCLC cells. Besides, miR-638 targeted FAM83F and FAM83F overexpression abolished miR-638 enhancement-mediated proliferation, migration, invasion, and glycolysis of NSCLC cells. Conclusions: Inhibition of serum-derived exosomes-mediated circARHGAP10 curbed NSCLC progression through the miR-638/FAM83F axis.
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Carcinoma de Pulmón de Células no Pequeñas , Exosomas , Neoplasias Pulmonares , MicroARNs , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Exosomas/genética , Exosomas/metabolismo , Humanos , Neoplasias Pulmonares/patología , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genéticaRESUMEN
OBJECTIVES: Ovarian cancer is one of the most fatal gynecologic malignities. miR-16-5p, miR-17-5p, and miR-638 genes were found to have been associated with ovarian cancer in accordance with the data obtained from the previous microarray research performed by Tuncer et al. (J Ovarian Res 13(1):99, 2020). The expression levels of these miRNAs in the peripheral blood samples of 142 ovarian cancer patients, and 97 healthy controls were investigated for performing the validation, and to identify whether these genes were the possible biomarkers to be used in the early diagnosis of high-risk ovarian cancer patients, and in the prognosis of patients. METHODS: The miRNA expression analysis was performed using the miRNA-specific cDNA synthesis, and real-time PCR methods following the RNA isolation from the peripheral blood lymphocytes. RESULTS: miR-16-5p, miR-17-5p, and miR-638 miRNA gene expression levels were found to have twofold higher expression levels in patient groups compared with the gene expression levels in healthy controls, and were statistically significant (p < 0.05). In addition, the comparison of the miRNA expression levels with the clinical data of patients showed that there was a significant difference with smoking history and the increased expression level of miR-17-5 (p: 0.007). There was a significant difference between the increased expression level of miR-638 with the locally advanced stage, and abdominal/pelvic metastatic patients (p: 0.03). CONCLUSIONS: The obtained data suggest that miR-16-5p, miR-17-5p, and miR-638 molecules might be the noninvasive biomarkers in identifying the ovarian cancer. However, the investigation and monitoring of the changeability of these biomarkers in benign ovarian diseases, and during the treatment must be performed in future studies for identifying the accurate diagnostic, and prognostic features of miRNAs.
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MicroARNs , Neoplasias Ováricas , Biomarcadores de Tumor/genética , Carcinoma Epitelial de Ovario/genética , Femenino , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Neoplasias Ováricas/patología , PronósticoRESUMEN
BACKGROUND: MicroRNA (miRNA) can be used as a biomarker for the early diagnosis of diabetic nephropathy (DN). The purpose of this study was to evaluate the diagnostic value of miR-638 in DN and to analyse its regulatory effect on inflammation. METHODS: This retrospective study involved 98 subjects, including non-diabetic healthy controls (n = 30), patients with type 2 diabetes (T2DM, n = 36) without complications and patients with DN (n = 32). After the anthropometric and biochemical evaluation, serum miR-638 levels were assessed by real-time reverse transcription-polymerase chain reaction (qRT-PCR). The levels of inflammatory cytokines (interleukin [IL]-1ß, IL-6, and tumor necrosis factor-alpha [TNF-α]) were detected using enzyme-linked immunosorbent assay. The Spearman correlations were used to analyze the correlation between miR-638 and urinary albumin excretion (UAE), estimated glomerular filtration rate (eGFR), and inflammatory factors. Furthermore, the receiver operating characteristic (ROC) curve was used to measure the diagnostic value of miR-638 in DN. Human mesangial cells (HMCs) were treated with normal glucose (NG, 5.5 mM glucose), high glucose (HG, 30 mM glucose), or high osmotic pressure solution (HO, 5.5 mM glucose + 24.5 mM mannitol) in vitro to simulate the hyperglycamic state in vivo. Subsequently, the HMCs were transfected with miR-638 mimics to regulate the level of miR-638 in the cells and detect its regulation on cell inflammation and proliferation. RESULTS: Compared with healthy controls and patients with T2DM, serum miR-638 in patients with DN was significantly lower. The reduced miR-638 expression has a significant diagnostic value, which can significantly distinguish patients with DN from healthy controls or patients with T2DM. Inflammatory factors were significantly upregulated in patients with DN and negatively correlated with miR-638 levels. In addition, miR-638 was negatively correlated with UAE and positively correlated with eGFR. HG decreased the level of miR-638 and promoted the expression of inflammatory factors and proliferation in HMCs. However, miR-638 mimic significantly decreased the levels of inflammatory factors and inhibited the proliferative ability induced by HG. CONCLUSIONS: Serum miR-638 expression was low in DN and can be a potentially valuable biomarker for DN. This miRNA seems to influence inflammatory responses and participate in the progression of DN by regulating proliferation.
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Our previous study observed that circular RNA protein tyrosine kinase 2 (circ-PTK2) was upregulated and correlated with worse clinical features and unfavorable prognosis in multiple myeloma (MM) patients. Thus, this study aimed to further characterize the regulatory function of circ-PTK2 on cell malignant activities and its target microRNA-638 (miR-638) as well as downstream MEK/ERK, WNT/ß-catenin signaling pathways in MM. The effect of circ-PTK2 on MM cell proliferation, apoptosis, migration, invasion and its potential target miRNAs was assessed by transfecting circ-PTK2 overexpression plasmids into U226 cells and circ-PTK2 knock-down plasmids into LP-1 cells. Furthermore, the interaction between circ-PTK2 and miR-638 mediated MEK/ERK and WNT/ß-catenin signaling pathways was validated by rescue experiments. Circ-PTK2 was overexpressed in most MM cell lines compared to normal plasma cells. Overexpressing circ-PTK2 promoted proliferation and migration, inhibited apoptosis in U266 cells, but did not affect cell invasion; knocking down circ-PTK2 achieved opposite effect in LP-1 cells. Besides, circ-PTK2 reversely regulated miR-638 expression but not miR-4690, miR-6724, miR-6749 or miR-6775. The following luciferase reporter assay illustrated the direct bind of circ-PTK2 towards miR-638. In rescue experiments, overexpressing miR-638 suppressed proliferation, migration, while promoted apoptosis in both wild U266 cells and circ-PTK2-overexpressed U266 cells; meanwhile, overexpressing miR-638 also suppressed MEK/ERK and WNT/ß-catenin pathways in both wild U266 cells and circ-PTK2-overexpressed U266 cells. Knocking down miR-638 achieved opposite effect in both wild LP-1 cells and circ-PTK2-knocked-down LP-1 cells. In conclusion, circ-PTK2 promotes cell proliferation, migration, suppresses cell apoptosis via miR-638 mediated MEK&ERK and WNT&ß-catenin signaling pathways in MM.
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BACKGROUND: Previous studies had shown that microRNA-638 (miR-638) exhibited different effects in malignant tumors. Moreover, the function of miR-638 has not been reported in breast cancer. Hence, we designed this research to explore the function of miR-638 in breast cancer. METHODS: Firstly, miR-638 expressions were measured in breast cancer tissues via RT-qPCR. Protein expressions were detected through immunocytochemical (IHC) assay and western blot analysis. Then, Cell Counting Kit-8 (CCK-8) assay and Transwell assay were conducted to observe proliferation and motility of the cells. Dual luciferase assay was performed to confirm the binding site between miR-638 and Homeobox protein Hox-A9 (HOXA9). RESULTS: Reduced expression of miR-638 was detected in breast cancer. And low miR-638 expression was related to poor prognosis in patients with breast cancer. Functionally, the viability, migration, and invasion of the breast cancer cells were suppressed by miR-638 overexpression. Furthermore, miR-638 can directly bind to HOXA9, and increased expression of HOXA9 was also detected in breast cancer. In particular, HOXA9 upregulation can impair anti-tumor effect of miR-638 in breast cancer, and miR-638 can hinder the Wnt/ß-cadherin pathway and epithelial-mesenchymal transition (EMT) in breast cancer. CONCLUSION: miR-638 inhibits breast cancer progression through binding to HOXA9.
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Neoplasias de la Mama , Proteínas de Homeodominio , MicroARNs , Neoplasias de la Mama/genética , Cadherinas/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Proteínas de Homeodominio/genética , Humanos , MicroARNs/genética , PronósticoRESUMEN
BACKGROUND: Propofol has recently been attracted increasing attention for its anti-tumor property in cancers, including colorectal cancer (CRC). However, the anti-tumor molecular determinants of propofol largely remain to be elucidated. METHODS: The levels of circRNA poly(A) binding protein nuclear 1 (circ-PABPN1, hsa_circ_0031288), microRNA (miRNA)-638 and serine and arginine-rich factor 1 (SRSF1) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell viability, colony formation, apoptosis, invasion, and migration were detected by the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, transwell, and wound-healing assays, respectively. Animal studies were used to evaluate the biological action of circ-PABPN1 in the propofol-mediated anti-CRC effect. Targeted relationships among circ-PABPN1, miR-638 and SRSF1 were validated by dual-luciferase reporter assays. RESULTS: Our data showed the anti-tumor activity of propofol in CRC, as evidenced by the repression in cell viability, colony formation, invasion, migration and the promotion in cell apoptosis in vitro, as well as the suppression in tumor growth in vivo. Circ-PABPN1 was overexpressed in CRC tissues and cells, and propofol down-regulated circ-PABPN1 in a dose-dependent manner. Moreover, circ-PABPN1 was a functional effector of propofol in suppressing CRC development in vitro and in vivo. Circ-PABPN1 directly targeted miR-638, and SRSF1 was a direct target of miR-638. Propofol repressed CRC development in vitro by up-regulating miR-638 or down-regulating SRSF1. Furthermore, propofol regulated SRSF1 expression by the circ-PABPN1/miR-638 axis in CRC cells. CONCLUSION: Our current findings identified the circ-PABPN1/miR-638/SRSF1 axis as a novel anti-tumor mechanism of propofol in CRC, providing a new rationale for developing propofol as a promising therapeutic agent for CRC.
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Antineoplásicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Propofol/farmacología , ARN Circular/genética , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ratones Endogámicos BALB C , MicroARNs/genética , Proteína I de Unión a Poli(A)/genética , Factores de Empalme Serina-Arginina/genética , Factores de Empalme Serina-Arginina/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: The application of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) requires customized materials to target disease or cell damage. We hypothesized that EVs exert different inflammatory effects on one recipient cell, although stem cells of different origins in humans have similar payloads. RESULTS: Here, the payload of EVs released by crosstalk between MSCs and human middle ear epithelial cells (HMEECs) extracted from adipose tissue, bone marrow and tonsils significantly increased the level of anti-inflammatory factors. EVs derived from the co-culture medium decreased TNF-α, COX-2, IL-1ß, and IL-6 levels to approximately zero within 3 h in HMEECs. Expression of miR-638 and amyloid-ß A4 precursor protein-binding family A member 2 was analyzed using microarrays and gene ontology analysis, respectively. CONCLUSIONS: In conclusion, stem cells of different origins have different payloads through crosstalk with recipient-specific cells. Inducing specific factors in EVs by co-culture with MSCs could be valuable in regenerative medicine.
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Vesículas Extracelulares/metabolismo , Células Madre Mesenquimatosas/citología , Tejido Adiposo , Médula Ósea/metabolismo , Supervivencia Celular , Células Cultivadas , Técnicas de Cocultivo , Células Epiteliales , Humanos , Interleucina-1 , Interleucina-1beta , Interleucina-6 , MicroARNs , Tonsila Palatina/metabolismoRESUMEN
MicroRNA (miRNA) is a form of short, single-stranded and non-coding RNA that is important in regulating the post-transcriptional modification of multiple downstream targets. Many miRNAs have been reported to involve in controlling the progression of human diseases, and one of them is miR-638, which play essential roles in regulating the development of human cancer. By targeting the 3'-ends of its targets, miR-638 can regulate cellular processes including proliferation, invasion, metastases, angiogenesis, apoptosis and inflammation. This review was aimed to summarize current findings on the roles of miR-638 in different human cancers based on the results from various in vitro, in vivo and clinical studies. The biogenesis process and tissue expression, followed by the roles of miR-638 in regulating the development of various human cancers by targeting different downstream targets were covered in this review. The potential applications and challenges of employing miR-638 as cancer biomarker and therapeutic agent were also discussed.
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Biomarcadores de Tumor/genética , MicroARNs/genética , Neoplasias/genética , Animales , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/terapia , Pronóstico , Transducción de SeñalRESUMEN
Objective: Low plasma level of high-density lipoprotein cholesterol (HDL-C) associated with poor outcomes in several cardiovascular diseases, including pulmonary arterial hypertension (PAH). Regulation of miR-638 have been proved to be associated with PAH. The aim of this study was to evaluate the expression of miR-638 after Xuezhikang (XZK) therapy in patients with low HDL-C. Methods: Plasma levels of miR-638 were quantified by real-time polymerase chain reactions in 20 patients with PAH and 30 healthy controls. A total of 40 subjects with low HDL-C were assigned to receive an XZK therapy for 6 months. The miR-638 expression profiles were detected in PAH patients, XZK-treated subjects and lovastatin treated pulmonary arterial smooth muscle cells (PA-SMCs). Results: The relative expression level of miR-638 in the plasma was lower in the PAH patients than that in the controls (p < 0.001). An increase of 11.2% from baseline in the HDL-C level was found after XZK therapy (p < 0.001). The relative expression of miR-638 was increased after XZK treatment (p < 0.01). The changes of miR-638 were inversely associated with baseline HDL-C levels. A significantly reduction in miR-638 expression were found in PDGF-BB-treated hPA-SMCs compared to the control cells, and the pre-treatment of the cells with lovastatin significantly re-gain the expression levels in miR-638. Conclusion: In patients with low HDL-C levels, XZK therapy raised the expression of miR-638, suggesting that the potential therapeutic effect of XZK in PAH patients with low serum HDL-C levels deserves further exploration.
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Accumulating studies suggest that circular RNAs (circRNAs) function as key regulators in human cancers. We found that hsa_circ_0001869 participated in non-small cell lung cancer (NSCLC) progression. However, its expression and function during NSCLC remain unknown. The data advised that hsa_circ_0001869 expression was increased in NSCLC cell lines and tissues. High hsa_circ_0001869 expression had negatively correlation with the NSCLC patients prognosis. Bioinformatics and luciferase report analyses confirmed that miR-638 and FOSL2 were hsa_circ_0001869 downstream target. hsa_circ_0001869 downregulation decreased tumor proliferation, invasion and migration by promoting miR-638 expression and decreasing FOSL2 expression. As a result of overexpression of FOSL2 or silencing of miR-638, the recovery of proliferation, migration, and invasion after hsa_circ_0001869 silencing. Overexpression of FOSL2 also led to recovery of migration, invasion and proliferation after upregulation of miR-638. In vivo studies confirmed that overexpression of FOSL2 or silencing of miR-638 led to the recovery of tumor growth ability regarding A549 cells after hsa_circ_0001869 knockdown. Present investigation discovered that hsa_circ_0001869 enhanced NSCLC progression via sponging miR-638 and promoting FOSL2 expression. hsa_circ_0001869 downregulation suppressed tumor growth and invasion ability.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Antígeno 2 Relacionado con Fos/metabolismo , Neoplasias Pulmonares/metabolismo , MicroARNs/metabolismo , ARN Circular/metabolismo , Células A549 , Animales , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Movimiento Celular , Proliferación Celular , Biología Computacional , Bases de Datos Genéticas , Progresión de la Enfermedad , Femenino , Antígeno 2 Relacionado con Fos/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Persona de Mediana Edad , Invasividad Neoplásica , ARN Circular/genética , Transducción de Señal , Carga TumoralRESUMEN
OBJECTIVE: The aim of this study was to investigate the function and prognostic value of miR-638 in renal cell carcinoma (RCC). METHODS: Expression of miR-638 in RCC tissues and corresponding noncancerous tissues were examined by reverse transcription quantitative polymerase chain reaction (RT-qPCR). To explore the effects of miR-638 on cell migration, invasion, viability, and apoptosis of RCC cells, wound scratch, transwell, MTT, CCK-8, and flow cytometry assays were performed. Kaplan-Meier and Cox regression analyses were used to evaluate the relationship between miR-638 expression and prognosis of RCC patients. Potential target genes of miR-638 were predicted and validated via multiple bioinformatics analyses. RESULTS: miR-638 was upregulated in RCC tissues when compared with corresponding noncancerous tissues (P < 0.05). Upregulation of miR-638 expression by transfection with a synthetic miR-638 mimic promoted cell migration, invasion, and viability and suppressed cell apoptosis. Moreover, Kaplan-Meier analysis revealed that upregulation of miR-638 associated with shorter overall survival (OS; P = 0.001). Cox univariate and multivariate regression analysis suggested that miR-638 expression is an independent predictive factor for the prognosis of RCC patients (P = 0.004). KCNQ1, DNAJC6, and PNP were identified as potential target genes of miR-638. CONCLUSIONS: The results of this study demonstrated that miR-638 functions as an oncogene in RCC and has the potential to be a prognostic biomarker for RCC.
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PURPOSE: Exosomal microRNAs (miRNAs) play essential roles in the development of hepatocellular carcinoma (HCC). Nevertheless, the role and mechanism of exosomal miR-638 in HCC development remain largely unknown. METHODS: Exosomes were isolated and confirmed via transmission electron microscopy and western blot. The abundances of miR-638 and specificity protein 1 (SP1) were measured via quantitative reverse transcription polymerase chain reaction or western blot. Cell proliferation was investigated by Cell Counting Kit-8, colony formation assay, apoptosis, cell cycle distribution and related protein expression. Cell migration and invasion were detected via transwell assay and western blot. Co-culture experiment was performed to assess exosome transfer from HCC cells to endothelial cells. The target correlation between miR-638 and SP1 was analyzed via dual-luciferase reporter and RNA immunoprecipitation assays. The subcutaneous xenograft experiment was conducted to test the function of miR-638 in vivo. RESULTS: The miR-638 level declined in exosomes from serum or HCC cell medium. miR-638 overexpression repressed HCC cell proliferation by decreasing viability and colony formation and inducing apoptosis and cell cycle arrest at G1 phase, and decreased abilities of migration and invasion. Exosomal miR-638 from HCC cells could transfer to human umbilical vein endothelial cells (HUVECs) and suppress HUVEC proliferation, migration and invasion. SP1 was a target of miR-638 and overexpression of SP1 reversed the effect of miR-638 on HCC cells. Overexpression of miR-638 reduced xenograft tumor growth via decreasing SP1. CONCLUSION: Exosomal miR-638 inhibited HCC tumorigenesis by targeting SP1. This study indicated the potential clinical implications of miR-638 in HCC.
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BACKGROUND: MicroRNA (miRNA) expression has been implicated in leukaemia. In recent years, miRNAs have been under investigation for their potential as non-invasive biomarkers in acute promyelocytic leukaemia (APL). We investigated whether miR-638 in circulating leukaemia cells is a non-invasive biomarker in diagnosis, assessment of the treatment response and minimal residual disease (MRD) surveillance of APL. METHODS: Sixty cases of acute myeloid leukaemia (AML), including 30 cases of APL and 30 cases of non-APL AML, were selected. Thirty healthy controls were also selected. Bone marrow (BM) and peripheral blood (PB) samples were collected from APL patients at diagnosis and post-induction. Microarray analysis and quantitative real-time PCR (qRT-PCR) were performed for miRNA profiling and miR-638 expression analysis, respectively. For statistical analysis, Mann-Whitney U test, Wilcoxon Signed Rank test, receiver operating characteristic (ROC) curve analysis and Spearman's rho correlation test were used. RESULTS: Both microarray and qRT-PCR data showed that miR-638 was significantly upregulated in BM after APL patients received induction therapy. Moreover, miR-638, which is specifically downregulated in APL cell lines, was upregulated after all-trans retinoic acid (ATRA)-induced myeloid differentiation. Receiver operating characteristic (ROC) curve analyses revealed that miR-638 could serve as a valuable biomarker for differentiating APL from controls or non-APL AML. Furthermore, miR-638 expression was sharply increased after induction therapy and complete remission (CR). An inverse correlation was observed between miR-638 and PML-RARα transcripts levels in BM samples, while a positive correlation was revealed between PB miR-638 and BM miR-638 levels in APL patients after induction therapy. CONCLUSIONS: Our study suggested that miR-638 may serve as a potential APL biomarker for diagnosis and assessment of the response to targeted therapy, and PB miR-638 could be used for non-invasive MRD surveillance in APL.
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Leucemia Mieloide Aguda/sangre , Leucemia Promielocítica Aguda/sangre , MicroARNs/sangre , Neoplasia Residual/sangre , Biomarcadores de Tumor/sangre , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Femenino , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Leucemia Promielocítica Aguda/genética , Masculino , MicroARNs/genética , Persona de Mediana Edad , Neoplasia Residual/genética , Neoplasia Residual/patología , Células Neoplásicas Circulantes/metabolismo , Inducción de Remisión , Tretinoina/administración & dosificación , Tretinoina/efectos adversosRESUMEN
Long noncoding RNAs (lncRNAs) have been validated to mediate the development of atherosclerosis (AS). In the present study, the molecular mechanisms and functions of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in the advancement of human aortic endothelial cells (HAECs) were investigated. The levels of lncRNANEAT1 and miR638 expression in clinical samples and cells were explored via quantitative reverse transcription polymerase chain reaction. Colony formation and CCK8 assays were performed to determine the proliferative capacity of cells, and the apoptotic capacity of cells was analyzed on the basis of apoptotic cell proportion and caspase3 activity. Then, the proportion of cells and correlations among phosphoglycerate kinase 1 (PGK1), NEAT1, and miR638 were determined through RNA immunoprecipitation and luciferase assays and bioinformatics analysis. Moreover, the expression levels of Ki67, proliferating cell nuclear antigen, PGK1, Bax, Bcl2, (p)mTOR, (p)AKT, and ßcatenin were analyzed via western blot analysis. In the serum of patients with AS and HAECs induced by oxidized lowdensity lipoprotein (oxLDL), the expression level of miR638 was decreased, whereas that of NEAT1 was increased. After oxLDL therapy, NEAT1 knockdown suppressed HAEC proliferation and stimulated HAEC apoptosis, which could be reversed by the miR638 inhibitor. NEAT1 inhibited miR638 expression through direct mutual action. The following mechanical investigations revealed that PGK1 was a miR638 target, whose expression was increased by NEAT1, a competing endogenous RNA of miR638. Additionally, the miR638 inhibitor contributed to proliferation and suppressed apoptosis through the activation of the AKT/mTOR signaling pathway in oxLDLinduced HAECs. NEAT1 adjusted the AKT/mTOR signaling pathway via miR638 in oxLDLinduced HAECs to accelerate their proliferation and impede their apoptosis. This result revealed that NEAT1 may be valuable in the treatment of AS.