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Background: The objective was to elucidate the potential epigenetic regulatory mechanism in HMOX1 expression in preeclampsia. Materials & methods: HMOX1 promoter DNA methylation was evaluated in the placental tissue and blood of preeclamptic and normotensive pregnant women. HMOX1 and miR-153-3p gene expression were assessed in placental tissue and peripheral blood mononuclear cells (PBMCs). Related microarray datasets in the Gene Expression Omnibus database were also analyzed. Results: In placental tissue, despite HMOX1 expression downregulation, there was no significant change in HMOX1 methylation. In PBMCs, there was no significant alteration in HMOX1 expression, while hypomethylation was observed in blood. The miR-153-3p expression increased in the placental tissue and in the PBMCs of preeclampsia. Conclusion: DNA methylation does not affect HMOX1 expression, while miR-153-3p might be a biomarker for preeclampsia.

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BACKGROUND: To explore the role and mechanism of triptolide in regulating esophageal squamous cell carcinoma (ESCC) progression by mediating the circular RNA (circRNA)-related pathway. METHODS: The expression levels of circNOX4, miR-153-3p and special AT-rich sequence binding protein-1 (SATB1) were measured by qRT-PCR. Cell proliferation was confirmed by cell counting kit-8 assay and colony formation assay. Flow cytometry was employed to measure cell apoptosis and cell cycle process. Moreover, cell migration and invasion were detected using transwell assay. The protein levels of epithelial-mesenchymal transformation markers and SATB1 were determined by western blot analysis. Furthermore, dual-luciferase reporter assay and RIP assay were performed to confirm the interaction between miR-153-3p and circNOX4 or SATB1. Xenograft tumor models were built to verify the effects of triptolide and circNOX4 on ESCC tumor growth. RESULTS: CircNOX4 was highly expressed in ESCC tissues and cells, and its expression could be reduced by triptolide. Triptolide could inhibit ESCC proliferation, cell cycle process, migration, invasion, EMT process, and promote apoptosis, while these effects were reversed by circNOX4 overexpression. MiR-153-3p could be sponged by circNOX4, and the promotion effect of circNOX4 on the progression of triptolide-treated ESCC cells was abolished by miR-153-3p overexpression. SATB1 was a target of miR-153-3p. Also, SATB1 knockdown reversed the enhancing effect of miR-153-3p inhibitor on the progression of triptolide-treated ESCC cells. Triptolide reduced ESCC tumor growth by regulating the circNOX4/miR-153-3p/SATB1 axis. CONCLUSION: Triptolide could hinder ESCC progression, which was mainly achieved by regulating the circNOX4/miR-153-3p/SATB1 axis.

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Circular RNAs are vital players in tumorigenesis. We held the purpose to investigate the role and mechanism of circ_0103809 in non-small cell lung cancer (NSCLC). The expressions of circ_0103809, miR-153-3p and HDAC1 mRNA were determined using quantitative real-time PCR assay, and HDAC1 protein was quantified using western blot analysis. MTT, EdU, flow cytometry, tube-formation, wound healing and tube-formation assays were conducted for functional analysis. The predicted relationship among circ_0103809, miR-153-3p and HDAC1 was ascertained using dual-luciferase analysis, RIP assay and pull-down analysis. Animal models were further constructed to realize circ_0103809's role in vivo. Circ_0103809 was upregulated NSCLC specimens, cells and serum-derived exosomes. Serum exosomal circ_0103809 had the potency to be a diagnostic biomarker for NSCLC. Circ_0103809 silencing inhibited NSCLC cell growth, metastasis and angiogenesis and triggered cell cycle arrest and apoptosis. Circ_0103809 deficiency also suppressed the growth of transplanted tumors. Circ_0103809 acted as the miR-153-3p sponge, and the biological effects of circ_0103809 knockdown were relieved by miR-153-3p inhibition. HDAC1 was directly targeted by miR-153-3p, and miR-153-3p enrichment inhibited NSCLC cell malignant phenotypes by sequestering HDAC1. Circ_0103809 knockdown repressed NSCLC malignant progression partly by regulating miR-153-3p/HDAC1 signaling.

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The early stages of ageing are a critical time window in which the ability to detect and identify precocious molecular and cognitive markers can make the difference in determining a healthy vs unhealthy course of ageing. Using the 6-different object task (6-DOT), a highly demanding hippocampal-dependent recognition memory task, we classified a population of middle-aged (12-month-old) CD1 male mice in Impaired and Unimpaired based on their short-term memory. This approach led us to identify a different microRNAs expression profile in the hippocampus of Impaired mice compared to Unimpaired ones. Among the dysregulated microRNAs, miR-153-3p was upregulated in the hippocampus of Impaired mice and appeared of high interest for its putative target genes and their possible implication in memory-related synaptic plasticity. We showed that intra-hippocampal injection of the miR-153-3p mimic in adult (3-month-old) mice is sufficient to induce a short-term memory deficit similar to that observed in middle-aged Impaired mice. Overall, these findings unravel a novel role for hippocampal miR-153-3p in modulating short-term memory that could be exploited to prevent early cognitive deficits in ageing.

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Ischaemic stroke is a common cerebrovascular disease. Long non-coding RNA (lncRNA) of small nucleolar RNA host gene (SNHG15) has been supposedly performed a regulatory role in many diseases. Nonetheless, the function of SNHG15 in cerebral ischaemia-reperfusion injury has not been clarified. The OGD/R of Neuro2A cells simulated the ischaemic and reperfused states of the brain. Neuro2a cell line with stable transfection of plasmid with silent expression of SNHG15 was constructed. Neuro2a cell lines transfected with miR-153-3p mimic (miR-153-3p-mimics) and miR-153-3p inhibitor (miR-153-3p-inhibition) were constructed. Expression of SNHG15, mi R-200a, FOXO3 and ATG7 in mouse brain tissue and N2a cells was identified by qRT-PCR. Western blot (WB) analysis of mouse brain tissue and Neuro2a cells revealed the presence of the proteins ATG5, Cle-caspase-3, Bax, Bcl-2, LC3 II/I and P62 (WB). The representation and distribution of LC3B were observed by immunofluorescence. The death of cells was measured using a technique called flow cytometry (FACS). SNHG15 was highly expressed in cerebral ischaemia-reperfusion injury model. Down-regulation of SNHG15 lead to lower apoptosis rate and decreased autophagy. Dual luciferase assay and co-immunoprecipitation (CoIP) found lncRNA SNHG15/miR-153-3p/ATG5. Compared to cells transfected with NC suppression, cells transfected with miR-153-3p-inhibition had substantially greater overexpression of LC 3 II/I, ATG5, cle-Caspase-3, and Bax, as determined by a recovery experiment, the apoptosis rate was elevated, yet both P62 and Bcl-2 were significantly lower and LC3+ puncta per cells were significantly increased. Co-transfection of miR-153-3p-inhibition and sh-SNHG15 could reverse these results. LncRNA SNHG15 regulated autophagy and prevented cerebral ischaemia-reperfusion injury through mediating the miR-153-3p/ATG5 axis.

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Alzheimer's disease is the most frequent neurodegenerative disease and is characterized by progressive cognitive impairment and decline. NSCs (neural stem cells) serve as beneficial and promising adjuncts to treat Alzheimer's disease. This study aimed to determine the role of miR-153-3p expression in NSC differentiation and proliferation. We illustrated that miR-153-3p was decreased and GPR55 was upregulated during NSC differentiation. IL-1ß can induce miR-153-3p expression. Luciferase reporter analysis noted that elevated expression of miR-153-3p significantly inhibited the luciferase value of the WT reporter plasmid but did not change the luciferase value of the mut reporter plasmid. Ectopic miR-153-3p expression suppressed GPR55 expression in NSCs and identified GPR55 as a direct target gene of miR-153-3p. Ectopic expression of miR-153-3p inhibited NSC growth and differentiation into astrocytes and neurons. Elevated expression of miR-153-3p induced the release of proinflammatory cytokines, such as TNF-α, IL-1ß and IL-6, in NSCs. Furthermore, miR-153-3p inhibited NSC differentiation and proliferation by targeting GPR55 expression. These data suggested that miR-153-3p may act as a clinical target for the therapeutics of neurodegenerative diseases.

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BACKGROUND: Lupus nephritis (LN) is one of the most common and serious complications of systemic lupus erythematosus. Our experiments aimed to evaluate the molecular mechanisms of long noncoding RNA (lncRNA) TUG1 in a human renal mesangial cell (HRMC) model of LN. METHODS: Cells were treated with lipopolysaccharide (LPS) to induce inflammatory damage. StarBase, TargetScan, and a luciferase reporter assay were used to predict and confirm the interactions between lncRNA TUG1, miR-153-3p, and Bcl-2. We determined the lncRNA TUG1 and miR-153-3p levels in LPS-induced HRMCs using quantitative reverse transcription PCR (RT-qPCR). MTT and flow cytometry analyses were used to detect HRMC proliferation and apoptosis, respectively. In addition, the expression of the apoptosis-related proteins Bax and Bcl-2 was evaluated using western blot analysis and RT-qPCR. Lastly, the secretion of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) was assessed using ELISA. RESULTS: miR-153-3p directly targeted lncRNA TUG1. The level of lncRNA TUG1 was remarkably lower and miR-153-3p expression was markedly higher in LPS-treated HRMCs than in untreated cells. Transfection with TUG1-plasmid relieved LPS-induced HRMC injury, as evidenced by increased cell viability, inhibited apoptotic cells, reduced Bax expression, increased Bcl-2 level, and reduced secretion of inflammatory cytokines. Importantly, these findings were reversed by miR-153-3p mimic. We also found that miR-153-3p directly targeted Bcl-2 and negatively regulated Bcl-2 expression in HRMCs. In addition, our findings suggest that miR-153-3p inhibitor relieved LPS-induced HRMC injury via the upregulation of Bcl-2. CONCLUSION: lncRNA TUG1 alleviated LPS-induced HRMC injury through regulation of the miR-153-3p/Bcl-2 axis in LN.

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Breast cancer is considered the solid tumor most sensitive to chemotherapy. However, it can become resistant to various chemotherapeutic drugs, including doxorubicin, which triggers cell death by intercalation between DNA bases, free radical formation, and topoisomerase II inhibition. When drug resistance develops, several miRNAs are dysregulated, suggesting that miRNAs may play a significant role in resistance formation. In the current study, we investigated how doxorubicin sensitivity of breast cancer cells is affected by miR-153-3p and its target gene. The MTT method was used to determine the chemo-sensitizing effect of miR-153-3p on doxorubicin in MCF-7 and MDA-MB-231 cell lines. Results of Western blot and dual luciferase confirmed that miR-153-3p targets KIF20A and decreases its expression. Transwell and flow cytometry experiments showed that miR-153-3p and doxorubicin together had higher effects on MCF-7 and MDA-MB-231 cell proliferation, migration, and invasion, as well as increasing apoptosis and arresting cells in the G1 phase. Proteins related to apoptosis and the cell cycle exhibited the same tendency. Intracellular vesicle formation was inhibited and RAB26 was also downregulated by treatment with miR-153-3p alone or in combination with doxorubicin. Doxorubicin's ability to suppress tumors may be enhanced by miR-153-3p, according to in vivo studies. According to our findings, miR-153-3p has a direct effect on KIF20A and may regulate the formation of intracellular vesicles, which in turn makes breast cancer cells more susceptible to doxorubicin.

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This study aimed to explore the role of LncKCNQ1OT1/hsa-miR-153-3p/RUNX2 in the odontoblastic differentiation of human dental pulp stem cells (DPSCs) and its possible mechanism. The expression of LncKCNQ1OT1, hsa-miR-153-3p, and RUNX2 in the odontoblastic differentiation was detected by qRT-PCR. Interaction between LncKCNQ1OT1 and hsa-miR-153-3p and interaction between hsa-miR-153-3p and RUNX2 were detected by dual-luciferase assay. The cell viability of DPSCs was detected by CCK-8, and the effect of LncKCNQ1OT1 and hsa-miR-153-3p on the odontoblastic differentiation of DPSCs was observed by alizarin red staining, alkaline phosphatase (ALP) activity assay, and Western blot for RUNX2, DSPP, and DMP-1. The results showed, during odontoblastic differentiation of DPSCs, the expression of LncKCNQ1OT1 increased, hsa-miR-153-3p expression decreased, and RUNX2 expression increased. Dual-luciferase assay showed that LncKCNQ1OT1 sponges hsa-miR-153-3p and hsa-miR-153-3p targets on RUNX2. After LncKCNQ1OT1 and hsa-miR-153-3p expressions of DPSCs were changed, the cell viability was not notably changed, but the odontoblastic differentiation was notably changed, which was confirmed with Alizarin Red staining, ALP activity, and Western blot for RUNX2, DSPP, and DMP-1. The results indicate that LncKCNQ1OT1 promotes the odontoblastic differentiation of DPSCs via regulating hsa-miR-153-3p/RUNX2 axis, which may provide a therapeutic clue for odontogenesis.

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Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous and aggressive tumor with high mortality and unfavorable prognosis. Numerous long non-coding RNAs (lncRNAs) have been confirmed to exert pivotal parts in cancers. Nevertheless, the functions of most lncRNAs in HNSCC need deeper exploration. Our present research tried to clarify the biological role of TM4SF19 antisense RNA 1 (TM4SF19-AS1) and investigate its regulatory mechanism in HNSCC. RT-qPCR analysis was done to test TM4SF19-AS1 expression and identify the up-regulation of TM4SF19-AS1 in HNSCC cells. Loss-of-function assays were also involved, and the data implied that TM4SF19-AS1 knockdown hampered the proliferation, migration, invasion, along with epithelial-mesenchymal transition (EMT) of HNSCC cells. In vivo assays revealed TM4SF19-AS1 depletion restrained HNSCC tumor growth. Additionally, mechanism experiments were implemented to uncover the underlying regulatory mechanism of TM4SF19-AS1 in HNSCC cells. It turned out that TM4SF19-AS1 modulated laminin subunit gamma 1 (LAMC1) expression via sequestering microRNA-153-3p (miR-153-3p) and recruiting heterogeneous nuclear ribonucleoprotein C (HNRNPC) protein. Rescue assays confirmed that TM4SF19-AS1 contributed to HNSCC cell malignant behaviors via up-regulating LAMC1. To summarize, TM4SF19-AS1 played an oncogenic role in HNSCC cells, signifying TM4SF19-AS1 may have the potential to be used as a novel molecular target for HNSCC diagnosis.

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To study the effect of miR-153-3p on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in a high glucose environment and its potential mechanism. The results showed that high glucose inhibited the osteogenic differentiation of BMSCs, and the expression of miR-153-3p increased during osteogenic differentiation. Further experiments found that in BMSCs induced by high glucose, overexpression of miR-153-3p inhibited the osteogenic differentiation of BMSCs, and the expressions of osteogenesis-related genes bone sialoprotein, Collagen I and alkaline phosphatase were down-regulated, while silencing of miR-153-3p alleviated the inhibition effect. The dual-luciferase reporter gene assay confirmed that the 3'-untranslated region (3'-UTR) of runt related transcription factor 2 (RUNX2) had a targeted binding site with miR-153-3p and a negative regulatory effect. Molecular studies further confirmed that miR-153-3p inhibited the osteogenic differentiation of BMSCs by targeting the 3'-UTR of RUNX2. In conclusion, our study found that as one key regulator of high glucose affecting the osteogenic differentiation of BMSCs, miR-153-3p may play a negative regulatory role by inhibiting the expression of RUNX2.

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Oral squamous cell carcinoma (OSCC) is a common cancer with high recurrence, metastasis rates and poor prognosis. Circular RNAs (circRNAs) take part in regulating OSCC. Herein, we examined the role of circ_0008068 in OSCC. The circ_0008068, Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1) mRNA, microRNA-153-3p (miR-153-3p) and acylgycerol kinase (AGK) contents were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Moreover, in vitro and in vivo assays were conducted to scrutinize the effects of circ_0008068 on OSCC. Additionally, the contact between miR-153-3p and circ_0008068 or AGK was assessed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Thereafter, we found that the appearance of circ_0008068 and AGK was increased, and miR-153-3p content was diminished in OSCC. Circ_0008068 lack subdued cell proliferation, migration, invasion, tube formation and glycolysis metabolism, but stimulated cell apoptosis in OSCC. In addition, circ_0008068 bound to miR-153-3p to modulate the expression of its target AGK. Besides, miR-153-3p was validated to act as a tumor suppressor in OSCC tumorigenesis by suppressing AGK. Additionally, circ_0008068 knockdown also attenuated tumor growth in nude mice. In all, circ_0008068 expedited the growth of OSCC by miR-153-3p/AGK axis.Abbreviations: OSCC: Oral squamous cell carcinoma; AGK: Acylgycerol kinase; CircRNA: Circular RNA; KATNAL1: Katanin p60 ATPase-containing subunit A-like 1; qRT-PCR: Quantitative real-time polymerase chain reaction; miRNAs/miRs: MicroRNAs; RIP: RNA immunoprecipitation; 3'UTR3': -untranslated region; HK2: Hexokinase 2; LDHA Lactate dehydrogenase A; IHC: Immunohistochemistry; CCK8: Cell counting kit-8; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase.

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Dental pulp stem cells (DPSCs) have multilineage differentiation potential and especially show a great foreground in bone regeneration engineering. The mechanism of osteogenic differentiation of DPSCs needs to be explored exactly. As a kind of endogenous and non-coding small RNAs, microRNAs (miRNAs) play an important role in many biological processes including osteogenic differentiation. However, the mechanism of miR-153-3p in osteogenic differentiation of DPSCs is still unknown. Core-binding factors-beta (CBFß) is a non-DNA-binding factor that combines with the runt-related transcription factor family transcription factors to mediate their DNA-binding affinities, and plays a critical role in regulating osteogenic differentiation. In this study, we explored the mechanisms of miR-153-3p and CBFß in DPSC osteogenesis. The expression of miR-153-3p and CBFß was tested under the osteogenic condition, and the influence led by changing the expression of miR-153-3p or CBFß had also been detected. A luciferase reporter assay confirmed that miR-153-3p directly targeted to CBFß. The osteogenic markers, alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and bone morphogenetic protein 2 (BMP2), were tested in protein level or mRNA level. ALP and Alizarin red staining were used to detect the osteoblast activity and mineral deposition. In osteogenic condition, the expressions of CBFß and osteogenic markers were upregulated, whereas that of miR-153-3p was downregulated. miR-153-3p negatively regulated the osteogenic differentiation, and overexpression of CBFß could offset the negative effect of miR-153-3p. Our findings provided a novel strategy for DPSC application in treatment of bone deficiencies and facilitated bone regeneration.

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INTRODUCTION: This study aims to explore the effect and related molecular mechanism of miR-153-3p on high glucose-stimulated human glomerular mesangial cells. MATERIALS AND METHODS: The quantitative real-time polymerase chain reaction (qPCR) assay was employed to check miR-153-3p and PAQR3 expression levels in diabetic nephropathy patients. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay was applied to investigate the effects of miR-153-3p transfection or PAQR3 administration on mesangial cell (MC) activity. ELISA assays were used to check the expression levels of extracellular matrix (ECM) related proteins. The bioinformatics method and dual-luciferase reporter assay were employed together to anticipate and check the targeting relationship between miR-153-3p and PAQR3. Western blot assays were applied to check the PAQR3, PI3K and AKT expression after miR-153-3p transfection or PAQR3 administration. RESULTS: The expression level of miR-153-3p was lower in diabetic nephropathy patients, while the expression of PAQR3 was concomitantly higher. Upregulation of miR-153-3p can reduce MC proliferation and ECM accumulation. Further research indicated that miR-153-3p directly regulated PAQR3 expression via coupling with the 3'-UTR of PAQR3. Finally, the fact that miR-153-3p regulates the PI3K/AKT pathway by PAQR3 was confirmed. CONCLUSION: MiR-153-3p regulates the PI3K/AKT pathway through PAQR3, thereby playing a role in regulating cell proliferation and ECM accumulation in high glucose-stimulated MCs.

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Long noncoding RNAs (lncRNAs) have been regarded as modulators of neurodegenerative diseases. Here, we addressed the role of lncRNA miR-17-92a-1 cluster host gene (MIR17HG) in Parkinson's disease (PD). C57BL/6 mice and SH-SY5Y cells were intervened with 6-hydroxydopamine (6-OHDA) to set up PD models in vivo and in vitro. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was implemented to compare the expression of MIR17HG and miR-153-3p. Cell viability and apoptosis were estimated by 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and Western blot (WB). The expression of alpha-synuclein (α-syn, SNCA) in BV2 was validated by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) generation and lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activity were evaluated using commercially available kits. Bioinformatics analysis, the dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and qRT-PCR were conducted to demonstrate the interactions between miR-153-3p, MIR17HG, and alpha-synuclein (SNCA). MIR17HG was up-regulated while miR-153-3p was down-regulated in PD patients, mouse models and cells. Inhibiting MIR17HG attenuated neuronal apoptosis, microglial activation and SNCA expression in PD mice. Conditioned medium from 6-OHDA-treated SH-SY5Y cells intensified microglial inflammation, while inhibition of MIR17HG or overexpression of miR-153-3p restrained the inflammatory responses. MIR17HG's function was enforced by sponging miR-153-3p and releasing the attenuation of the putative targets of miR-153-3p and SNCA. Overall, MIR17HG, by targeting miR-153-3p and up-regulating SNCA, stimulates neuronal apoptosis and microglial inflammation in PD.

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Cervical cancer (CC) is a common malignancy in gynecology. Emerging evidence has demonstrated that circular RNAs (circRNAs) act as vital mediators in CC. However, the roles of circRNA ring finger protein 121 (circRNF121) in CC are largely unknown. Herein, we focused on the exact function and underlying mechanism of circRNF121 in CC development. Our results showed that circRNF121 was highly expressed in CC tissues and cells. Knockdown of circRNF121 suppressed cell growth, metastasis, epithelial-mesenchymal transition (EMT), autophagy, and wnt/ß-catenin pathway in CC cells in vitro and blocked tumor formation in vivo. For mechanism investigation, circRNF121 could affect activating transcription factor 2 (ATF2) expression by decoying miR-153-3p, thereby accelerating CC cell development. In conclusion, circRNF121 exerted the tumor-suppressive role in CC progression by altering miR-153-3p/ATF2 axis. These results suggested that circRNF121 might be a possible circ-targeted therapy for patients with CC.

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Colorectal cancer (CRC) is regarded as one of the commonest cancer types around the world. Due to the poor understanding on the causes of CRC formation and progression, this study sets out to investigate the physiological mechanisms by which Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (ARCR) regulates CRC growth and metastasis, and the role in which M2 macrophage polarization plays in this process. An orthotopic-transplant model of CRC was established to evaluate the influence of ARCR on the polarization of M2 macrophage and the growth and metastasis of tumors. Next, the binding affinity among Sp1, ZFAS1, miR-153-5p, and CCR5 was identified using multiple assays. Finally, after co-culture of bone marrow-derived macrophages (BMDM) with CRC cell line CT26.WT, the cell proliferative, invasive, and migrated abilities were assessed in gain- or loss-of-function experiments. ARCR inhibited the infiltration of M2 macrophages into tumor microenvironment to suppress the CRC growth and metastasis in vivo. Additionally, ARCR inhibited the transcription of ZFAS1 by reducing Sp1 expression to repress M2 macrophage polarization. Moreover, ZFAS1 competitively binds to miR-153-3p to upregulate the CCR5 expression. Finally, ARCR suppressed the polarization of M2 macrophages to inhibit the tumor growth and tumor metastasis in CRC by mediating the Sp1/ZFAS1/miR-153-3p/CCR5 regulatory axis. Collectively, ARCR appears to suppress the CRC cell growth and metastasis by suppressing M2 macrophage polarization via Sp1/ZFAS1/miR-153-3p/CCR5 regulatory axis. 1. ARCR suppress the CRC cell growth and metastasis 2. ZFAS1 promotes CCR5 expression by competitively binding to miR-153-3p. 3. Sp1 promotes M2 macrophage polarization by activating ZFAS1 via miR-153-3p/CCR5. 4. The study unveiled a protective target against CRC.

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Gastric cancer (GC) is the second leading cause of cancer-related mortality worldwide. MicroRNAs (miRNAs) have been extensively reported to play a role in GC development; however, it remains unknown whether miR-153-3p participates in the nosogenesis of GC. GC tissues along with the adjacent nontumor tissues were obtained from 50 patients with GC. Moreover, we incubated human GC cell lines (SGC7901, AGS, MGC803, and BGC823) and a gastric epithelial cell line (GES-1) and then transfected BGC823 cells with miR-153-3p and DNA/SphK2 vector to determine the action of miR-153-3p and SphK2 on GC. RT-qPCR was performed to determine the levels of miR-153-3p and sphingosine kinase 2 (SphK2). The viability of BGC823 cells was measured by the CCK-8 assay, while wound healing assays and transwell assays were used to measure the migration and invasion ability of BGC823 cells. Western blotting analysis and immunohistochemistry (IHC) were conducted to evaluate the level of SphK2. The binding ability of miR-153-3p and SphK2 was determined by dual-luciferase reporter assays. The expression level of miR-153-3p was reduced in GC tissues and cells, while the SphK2 was enhanced. An increase in miR-153-3p level led to a decline in the growth and metastasis of GC cells and increased their apoptosis. Moreover, a decrease in miR-153-3p level elevated GC cells growth and metastasis, and attenuated their apoptosis. SphK2 was also corroborated as a downstream gene of miR-153-3p. Here, SphK2 expression was elevated in GC tissues and cells, indicating SphK2 might be involved in the development of GC. Rescue assays showed that miR-153-3p could reverse the effect of SphK2 on the cell growth, metastasis, and the apoptosis of GC cells. In conclusion, this study showed that miR-153-3p suppressed the growth and metastasis in GC cells by regulating SphK2, which might facilitate the search for novel biomarkers to treat GC.

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BACKGROUND: Breast cancer is an aggressive tumor, which poses a heavy burden to human health. Circular RNAs have been involved in the pathogenesis of breast cancer. This study aims to investigate whether circ_0008673 mediates breast cancer malignant progression by microRNA-153-3p (miR-153-3p)/cofilin 2 (CFL2) pathway. METHODS: The RNA levels of circ_0008673, miR-153-3p and CFL2 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of CFL2, E-cadherin and N-cadherin was determined by western blot analysis. Cell proliferation was demonstrated through cell counting kit-8 and cell colony-formation assays. Cell apoptosis was detected by flow cytometry analysis. Cell migratory and invasive capacities were determined by transwell assay. The associated relationship between miR-153-3p and circ_0008673 or CFL2 was predicted by online databases, and testified by dual-luciferase reporter and RNA immunoprecipitation assays. In vivo assay was employed to demonstrate the effects of circ_0008673 silencing on tumor formation in vivo. RESULTS: Circ_0008673 and CFL2 expressions were upregulated, while miR-153-3p expression was downregulated in breast cancer tissues and cells compared with adjacent normal breast tissues and cells, respectively. Circ_0008673 overexpression promoted cell proliferation, migration and invasion, and repressed cell apoptosis, while circ_0008673 silencing had opposite effects. Additionally, circ_0008673 served as a sponge of miR-153-3p. And circ_0008673 was proved to regulate breast cancer cell malignancy by sponging miR-153-3p. MiR-153-3p was found to modulate breast cancer cell carcinogenesis via targeting CFL2. Furthermore, circ_0008673 silencing repressed tumor growth in vivo. CONCLUSION: Circ_0008673 promoted breast cancer progression by upregulating CFL2 expression through sponging miR-153-3p. This study provides a theoretical basis for researching circRNA-directed treatment of breast cancer.

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@#Objective　To investigate the mechanism of CirCDC14A silencing to protect astrocytes from oxygen-glucose deprivation/glyco-reoxygenation (OGD/R)-induced injury by regulating the miR-153-3p/JAK1 axis.Methods　Cerebral cortical astrocytes of neonatal rats were cultured in vitro,and the cell viability was detected by CCK-8 method;annexin V-FITC/PI staining was used to detect cell apoptosis.Western blot method was used to detect the protein expression levels of p53,Bax and Bcl-2 in each group,and the relationship between CirCDC14A and miR-153- 3p,miR-153-3p and JAK1 was analyzed by dual-luciferase reporter gene assay.Results　The cell viability increased with time; the cell viability of pcDNA3.0 CirCDC14A+si JAK1 group at 48 h and 72 h was lower than that of si-NC group,OGD/R group and OGD/R+Si+Con mimcs group (P<0.05);compared with si-NC group,the apoptosis of OGD/R group,OGD/R+Si+Con mimcs group,pcDNA3.0-CirCDC14A+si JAK1+miR-153-3p mimcs group increased significantly,and pcDNA3.0-CirCDC14A+si JAK1+miR-153-3p mimcs group had higher apoptosis than OGD/R+Si+Con mimcs group (P<0.05);Western blot results showed that:pcDNA3.0-CirCDC14A+si JAK1+miR,the protein expression levels of p53,Bax and Bcl-2 in the miR-153-3p mimcs group were lower than those in the OGD/R group,OGD/R+Si+Con mimcs group and si-NC group (P<0.05).Reduced the luciferase activity of CirCDC14A WT and JAK1-WT (P<0.05); the level of miR-153-3p in the pcDNA3.0-CirCDC14A+si JAK1+miR-153-3p mimcs group was lower than that in the other three groups (P<0.05). The JAK1 protein level was higher than the other three groups (P<0.05).Conclusion　CirCDC14A gene silencing may inhibit OGD/R-induced apoptosis of rat astrocytes by regulating the miR-153-3p/JAK1 axis,resulting in decreased cell viability and protein expression levels of p53,Bax and Bcl-2.