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OBJECTIVE: This study was to investigate the clinical significance of miR-551b-5p and SETD2 in thyroid cancers (TC) and their effects on the biological function of TC cells. METHODS: The expression level of miR-551b-5p and SETD2 in tumor/nontumor tissues and TC cell lines was measured by quantitative real-time polymerase chain reaction (RT-qPCR). Subsequently, the relationship between miR-551b-5p or SETD2 expression and the clinicopathological feature was detected by Chi-square analysis. Kaplan-Meier and multivariate Cox regression analyses were used to assess their prognostic values. Finally, the regulatory effects of miR-551b-5p and SETD2 on the proliferation, migration and invasion ability of TC cells were detected by CCK-8 and Transwell assays. RESULTS: Compared with non-tumor groups, the expression of miR-551b-5p was significantly increased in patients' tissues and TC cell lines, while SETD2 mRNA expression was decreased. Patients with up-regulated miR-551b-5p or downregulated SETD2 mRNA in TC showed more positive lymph node metastasis and advanced TNM stage. High miR-551b-5p expression level and low SETD2 mRNA level were related to poor survival rate. miR-551b-5p and SETD2 might be potential prognostic biomarkers for TC. miR-551b-5p knockdown can inhibit cell proliferation, migration and invasion by targeting SETD2. CONCLUSION: miR-551b-5p and SETD2 may be valuable prognostic biomarkers and new therapeutic targets for TC.

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Understanding human skin photoaging requires in-depth knowledge of the molecular and functional mechanisms. Human dermal fibroblasts (HDFs) gradually lose their ability to produce collagen and renew intercellular matrix with aging. Therefore, our study aims to reveal the mechanistic actions of a novel ceRNA network in the skin photoaging by regulating HDF activities. Photoaging-related genes were obtained in silico, followed by GO and KEGG enrichment analyses. Differentially expressed lncRNAs and miRNAs were screened from the GEO database to construct the ceRNA co-expression network. In skin photoaging samples, PVT1 and AQP3 were poorly expressed, while miR-551b-3p was highly expressed. The relationships among the lncRNA, miRNA and mRNA were explored through the ENCORI database and dual luciferase reporter assay. Mechanistically, PVT1 could sequester miR-551b-3p to upregulate the expression of AQP3, which further inactivated the ERK/p38 MAPK signaling pathway. HDFs were selected to construct an in vitro cell skin photoaging model, where the senescence, cell cycle distribution and viability of young and senescent HDFs were detected by SA-ß-gal staining, flow cytometry and CCK-8 assay. In vitro cell experiments confirmed that overexpression of PVT1 or AQP3 enhanced viability of young and senescent HDFs and inhibited HDF senescence, while miR-551b-3p upregulation counteracted the effect of PVT1. In conclusion, PVT1-driven suppression of miR-551b-3p induces AQP3 expression to inactivate the ERK/p38 MAPK signaling pathway, thereby inhibiting HDF senescence and ultimately delaying the skin photoaging.

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As a novel form of repetitive transcranial stimulation, intermittent theta burst stimulation (iTBS) has potentials to be widely used in patients with stroke. Yet little is known about the idiographic actions of iTBS with different stimulation parameters on rehabilitative aspects of stroke patients, nor is the molecular mechanism underlying. In the present study, effects of iTBS with different stimulation parameters were evaluate to identify the optimal protocol of iTBS against damage induced by ischemia/reperfusion (I/R). Herein we found the short-term iTBS application seemed to have no significant effects on outcomes of rats during acute phase after I/R, including the neurological deficits, cerebral infarction and edema. However, behavioral functional tests demonstrated that long-term iTBS treatment provided effective therapy during subacute stage after two weeks post-stroke onset, which possibly by increasing proliferation and migration of adult neural stem cells. To explore the possible mechanisms of, microRNAs (miRs) expressional profiles were analyzed by microarray technology. Further bioinformatic analysis of binding sites revealed miR-551b-5p directly targeted the brain-derived neurotrophic factor (BDNF), which was confirmed by luciferase reporter and qRT-PCR. Moreover, the level phosphorylated-TrkB, the downstream of BDNF, was elevated accompanied by above-mentioned changes of long-term iTBS. Taken together, experimental data reveals a direct link between miR-551b-5p and BDNF-mediated signaling cascade in early convalescence of stroke. Our findings provide new insights into the molecular mechanisms underlying curative effects of iTBS on stroke, thus aiding in the prognosis and personalized therapies.

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BACKGROUND: Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) plays a crucial role in non-small cell lung cancer (NSCLC). Nonetheless, regulatory effects of PVT1 on functions of NSCLC cells remain blurry. METHODS: Relative expression levels of PVT1, miR-551b and FGFR1 mRNA in tumor tissues and cells were examined employing quantitative real-time polymerase chain reaction (qRT-PCR); CCK-8 and BrdU assays were utilized for measuring cell viability and proliferation of H1299 and A549 cells; cell migration and invasion were detected deploying Transwell assay; dual-luciferase assay was used for the validation of binding sequence between PVT1 and miR-551b. FGFR1 expression in protein level was quantified employing Western blot. RESULTS: PVT1 was highly expressed in NSCLC tissues and cell lines, whereas miR-551b expression was down-regulated. Overexpression of PVT1 potentiated viability, proliferation, migration and invasion of NSCLC cells while miR-551b inhibited the biological behaviors mentioned above. MiR-551b was predicted and then confirmed as a direct downstream target of PVT1. Meanwhile, a negative correlation was observed between PVT1 expression and miR-551b expression in NSCLC tissues. Besides, PVT1 could increase FGFR1 expression by repressing miR-551b expression. CONCLUSION: PVT1 promotes the proliferation, migration and invasion of NSCLC cells by indirectly mediating FGFR1 via targeting miR-551b.

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INTRODUCTION: Long intergenic non-protein coding RNA 665 (LINC00665) has been revealed to contribute cancer progression in many cancer types including liver and gastric cancer. However, the roles of LINC00665 in breast cancer (BC) remain to be explored. METHODS: We explored LINC00665 expression in BC tissues and normal tissues at GEPIA. Then, its expression in BC cells (HCC-1937, MDA-MB-231, and MCF-7) and normal cells (MCF10A) was analyzed with qRT-PCR. In addition, the mechanisms of LINC00665 in BC were explored using bioinformatic analyses, luciferase activity reporter assay, RNA pull-down assay, and rescue experiments. RESULTS: We showed LINC00665 expression was significantly increased in both BC tissues and cells. The knockdown of LINC00625 significantly inhibits BC cell growth and promotes cell apoptosis in vitro, while the overexpression of LINC00625 has the opposite effects on BC progression. LINC00665 could affect BC progression via regulating miR-551b-5p. DISCUSSION: Taken together, our study showed that the LINC00665/miR-551b-5p axis was involved in the progression of BC.

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Malignant pleural mesothelioma (MPM) is a malignant tumor which is a challenge for diagnosis and is associated with a poor patient prognosis. Thus, early diagnostic interventions will improve the quality of life and life expectancy of these patients. Recently, cellular microRNAs (miRNAs) have been found to be involved in maintaining homeostasis, and abnormal miRNA expression has often been observed in various diseases including cancer. Extracellular vesicles (EVs) released by many cells contain proteins and nucleic acids. miRNAs are secreted from all cells via EVs and circulate throughout the body. In this study, culture media were passed sequentially through membrane filters 220­50 nm in size, and EVs with diameters of 50 to 220 nm (EVcap50/220) were collected. miRNAs (EV50­miRNAs) in EVcap50/220 were purified, and microarray analysis was performed. EV50­miRNA expression profiles were compared between MPM cells and a normal pleural mesothelial cell line, and six EV50­miRNAs were selected for further investigation. Of these, hsa­miR­193a­5p and hsa­miR­551b­5p demonstrated higher expression in MPM­derived EVcap50/220. These miRNAs reduced the expression of several genes involved in cell­cell interactions and cell­matrix interactions in normal pleural mesothelial cells. Our data suggest that hsa­miR­193a­5p and hsa­miR­551b­5p in EVcap50/220 could be diagnostic markers for MPM.

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Accumulating reports have demonstrated that long non-coding RNAs (lncRNAs) play critical roles in the occurrence and metastasis of cholangiocarcinoma (CCA). LncRNA myocardial infarction associated transcript (MIAT) has been widely reported in hepatocellular carcinoma, pancreatic cancer and colorectal cancer, but the relationship between MIAT and CCA progression has not yet been investigated. In the present study, we found that the expression of MIAT in CCA tissues was prominently higher than that in normal bile duct tissues. Moreover, TCGA-CHOL data in the GEPIA platform further revealed the upregulated expression of MIAT in CCA tissues. Additionally, quantitative real-time PCR results showed that MIAT expression was increased in CCA cell lines compared to the human intrahepatic biliary epithelial cell line. Functionally, MIAT knockdown significantly inhibited cell proliferation and induced G0/G1 phase arrest as well as apoptosis in HuCCT-1 and QBC939 cells. Conversely, ectopic expression of MIAT obviously facilitated the proliferation, cell cycle progression and apoptosis resistance of RBE cells. Mechanistically, MIAT directly interacted with miR-551b-3p and inversely modulated miR-551-3p level in CCA cells. Furthermore, MIAT knockdown reduced the expression of cyclin D1 (CCND1), which was rescued by miR-551b-3p silencing in HuCCT-1 cells. Importantly, CCND1 restoration partially reversed MIAT knockdown-induced proliferation inhibition, G0/G1 phase arrest and apoptosis in HuCCT-1 cells. In conclusion, MIAT was frequently overexpressed in CCA. MIAT contributed to the growth of CCA cells by targeting miR-551b-3p/CCND1 axis.

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Genomic amplification of 3q26.2 locus leads to the increased expression of microRNA 551b-3p (miR551b-3p) in triple-negative breast cancer (TNBC). Our results demonstrate that miR551b-3p translocates to the nucleus with the aid of importin-8 (IPO8) and activates STAT3 transcription. As a consequence, miR551b upregulates the expression of oncostatin M receptor (OSMR) and interleukin-31 receptor-α (IL-31RA) as well as their ligands OSM and IL-31 through STAT3 transcription. We defined this set of genes induced by miR551b-3p as the "oncostatin signaling module," which provides oncogenic addictions in cancer cells. Notably, OSM is highly expressed in TNBC, and the elevated expression of OSM associates with poor outcome in estrogen-receptor-negative breast cancer patients. Conversely, targeting miR551b with anti-miR551b-3p reduced the expression of the OSM signaling module and reduced tumor growth, as well as migration and invasion of breast cancer cells.

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Background: We generated a rat model of diabetic cardiomyopathy (DCM) and reported significant upregulation of the long non-coding RNA DCRF. This study was designed to determine the molecular mechanisms of DCRF in the development of DCM. Methods: Real-time PCR and RNA fluorescent in situ hybridization were conducted to detect the expression pattern of DCRF in cardiomyocytes. Histological and echocardiographic analyses were used to assess the effect of DCRF knockdown on cardiac structure and function in diabetic rats. mRFP-GFP-LC3 fluorescence microscopy, transmission electron microscopy, and Western blotting were carried out to determine cardiomyocyte autophagy. RNA immunoprecipitation and luciferase reporter assays were performed to elucidate the regulatory role of DCRF/miR-551b-5p/PCDH17 pathway in cardiomyocyte autophagy. Results: Our findings showed that DCRF knockdown reduced cardiomyocyte autophagy, attenuated myocardial fibrosis, and improved cardiac function in diabetic rats. High glucose increased DCRF expression and induced autophagy in cardiomyocytes. RNA immunoprecipitation and luciferase reporter assays indicated that DCRF was targeted by miR-551b-5p in an AGO2-dependent manner and PCDH17 was the direct target of miR-551b-5p. Forced expression of DCRF was found to attenuate the inhibitory effect of miR-551b-5p on PCDH17. Furthermore, DCRF knockdown decreased PCDH17 expression and suppressed autophagy in cardiomyocytes treated with high glucose. Conclusion: Our study suggests that DCRF can act as a competing endogenous RNA to increase PCDH17 expression by sponging miR-551b-5p, thus contributing to increased cardiomyocyte autophagy in DCM.

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Our current understanding of the role of microRNA 551b (miR551b) in the progression of colorectal cancer (CRC) remains limited. Here, studies using both ectopic expression of miR551b and miR551b mimics revealed that miR551b exerts a tumor suppressive effect in CRC cells. Specifically, miR551b was significantly downregulated in both patient-derived CRC tissues and CRC cell lines compared to normal tissues and non-cancer cell lines. Also, miR551b significantly inhibited the motility of CRC cells in vitro, including migration, invasion, and wound healing rates, but did not affect cell proliferation. Mechanistically, miR551b targets and inhibits the expression of ZEB1 (Zinc finger E-box-binding homeobox 1), resulting in the dysregulation of EMT (epithelial-mesenchymal transition) signatures. More importantly, miR551b overexpression was found to reduce the tumor size in a xenograft model of CRC cells in vivo. Furthermore, bioinformatic analyses showed that miR551b expression levels were markedly downregulated in the advanced-stage CRC tissues compared to normal tissues, and ZEB1 was associated with the disease progression in CRC patients. Our findings indicated that miR551b could serve as a potential diagnostic biomarker and could be utilized to improve the therapeutic outcomes of CRC patients.

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Circulating microRNAs have the potential to be noninvasive biomarkers for assessing disease progression. MicroRNA-551b-5p (miR-551b-5p) was previously reported to be differentially expressed in pancreatic patients. The serum miR-551b-5p level was measured in patients with mild acute pancreatitis (MAP), severe acute pancreatitis (SAP), and healthy controls using quantitative real-time polymerase chain reaction (RT-PCR) analysis to evaluate its impact on inflammatory response. Acute Physiology and Chronic Health Evaluation II (APACHE II), Multiple Organ Dysfunction Score (MODS), Sequential Organ Assessment Score (SOFA), and Ranson's scores were recorded. Inflammatory cytokines, IL-6, IL-17, IL-1ß, and Tumor Necrosis Factor-α (TNF-α), were detected in serum samples obtained from MAP and SAP patients on admission day 1, day 3, and day 5 using Enzyme Linked Immunosorbent Assay (ELISA). Inflammatory cytokines were analyzed in peripheral blood mononuclear cells (PBMCs), which were transfected with miR-551b-5p-negative controls and inhibitors. The serum miR-551b-5p level was significantly higher in MAP and SAP patients compared to controls (P < 0.001). An elevated miR-551b-5p level is positively associated with APACHE II, MODS, SOFA, and Ranson's scores (P < 0.001). Serum cytokines levels were significantly elevated in MAP and SAP patients compared to controls (P < 0.05). In addition, the level of these inflammatory cytokines was increased in PBMCs of SAP patients in comparison with those of healthy controls (P < 0.05), and this rise was significantly reduced with the addition of an miR-551b-5p inhibitor. In conclusion, serum miR-551b-5p is elevated in patients with MAP and SAP and is involved in the regulation of inflammatory response. It may be a useful biomarker for assessing the severity of SAP.

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Decreased expression of miR-551b-3p has been identified in gastric cancer tissues but its biological role and underlying mechanism in this malignancy is poorly understood. In this study, we show that the expression of miR-551b-3p negatively correlates with the depth of tumour invasion and lymphatic metastasis, but it positively correlates with tumour differentiation and the patient survival. MiR-551b-3p negatively affects the proliferation, mobility and invasiveness of gastric cancer cells. LncRNA SMARCC2 inhibits the expression of miR-551b-3p through binding to its mRNA response elements in gastric cancer cells. Overexpression of LncRNA SMARCC2 enhances the proliferation and migration of gastric cancer cells, while inhibition of LncRNA SMARCC2 does the opposite. TMPRSS4 is a direct target gene of miR-551b-3p. We conclude that miR-551b-3p functions as a tumour suppressor gene in gastric cancer, and its function is regulated by LncRNA SMARCC2/miR-551b-3p/TMPRSS4 axis.

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miR-551b has been reported to be involved in tumorigenesis, cell invasion, and metastasis in gastric cancer but the mechanism remains unclear. In this study, in an attempt to address this question, we examined expression of miR-551b in gastric tumors and adjacent normal tissue. We transfected SGC-7901 gastric cancer cells with miRNA non-sense sequences (NC group), miR-551b mimics (miR-551b mimic group), and miR-551b inhibitors (miR-551b inhibitor group) to investigate the role of miR-551b in autophagic apoptosis. In gastric tissue, our real-time PCR results revealed that expression of miR-551b was significantly downregulated and the relative expression of miR-551b (1.75 ± 0.13) was significantly lower than in normal tissue (2.47 ± 0.38) (P<0.05). In transfected SGC-7901 cells, compared with the NC and miR-551b inhibitor group, miR-551b expression level and apoptosis rate in miR-551b mimics group was significantly increased whereas proliferation and invasion rates were significantly decreased (P<0.05). Hoechst 33342 fluorescence staining showed that a large number of autophagosomes were detected in miR-551b mimic group, fewer in the NC group, and only a small number in miR-551b inhibitor group. Western blotting showed that expression levels of NF-κB, LC3 II, and Beclin 1 in miR-551b mimics group were significantly higher than in the NC group and miR-551b inhibitor group (P<0.05). Our findings suggest that miR-551b could inhibit proliferation, apoptosis, and invasion of gastric cancer cells and the action mechanism may be related to induction of gastric cancer cells autophagic apoptosis.

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Epithelial-mesenchymal transition (EMT) is an important biological process that is characteristic of malignant tumor cells with metastatic potential. We investigated the role of miR-551b in EMT and metastasis in gastric cancer (GC). We found that low miR-551b levels were associated with EMT, metastasis and a poor prognosis in GC patients. Further, two GC cell lines, MNK45 and SGC7901, exhibited lower miR-551b levels than the GES normal stomach cell line. Exposing MNK45 and SGC7901 cells to TGF-ß1 resulted in cell morphology changes characteristic of EMT, which was confirmed by Western blot analysis demonstrating low E-Cadherin and high N-Cadherin and Vimentin levels. Treatment with miR-551b mimics inhibited these EMT changes as well as Transwell migration and invasiveness. We identified ERBB4 as a potential target of miR-551b based on patient data from the TCGA. ERBB4 was upregulated in GC specimens, and its high expression correlated with a poor prognosis of GC patients. Dual luciferase assays revealed that miR-551b directly inhibited ERBB4 by binding to its 3'UTR. Moreover, treatment with miR-551b mimics or the ERBB4 inhibitor AST-1306 inhibited EMT in the GC cell lines. Finally, nude mice xenografted with GC cancer cell lines expressing miR-551b mimics exhibited smaller tumors and longer survival than mice engrafted with control GC cancer cells. These data indicate that miR-551b inhibits EMT and metastasis in GC by inhibiting ERBB4. miR-551b and ERBB4 are thus potential therapeutic targets for the treatment of GC.

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Ovarian cancer (OVCa) stem cells are associated with tumor growth, metastasis, and recurrence, which are driving forces behind a majority of the OVCa-related mortality. This subpopulation of cancer cells are characterized by uncontrolled proliferation, high invasiveness, and resistance against the current platinum-based therapy. Thus, targeting OVCa cancer stem cells has been focused in recent therapeutic development. Isolation and purification of cancer stem cells are, however, challenging for the lack of sensitive and specific markers. In this study, we demonstrated that miR-551b was upregulated in OVCa stem cells, by using a quantitative PCR array, correlating with the pathological grades of this malignancy. In vitro experiments indicated that miR-551b promoted the proliferation, invasion, and chemoresistance of OVCa cells and cancer stem cells. Further analysis suggested that miR-551b functioned through the suppression of Foxo3 and TRIM31, two important tumor suppressors. In support of this, our in vivo experiments using mouse xenograft models showed that inhibiting miR-551b significantly increased the susceptibility of OVCa cells to cisplatin and prolonged the survival of the host mice. In conclusion, our study suggested miR-551b as a potential biomarker for OVCa stem cells and explored its functional mechanism, providing a potential therapeutic target for future drug development.

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