CirRNA circFAM126A Exerts Oncogenic Functions in NSCLC to Upregulate IRS2.

Non-small cell lung cancer (NSCLC) is a common histological subtype of lung cancer, which occupies 80-85% of the proportion in all lung cancer cases. Therefore, this study was designed to clarify the role and underlying molecular mechanisms of circFAM126A in NSCLC. The real-time quantitative polymerase chain reaction (RT-qPCR) assay was conducted to assess circFAM126A, FAM126A, miR-613, and IRS2 expression in NSCLC tissues and cells. The proliferation ability of cells was measured by MTT, EdU, and colony-forming assays. The flow cytometry assay was performed to evaluate cell cycle distribution and apoptosis of NSCLC cells. The migration and invasion were determined by wound healing and transwell matrigel assays, respectively. The interaction relationship between miR-613 and circFAM126A or IRS2 was analyzed by dual-luciferase reporter and RNA pull-down assays. Tumorigenesis in nude mice was conducted to clarify the functional roles of circFAM126A inhibition in vivo. CircFAM126A was obviously overexpressed in NSCLC tissues and cells when compared with controls. The loss-of-functional experiments suggested that knockdown of circFAM126A suppressed proliferation, migration and invasion, as well as caused apoptosis and cell cycle arrest in NSCLC cells, which was abolished by silencing of miR-613. In addition, IRS2 was a target gene of miR-613. Overexpression of miR-613 exerted carcinoma inhibitor role in NSCLC by inhibition of IRS2 expression. Consistently, the silencing of circFAM126A also functioned anti-tumorigenic roles in nude mice in vivo. Mechanistically, circFAM126A could function as a miRNA sponge for miR-613 to regulate the expression of IRS2, thereby regulating proliferation, migration, invasion, apoptosis, and cell cycle arrest in NSCLC cells.

MiR-613 inhibits the proliferation, migration, and invasion of papillary thyroid carcinoma cells by directly targeting TAGLN2.

BACKGROUND: Papillary thyroid carcinoma (PTC), with a rapidly increasing incidence, is the most prevalent malignant cancer of the thyroid. However, its pathogenesis is unclear and its specific clinical indicators have not yet been identified. There is increasing evidence that microRNAs (miRNAs) play important roles in tumor occurrence and progression. Specifically, miR-613 participates in the regulation of tumor development in various cancers; however, its effects and mechanisms of action in PTC are still unclear. Therefore, in this study, we investigated the expression and function of miR-613 in PTC. METHODS: qRT-PCR was used to determine miR-613 expression in 107 pairs of PTC and adjacent-normal tissues as well as in PTC cell lines and to detect TAGLN2 mRNA expression in PTC tissues and adjacent normal tissues. Western blot analysis was performed to identify TAGLN2 and epithelial-mesenchymal transition (EMT) biomarkers. The effects of miR-613 on PTC progression were evaluated by performing MTS, wound-healing, and Transwell assays in vitro. Luciferase reporter assays were also performed to validate the target of miR-613. RESULTS: In PTC, miR-613 was significantly downregulated and its low expression level was associated with cervical lymph node metastasis. However, its overexpression significantly suppressed PTC cell proliferation, migration, and invasion and inhibited EMT. TAGLN2 was identified as a target of miR-613, which also significantly inhibited the expression of TAGLN2. Further, the restoration of TAGLN2 expression attenuated the inhibitory effects of miR-613 on PTC cell proliferation and metastasis. CONCLUSION: Our findings demonstrated that miR-613 can suppress the progression of PTC cells by targeting TAGLN2, indicating that miR-613 plays the role of a tumor suppressor in PTC. Overall, these results suggest that the upregulation of miR-613 is a promising therapeutic strategy for PTC.

Long noncoding RNA CCAT1 inhibits miR-613 to promote nonalcoholic fatty liver disease via increasing LXRα transcription.

Nonalcoholic fatty liver disease (NAFLD) is regarded as a threat to public health; however, the pathologic mechanism of NAFLD is not fully understood. We attempted to identify abnormally expressed long noncoding RNA (lncRNAs) and messenger RNA that may affect the occurrence and development of NAFLD in this study. The expression of differentially expressed lncRNAs in NAFLD was determined in oleic acid (OA)-treated L02 cells, and the functions of CCAT1 in lipid droplet formation were evaluated in vitro. Differentially expressed genes (DEGs) were analyzed by microarray analysis, and DEGs related to CCTA1 were selected and verified by weighted correlation network analysis. The dynamic effects of LXRα and CCTA1 on lipid droplet formation and predicted binding was examined. The binding between miR-631 and CCAT1 and LXRα was verified. The dynamic effects of miR-613 inhibition and CCTA1 silencing on lipid droplet formation were examined. The expression and correlations of miR-631, CCAT1, and LXRα were determined in tissue samples. As the results show, CCAT1 was induced by OA and upregulated in NAFLD clinical samples. CCAT1 silencing significantly suppressed lipid droplet accumulation in vitro. LXRα was positively correlated with CCAT1. By inhibiting miR-613, CCAT1 increased the transcription of LXRα and promoted LXRα expression. The expression of LXRα was significantly increased in NAFLD tissues and was positively correlated with CCAT1. In conclusion, CCAT1 increases LXRα transcription by serving as a competing endogenous RNA for miR-613 in an LXRE-dependent manner, thereby promoting lipid droplet formation and NAFLD. CCAT1 and LXRα might be potent targets for NAFLD treatment.

LncRNA HOTAIR modulates the expression of OATP1B1 in HepG2 cells by sponging miR-206/miR-613.

OATP1B1 is an important drug transporter with a complex regulatory mechanism. In this study, we wanted to investigate how LncRNA HOTAIR regulates the expression of OATP1B1 through its action on miR-206/miR-613 in HepG2 cells. The expression level of LncRNA HOTAIR, miR-206/miR-613, and OATP1B1 mRNA was detected by RT-qPCR, and the OATP1B1 protein level was detected by Western blot. The competitive endogenous RNA mechanism was validated by bioinformatics analysis and a dual-luciferase reporter gene assay. Our results showed that over- or under-expression of LncRNA HOTAIR correspondingly significantly increased or decreased the protein level of OATP1B1 in HepG2 cells, while no significant change in OATP1B1 mRNA level was observed. In addition, the stimulatory or inhibitory effect of LncRNA HOTAIR on OATP1B1 protein expression was correspondingly reversed by miR-206/miR-613 mimic or miR-206/miR-613 inhibitor. Finally, the reporter gene assay revealed that LncRNA HOTAIR can sponge miR-206/miR-613, which breaks the binding site of miR-206/miR-613 and OATP1B1 mRNA 3'-UTR, eliminating the stimulatory effect of LncRNA HOTAIR on OATP1B1 protein. Thus, we conclude that LncRNA HOTAIR can affect the expression of OATP1B1 in HepG2 cells by sponging miR-206/miR-613, which, in turn, prevents the binding of miR-206/miR-613 and OATP1B1 mRNA 3'-UTR.

LncRNA SNHG14 potentiates pancreatic cancer progression via modulation of annexin A2 expression by acting as a competing endogenous RNA for miR-613.

This study aimed to determine long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) expression in pancreatic cancer and to explore the potential molecular actions of SNHG14 in mediating pancreatic cancer progression. Gene expression was detected by quantitative real-time PCR. Cell proliferation, growth and invasion were detected by respective CCK-8, colony formation, and transwell invasion assays. Protein levels were measured by Western blotting. Cell apoptosis and caspase-3 activity were detected by flow cytometry and caspase-3 activity assay. The link between miR-613 and its targets was evaluated by luciferase reporter assay. In vivo tumour growth was evaluated using a xenograft model of nude mice. SNHG14 expression was up-regulated in cancerous tissues from pancreatic cancer patients. High expression of SNHG14 was associated with poor tumour differentiation, advanced TNM stage and nodal metastasis. SNHG14 overexpression enhanced cell proliferative, growth and invasive abilities, and suppressed apoptotic rates and caspase-3 activity in pancreatic cancer cells, while SNHG14 knockdown exerted opposite effects. Mechanistic studies revealed that miR-613 was targeted by SNHG14, and Annexin A2 (ANXA2) was targeted and inversely regulated by miR-613 in pancreatic cancer cells. In vivo studies showed that SNHG14 knockdown attenuated tumour growth. MiR-613 was down-regulated and ANXA2 was up-regulated in the pancreatic cancer tissues, and SNHG14 expression levels were inversely correlated with miR-613 expression levels and positively correlated with the ANXA2 mRNA expression levels. Collectively, our results suggest that SNHG14 potentiates pancreatic cancer progression through modulation of annexin A2 expression via acting as a competing endogenous RNA for miR-613.

Long noncoding RNA LINC00460 promotes carcinogenesis via sponging miR-613 in papillary thyroid carcinoma.

Long intergenic noncoding RNA 460 (LINC00460) has been identified as a critical regulator for multiple types of cancers. However, the biological role and underlying mechanism in human papillary thyroid carcinoma (PTC) still remain unclear and need to be uncovered. This study was aimed to ascertain the biological role and molecular mechanism of LINC00460 in PTC progression. Our findings revealed that the level of LINC00460 was significantly upregulated in PTC tissues and cell lines, which was positively correlated with advanced tumor-node-metastasis (TNM) stage and lymph node metastasis. Cellular experiments exhibited that knockdown of LINC00460 decreased proliferative, migratory, and invasive abilities of PTC cells. Mechanism assays noted that knockdown of LINC00460 suppressed cell proliferation, migration, and invasion, and inhibited expression of sphingosine kinase 2 (SphK2, a target of miR-613) in PTC cells, at least in part, by regulating miR-613. These findings suggested that LINC00460 could function as a competing endogenous RNA to regulate SphK2 expression by sponging miR-613 in PTC. Targeting LINC00460 could be a promising therapeutic strategy for patients with PTC.

miR-613 inhibits Warburg effect in gastric cancer by targeting PFKFB2.

miR-613 has been demonstrated to play critical roles in tumorigenesis and progression of a various type of cancers. However, its role and expression significance remain unclear in gastric cancer (GC). We detected the expression of miR-613 in 176 paired GC tissues and adjacent normal tissues, and found that miR-613 was significantly downregulated in GC tissues and its downregulation was correlated with T stage, lymph node invasion and advanced AJCC stages. Moreover, miR-613 expression could be an independent prognostic factor of GC. Biological function analysis indicated that miR-613 inhibited cell proliferation and invasion. Further analysis suggested that miR-613 inhibited Warburg effect of GC cells. Mechanically, we identified that miR-613 could directly bind to the 3'UTR of PFKFB2, thereby suppressing the expression of PFKFB2, which in turn, regulating glycolysis metabolism and cell growth. In conclusion, miR-613 served as a tumor suppressor by targeting PFKFB2, indicating that detecting miR-613 and modulation of miR-613 expression could be potential marker and clinical approach in GC patients.

LncRNA HOTAIR/miR-613/c-met axis modulated epithelial-mesenchymal transition of retinoblastoma cells.

Since lncRNAs could modulate neoplastic development by modulating downstream miRNAs and genes, this study was carried out to figure out the synthetic contribution of HOTAIR, miR-613 and c-met to viability, apoptosis and proliferation of retinoblastoma cells. Totally 276 retinoblastoma tissues and tumour-adjacent tissues were collected, and human retinoblastoma cell lines (ie, Y79, HXO-Rb44, SO-Rb50 and WERI-RB1) were also gathered. Moreover, transfections of pcDNA3.1-HOTAIR, si-HOTAIR, miR-613 mimic, miR-613 inhibitor, pcDNA3.1/c-met were performed to evaluate the influence of HOTAIR, miR-613 and c-met on viability, apoptosis and epithelial-mesenchymal transition (EMT) of retinoblastoma cells. Dual-luciferase reporter gene assay was also arranged to confirm the targeted relationship between HOTAIR and miR-613, as well as between miR-613 and c-met. Consequently, up-regulated HOTAIR and down-regulated miR-613 expressions displayed associations with poor survival status of retinoblastoma patients (P < 0.05). Besides, inhibited HOTAIR and promoted miR-613 elevated E-cadherin expression, yet decreased Snail and Vimentin expressions (P < 0.05). Simultaneously, cell proliferation and cell viability were also less-motivated (P < 0.05). Nonetheless, c-met prohibited the functioning of miR-613, resulting in promoted cell proliferation and viability, along with inhibited cell apoptosis (P < 0.05). Finally, HOTAIR was verified to directly target miR-613, and c-met was the direct target gene of miR-613 (P < 0.05). In conclusion, the role of lncRNA HOTAIR/miR-613/c-met signalling axis in modulating retinoblastoma cells' viability, apoptosis and expressions of EMT-specific proteins might provide evidences for developing appropriate diagnostic and treatment strategies for retinoblastoma.

Long noncoding RNA DANCR aggravates retinoblastoma through miR-34c and miR-613 by targeting MMP-9.

Long non-coding RNAs (lncRNAs) have been identified to play vital roles in cancers, including human retinoblastoma (RB). However, the deepgoing mechanism is still ambiguous. In present study, we investigate the biological role of lncRNA DANCR (differentiation antagonizing non-protein coding RNA) in carcinogenesis of RB. Results revealed that DANCR was up-regulated in RB tissue and cell lines. Moreover, the ectopic overexpression of DANCR indicated poor overall survivals and disease free survival (DFS) for RB patients. In vitro and in vivo experiments, DANCR knockdown suppress the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) correlated protein (N-cadherin, Vimentin) of RB cells. Bioinformatics analysis predicted that miR-34c and miR-613 targeted with 3'-UTR of DANCR, besides, miR-34c and miR-613 also targeted with 3'-UTR of MMP-9, which was validated by luciferase reporter assay. Functional experiments demonstrated that miR-34c and miR-613 could reverse the oncogenic function of DANCR in RB tumorigenesis. In conclusion, our results reveal that DANCR function as competing endogenous RNA (ceRNA) for miR-34c and miR-613 to modulate progression and metastasis in RB oncogenesis via targeting MMP-9, presenting the in-depth regulation of DANCR in RB and providing a novel insight for ceRNA mechanism for RB.

MiR-613 suppressed the laryngeal squamous cell carcinoma progression through regulating PDK1.

MicroRNAs (miRNAs) are aberrantly expressed in several tumors and play important role in tumorigenesis. However, little is known about the role of miR-613 in laryngeal squamous cell carcinoma (LSCC). We determined the expression of miR-613 in a panel of 30 LSCC specimens. Compared with the adjacent normal samples, 20 cases of LSCC tissues exhibited decreased expression of miR-613. The average expression of miR-613 in LSCC tissues was lower than in normal samples. Moreover, we demonstrated that exogenous expression of miR-613 suppressed LSCC cell proliferation, invasion, and blocked G1/S phase transition. We identified that 3-phosphoinositide-dependent protein kinase-1 (PDK1) was a direct target gene of miR-613 in LSCC cell. Overexpression of miR-613 suppressed PDK1 expression in LSCC cell. Furthermore, we demonstrated that PDK1 was upregulated in LSCC tissues. MiR-613 expression was inversely correlated with the expression of PDK1 in LSCC tissues. Moreover, we showed that PDK1 was involved in the miR-613-mediated cancer suppression of LSCC cell. These results suggested that miR-613 played as a tumor suppressor gene in LSCC partly by inhibiting PDK1 expression.

CXCR4-mediated osteosarcoma growth and pulmonary metastasis is suppressed by MicroRNA-613.

Osteosarcoma is the most common primary bone malignancy. Recently, studies showed chemokine receptor 4 (CXCR4) played a critical role in osteosarcoma. However, the regulation of CXCR4 is not fully understood. microRNAs are short, non-coding RNAs that play an important roles in post-transcriptional regulation of gene expression in a variety of diseases including osteosarcoma. miR-613 is a newly discovered miRNA and has been reported to function as a tumor suppressor in many cancers. In this study, we confirmed that both Stromal Cell-Derived Factor (SDF-1) and CXCR4 could be prognostic markers for osteosarcoma. Meanwhile this study found that SDF-1/CXCR4 pathway regulated osteosarcoma cells proliferation, migration and reduced apoptosis. Besides, we demonstrated that miR-613 was significantly downregulated in osteosarcoma patients. Elevated expression of miR-613 directly suppressed CXCR4 expression and then decreased the proliferation, migration and induced apoptosis of osteosarcoma cells. Moreover, our study found that CXCR4 promoted the development of lung metastases and inhibition of CXCR4 by miR-613 reduced lung metastases. These data indicated that CXCR4 mediated osteosarcoma cell growth and lung metastases and this effect can be suppressed by miR-613 through directly downregulating CXCR4.

WBP2 Downregulation Inhibits Proliferation by Blocking YAP Transcription and the EGFR/PI3K/Akt Signaling Pathway in Triple Negative Breast Cancer.

BACKGROUND/AIMS: Dysregulated expression of WW domain-binding protein 2 (WBP2) is associated with poor prognosis in ER+ breast cancer patients. However, its role in triple negative breast cancer (TNBC) has not been previously assessed. Therefore, we aimed to elucidate the functional mechanism of WBP2 in TNBC cells. METHODS: qRT-PCR, western blotting, and immunohistochemical staining were used to evaluate WBP2 expression in TNBC patient tumors and cell lines. HCC1937 and MDA-MB-231 cells transiently transfected with WBP2 small interfering RNA (siRNA), miR-613 mimics, or miR-613 inhibitors were subject to assays for cell viability, apoptosis and cell cycle distribution. Co-immunoprecipitation, western blotting or qRT-PCR were employed to monitor changes in signaling pathway-related genes and proteins. Luciferase assays were performed to assess whether WBP2 is a direct target of miR-613. The effect of miR-613 on tumor growth was assessed in vivo using mouse xenograft models. RESULTS: The expression of WBP2 was upregulated in TNBC tissues and cells. Expression of WBP2 was significantly correlated with Ki67 in TNBC patients. Knockdown of WBP2 inhibited cellular proliferation, promoted apoptosis, and induced cell cycle arrest of TNBC cells. miR-613 directly bound to the 3'-untranslated region (3'-UTR) of WBP2 and regulated the expression of WBP2. Moreover, miR-613 reduced the expression of WBP2 and suppressed tumor growth of TNBC cells in vivo. Knockdown of WBP2 inhibited YAP transcription and the EGFR/PI3K/Akt signaling pathway in TNBC cells, and these effects were reversed by inhibition of miR-613. CONCLUSION: WBP2 overexpression is associated with the poor prognosis of TNBC patients and the miR-613-WBP2 axis represses TNBC cell growth by inactivating YAP-mediated gene expression and the EGFR/PI3K/Akt signaling pathway.

MicroRNA-613 promotes colon cancer cell proliferation, invasion and migration by targeting ATOH1.

The aim of the present study is to investigate the expression and function of miR-613 in colon cancer (CC) and illuminate the molecular mechanisms underlying miR-613-regulated CC progression. Our data demonstrated that miR-613 was upregulated in CC tissue samples (P = 0.009) and human CC cell lines (HCT-116 and Lovo; P = 0.001 and P = 0.003, respectively), which also promoted the proliferation, invasion and migration of CC cells (P < 0.05). The dual-luciferase reporter assay confirmed that Atonal homolog1 (ATOH1) was the target mRNA of miR-613. Rescue experiments showed that ATOH1 overexpression vector significantly reversed the stimulative effects of miR-613 mimic on the progression of HCT-116 and Lovo cells (P < 0.001). Positive ATOH1 expression in CC tissues was significantly associated with lower grade (χ2 = 3.592, P = 0.043), lower TNM stage (χ2 = 3.537, P = 0.048) and better overall survival (P=0.041). Jun N-terminal kinase 1 (JNK1) pathway and Mucin 2 (MUC2) were the potential downstream proteins of miR-613/ATOH1. miR-613 is an oncogene in CC and promotes the proliferation, invasion and migration of CC cells by targeting ATOH1 likely via activating JNK1 pathway and upregulating MUC2.

MiR-613 suppresses retinoblastoma cell proliferation, invasion, and tumor formation by targeting E2F5.

Retinoblastoma is a common intraocular malignancy that occurs during childhood. MicroRNAs play critical roles in the regulation of retinoblastoma initiation and progression, and aberrant expression of miR-613 had been reported in various types of cancer. However, the role and mechanism of its function in retinoblastoma are still unclear. In this study, we found that miR-613 was downregulated in retinoblastoma tissues and cell lines. Overexpression of miR-613 suppressed retinoblastoma cell proliferation, migration, and invasion and induced cell cycle arrest in vitro. Additionally, overexpressed miR-613 also inhibited tumor formation of retinoblastoma cells in vivo. We further identified E2F5 as a direct target of miR-613. Reintroduction of E2F5 without 3'-untranslated region reversed the inhibitory effects of miR-613 on cell proliferation and invasion. Our data collectively indicate that miR-613 functions as a tumor suppressor in retinoblastoma through downregulating E2F5, supporting the targeting of the novel miR-613/E2F5 axis as a potentially effective therapeutic approach for retinoblastoma.

miR-613 inhibits proliferation and invasion of breast cancer cell via VEGFA.

MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in breast cancer, has remained elusive. Here, we identified that miR-613 inhibits breast cancer cell proliferation by negatively regulates its target gene VEGFA. In breast cancer cell lines, CCK-8 proliferation assay indicated that the cell proliferation was inhibited by miR-613, while miR-613 inhibitor significantly promoted the cell proliferation. Transwell assay showed that miR-613 mimics significantly inhibited the migration and invasion of breast cancer cells, whereas miR-613 inhibitors significantly increased cell migration and invasion. Luciferase assays confirmed that miR-613 directly bound to the 3' untranslated region of VEGFA, and western blotting showed that miR-613 suppressed the expression of VEGFA at the protein levels. This study indicated that miR-613 negatively regulates VEGFA and inhibits proliferation and invasion of breast cancer cell lines. Thus, miR-613 may represent a potential therapeutic molecule for breast cancer intervention.

MicroRNA-613 represses prostate cancer cell proliferation and invasion through targeting Frizzled7.

A growing number of studies have indicated that microRNAs (miRNAs) are critical regulators of carcinogenesis and cancer progression and may serve as potential therapeutic tools for cancer therapy. Frizzled7 (Fzd7), the most important receptor of the Wnt signaling pathway, is extensively involved in cancer development and progression. However, the role of Fzd7 in prostate cancer remains unclear. In this study, we aimed to explore the expression of Fzd7 in prostate cancer and test whether modulating Fzd7 expression by miR-613 would have an impact on prostate cancer cell proliferation and invasion. We found that Fzd7 was highly expressed in prostate cancer cell lines. Through bioinformatics analysis, Fzd7 was predicted as a target gene of miR-613, which was validated by dual-luciferase reporter assays, real-time quantitative polymerase chain reaction and Western blot analysis. By gain of function experiments, we showed that overexpression of miR-613 significantly suppressed prostate cancer cell proliferation and invasion. Furthermore, miR-613 overexpression markedly downregulated the Wnt signaling pathway. Through a rescue experiment, we showed that overexpression of Fzd7 could abrogate the inhibitory effect of miR-613 on cell proliferation and invasion as well as Wnt signaling. Additionally, these results were further strengthened by data showing that miR-613 was significantly downregulated in prostate cancer tissues, exhibiting an inverse correlation with Fzd7 expression. In conclusion, our study suggests that miR-613 functions as a tumor suppressor, partially through targeting Fzd7, and is a potential therapeutic target for prostate cancer.

MiR-613: a novel diagnostic and prognostic biomarker for patients with esophageal squamous cell carcinoma.

MicroRNA-613 (miR-613) plays important roles in tumorigenesis and cancer progression. We aimed to evaluate its expression level and potential for diagnosis and prognosis in esophageal squamous cell cancer (ESCC). We examined miR-613 expression in 60 pairs of ESCC cancerous and matched paracancerous tissues, serum samples from 75 ESCC patients and 75 healthy volunteers, and 105 formalin-fixed paraffin-embedded (FFPE) tissue samples using quantitative reverse transcription polymerase chain reaction. Receiver-operating characteristic (ROC) curve analysis, Kaplan-Meier method, and Cox regression were applied to analyze its diagnostic and prognostic value. MiR-613 was significantly decreased in ESCC tissue compared with paracancerous tissue (P < 0.001). Moreover, the expression level of miR-613 was significantly reduced with increased T stage of ESCC. Statistically significant difference between ESCC patients and healthy controls in expression level of miR-613 (0.89 ± 0.73 vs. 1.71 ± 1.03, P < 0.001) was found. The area under the ROC curve (AUC) based on serum miR-613 was 0.767 ± 0.040. We also performed analysis on early-stage patients and revealed that the AUC value was 0.728 ± 0.052 (P < 0.001). The Kaplan-Meier curve revealed that the downregulation of miR-613 was related to worse overall survival (OS) and progression-free survival (PFS) of ESCC patients (P = 0.018 and P = 0.035, respectively). Furthermore, the multivariate analysis identified miR-613 to be an independent prognostic factor for OS and PFS (P = 0.031 and P = 0.006, respectively) In conclusion, miR-613 is significantly reduced in cancerous tissue and serum samples of ESCC patients. It can serve as an ideal indicator for the diagnosis and prognosis of ESCC.

MicroRNA-613 inhibited ovarian cancer cell proliferation and invasion by regulating KRAS.

MicroRNAs (miRNAs) play several important roles in carcinogenesis, and the dysregulation of miRNAs is associated with cancer progression. Little is known about the role of miR-613 in ovarian cancer. In the present study, we demonstrate that miR-613 expression is downregulated in human ovarian cancer cell lines and tissues. Additionally, miR-613 overexpression suppressed ovarian cancer cell proliferation, colony formation, and invasion. Furthermore, KRAS was identified as a target of miR-613. Reintroducing KRAS rescued the inhibitory effects exerted by miR-613 on ovarian cancer cell proliferation and invasion. Taken together, our findings suggest that miR-613 functions as a candidate tumor suppressor miRNA in ovarian cancer by directly targeting KRAS. To the best of our knowledge, this is the first study to show that miR-613 affects the proliferation and invasion of ovarian cancer.

Knockdown of Long Noncoding RNA Urothelial Carcinoma-Associated 1 Represses Gallbladder Cancer Advancement by Regulating SPOCK1 Expression Through Sponging miR-613.

Background: Gallbladder cancer (GBC) is the most common biliary tract malignancy. Long noncoding RNA urothelial carcinoma-associated 1 (UCA1) and MicroRNA-613 (miR-613) have been reported to be involved in the progression of various cancers. However, the regulatory mechanism between UCA1 and miR-613 in GBC is unclear. Materials and Methods: The expression levels of UCA1, miR-613, and secreted protein/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1) mRNA were detected using quantitative real-time polymerase chain reaction. Cell proliferation, migration, invasion, and apoptosis were determined with MTT, transwell, or flow cytometry assays. The levels of SPOCK1 protein, Bax, cleaved-casp-3, and Bcl-2 were determined by Western blot analysis. The relationship between miR-613 and UCA1 or SPOCK1 was verified through dual-luciferase reporter and/or RNA immunoprecipitation assays. Xenograft assay was performed to verify the role of UCA1 in vivo. Results: UCA1 and SPOCK1 were upregulated, whereas miR-613 was downregulated in GBC tissues and cells. UCA1 silencing decreased tumor growth in vivo and impeded proliferation, migration, invasion, and induced apoptosis of GBC cells in vitro. Notably, UCA1 acted as a sponge for miR-613, which targeted SPOCK1 in GBC cells. Moreover, UCA1 enhancement reversed the repressive impact of miR-613 mimic on the malignancy of GBC cells. UCA1 regulated SPOCK1 expression through adsorbing miR-613. Furthermore, SPOCK1 elevation overturned UCA1 silencing mediated the malignant behaviors of GBC cells. Conclusion: UCA1 knockdown suppressed GBC progression through downregulating SPOCK1 via sponging miR-613, providing an evidence for UCA1 as a target for GBC treatment.

miR-613 suppresses renal cell carcinoma proliferation, invasion and migration by regulating the AXL/AKT pathway.

In the last few decades, microRNAs (miRNAs) are possible to effectively control and treat cancer. However, the function of miR-613 in renal cell carcinoma (RCC) is not very clear up to now. Here, the direction of this research was to investigate the influence of miR-613 for the proliferation, invasion and migration of RCC, and the underlying molecular mechanism. First, the mRNA and protein expression levels of miR-613 were determined in RCC tissues and cancer cells (786-O and ACHN). Using bioinformatics and literature review, anexelekto (AXL), as the target of miR-613 in renal cell carcinoma, was screened. Phenotype experiment and mechanism experiment illustrated the targeting relationship between miR-613 and AXL in cancer cells. Furthermore, a rescue assay with AXL overexpression was performed to make a profound study whether miR-613 disturbs RCC proliferation, invasion, and migration through direct regulation of AXL. Finally, through experiment in vivo, we observe the influence of miR-613 overexpression for tumor. These results were as follows. The present findings proved, in RCC, that the production of miR-613 was at a low level. Except for this point, this current research confirmed, in RCC cells, that the upregulation of miR-613 can control proliferation, metastasis, and invasion by reducing AXL levels and controlling the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway.