Circular RNA hsa_circ_0000144 aggravates ovarian Cancer progression by regulating ELK3 via sponging miR-610.

BACKGROUND: Ovarian cancer is a common cause of death among women and a health problem worldwide. Circ_0000144 has been confirmed to be an oncogene involved in cancer progression, such as gastric cancer. However, the role of circ_0000144 in ovarian cancer remains unclear and needs to be elucidated. This retrospective study aimed to investigate the underlying mechanism of circ_0000144 in ovarian cancer. METHODS: Differentially expressed circ_0000144 expression in ovarian cancer and normal tissues was identified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). In vitro assays were performed to explore the biological functions of circ_0000144 in ovarian cancer cells. An in vivo xenograft model was used to investigate the efficacy of circ_0000144 in the progression of ovarian cancer. RESULTS: Circ_0000144 was significantly upregulated in ovarian cancer cells and tissues. Circ_0000144 overexpression significantly promoted ovarian cancer cell proliferation, migration, and invasion. This study further demonstrated that circ_0000144 downregulated ELK3 levels by sponging miR-610 in ovarian cancer cells. Moreover, circ_0000144 significantly promotes ovarian cancer tumorigenesis in vivo. CONCLUSION: Our data indicate that circ_0000144 could enhance the carcinogenesis of ovarian cancer by specifically targeting miR-610, which may serve as a novel target for the diagnosis and prognosis of ovarian cancer.

Upregulation of circ_0000142 promotes multiple myeloma progression by adsorbing miR-610 and upregulating AKT3 expression.

Circular RNAs (circRNAs) play an important regulatory role in a variety of malignancies. Nevertheless, the role of circ_0000142 in multiple myeloma (MM) and its regulatory mechanism remains largely unknown. Real-time polymerase chain reaction was employed to detect the expressions of circ_0000142 and miR-610 in MM tissues and cell lines. The expression of AKT3 and apoptosis-related proteins (Bcl-2, Bax) in MM cells was detected by western blot. The correlation between the expression level of circ_0000142 and the clinicopathological parameters of MM patients was analysed. Cell proliferation, apoptosis, migration and invasion were monitored by Cell Counting Kit 8 assay, flow cytometry analysis and Transwell assay, respectively. The dual-luciferase reporter gene assay and RNA immunoprecipitation assay were employed to verify the targeting relationship between circ_0000142 and miR-610. In this study, it was demonstrated that, circ_0000142 was highly expressed in MM patients, and its high expression level was significantly associated with increased International Staging System and Durie-Salmon stage. Overexpression of circ_0000142 enhanced MM cell proliferation, migration, invasion and suppressed cell apoptosis, while knocking down circ_0000142 had the opposite effects. Mechanistically, circ_0000142 functioned as a competitive endogenous RNA, directly targeting miR-610 and positively regulating AKT3 expression. In brief, circ_0000142 enhances the proliferation and metastasis of MM cells by modulating the miR-610/AKT3 axis.

Exosomal lncRNA CHL1-AS1 Derived from Peritoneal Macrophages Promotes the Progression of Endometriosis via the miR-610/MDM2 Axis.

BACKGROUND: Exosomes secreted by peritoneal macrophages (pMφ) are deeply involved in the development of endometriosis (EMs). Exosomes can mediate cell-to-cell communication by transferring biological molecules. This study aimed to explore the effect and mechanism of exosomal long non-coding RNA (lncRNA) CHL1-AS1 derived from pMφ on EMs. MATERIALS AND METHODS: Exosomes (exo) from pMφ were isolated, identified, and co-cultured with ectopic endometrial stromal cells (eESCs) to investigate the biological functions of pMφ-exo. qRT-PCR was used to detect the expression of lncRNA CHL1-AS1 in pMφ-exo from EMs and control patients and verify the transportation of lncRNA CHL1-AS1 from pMφ to eESCs. The effects of exosomal lncRNA CHL1-AS1 on eESC proliferation, migration, invasion, and apoptosis were also detected. The relationships among lncRNA CHL1-AS1, miR-610, and MDM2 (mouse double minute 2) were verified by dual-luciferase reporter assay. The in vivo experiments were conducted to verify the effects of exosomal lncRNA on EMs using a xenograft model of EMs. RESULTS: Exosomes from pMφ were successfully isolated. EMs-pMφ-exo promoted eESC proliferation, migration, and invasion and inhibited their apoptosis. lncRNA CHL1-AS1 was upregulated in EMs-pMφ-exo and transported from pMφ to eESCs via exosomes. lncRNA CHL1-AS1 was found to act as a competing endogenous RNA of miR­610 to promote the expression of MDM2. EMs-pMφ-exo shuttled lncRNA CHL1-AS1 to promote eESC proliferation, migration, and invasion and inhibit apoptosis by downregulating miR-610 and upregulating MDM2. Furthermore, exosomal lncRNA CHL1-AS1 promoted EMs lesions growth by increasing MDM2 in vivo. CONCLUSION: The results demonstrate that exosomal lncRNA CHL1-AS1 promotes the proliferation, migration, and invasion of eESCs and inhibits their apoptosis by downregulating miR-610 and upregulating MDM2, which might be a potential therapeutic target for EMs.

Circ_0015756 Aggravates Hepatocellular Carcinoma Development by Regulating FGFR1 via Sponging miR-610.

BACKGROUND: Hepatocellular carcinoma (HCC) is the leading threat of cancer-related death in humans. Increasing studies show that circular RNAs (circRNAs) are important indicators in cancer diagnosis and prognosis. This study intended to explore the function and mechanism of circ_0015756 in HCC, providing the additional opinion for HCC treatment. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of circ_0015756 and miR-610. Cell viability was assessed by cell counting kit-8 (CCK-8) assay, and colony formation capacity was ascertained by colony formation assay. Cell migration and invasion were monitored by transwell assay. Cell cycle progression and apoptosis were analyzed by flow cytometry assay. Circ_0015756 oncogenicity was determined by Xenograft models. The targets of circ_0015756 and miR-610 were predicted by bioinformatics tools and validated using RNA pull-down, RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. The expression level of fibroblast growth factor receptor 1 (FGFR1) was measured by Western blot. RESULTS: The expression of circ_0015756 was increased in HCC tissues, serums and cells. Circ_0015756 downregulation impaired HCC cell viability, colony formation capacity, invasion and migration, induced cell cycle arrest and apoptosis, and inhibited tumor growth in vivo. MiR-610 was ensured as a target of circ_0015756, and miR-610 absence reversed the effects of circ_0015756 downregulation. Further, FGFR1 was targeted by miR-610, and FGFR1 overexpression overturned the effects of miR-610 restoration in HCC cells. Circ_0015756 could regulate FGFR1 expression by targeting miR-610. CONCLUSION: Circ_0015756 played its tumorigenic properties in HCC by activating FGFR1 via sponging miR-610, and circ_0015756 was expected to be a vital indicator in HCC diagnosis and treatment.

Circular RNA MAT2B Induces Colorectal Cancer Proliferation via Sponging miR-610, Resulting in an Increased E2F1 Expression.

PURPOSE: Recently, studies have demonstrated that a novel circular RNA (circRNA), circMAT2B, can promote cell proliferation and can thus contribute to the growth and development of hepatocellular carcinoma. However, the precise mechanisms underlying in circMAT2B-induced colorectal cancer (CRC) cell proliferation are not yet fully understood. MATERIALS AND METHODS: Quantitative reverse transcription polymerase chain reaction was conducted to evaluate circMAT2B expression in 70 CRC tissues and 70 matched adjacent normal tissues, CRC cell lines and human colonic epithelial cell line (NCM460). The direct interaction between miR-610 and circMAT2B or E2F1 was verified using luciferase reporter assay and biotinylated RNA Pull-down assay. Cell Counting Kit-8, colony formation assay, flow cytometry were utilized to examine the effect of circMAT2B, miR-610 and E2F1 on cell proliferation. Western blot was conducted to evaluate E2F1 expression. RESULTS: In our study, circMAT2B was found to be upregulated in CRC tissues and cell lines. Furthermore, the silencing of circMAT2B significantly inhibited proliferation. Hence, in order to investigate the mechanism underlying the oncogenic properties of circMAT2B in CRC, a bioinformatics analysis (circular RNA Interactome, https://circinteractome.nia.nih.gov/) was performed to screen the putative interacting microRNAs of circMAT2B. miR-610 was identified to be one of the potential targeted miRNAs of circMAT2B. Luciferase reporter and RNA pulldown assay confirmed a direct interaction between circMAT2B and miR-610. Moreover, circMAT2B expression was negatively correlated with the expression of miR-610 in CRC tissues (r=-0.5131, p<0.0001). Furthermore, we demonstrated circMAT2B upregulated expression levels of the miR-610 target gene E2F1, which is involved in cell proliferation, is overexpression in a broad range of human cancer including CRC. Further studies suggested that E2F1 upregulation could significantly reverse the si-circMAT2B-mediated inhibition of proliferation. CONCLUSION: circMAT2B is upregulated in CRC tissues and cell lines. Moreover, circMAT2B promoted CRC proliferation by regulating the miR-610/E2F1 axis, which may serve as a potential therapeutic target for CRC treatment.

Long non-coding RNA FEZF1-AS1 promotes cell growth in multiple myeloma via miR-610/Akt3 axis.

Increasing evidence showed that long non-coding RNAs (lncRNAs) play critical roles in tumor progression. FEZF1-AS1 is a cancer-associated lncRNA which upregulated and associated with poor prognosis in patients with cancer. However, the roles of FEZF1-AS1 in multiple myeloma (MM) remains unclear. In the present study, our data revealed that FEZF1-AS1 expression was increased both in MM samples and cell lines. Loss of functional assays indicated that FEZF1-AS1 suppression inhibited MM cells proliferation, arrested cell cycle in G0/G1 phase and induced cell apoptosis in vitro. Furthermore, our data indicated that FEZF1-AS1 functioned as a competing endogenous RNA in MM cells that regulated miR-610 expression, which suppressed Akt3. Those data showed that FEZF1-AS1 promoted MM cells proliferation through regulating miR-610/Akt3 axis, suggesting FEZF1-AS1 could be served as a potential target for cancer therapeutics in MM.

MicroRNA-610 suppresses osteosarcoma oncogenicity via targeting TWIST1 expression.

Osteosarcoma is the most frequent primary bone tumor affects adolescents and young adults. Recently, microRNAs (miRNAs) are short, non-coding and endogenous RNAs that played as important roles in the initiation and progression of tumors. In this study, we try to explore the biological function and expression of miR-610 in the osteosarcoma. We showed that miR-610 expression was downregulated in the osteosarcoma tissues and cell lines. Elevated expression of miR-610 suppressed the osteosarcoma cell proliferation, cell cycle, invasion and EMT program. Moreover, overexpression of miR-610 increased sensitivity of MG-63 and U2OS cells to cisplatin. Twist1 was identified as a direct target gene of miR-610 in the osteosarcoma cell. Furthermore, we demonstrated that Twist1 was upregulated in the osteosarcoma tissues and cell lines. The expression of Twist1 was negatively associated with the expression of miR-610 expression in the osteosarcoma tissues. Ectopic expression of Twist1 inhibited the sensitivity of miR-610-overexpressing MG-63 cells to cisplatin. We also showed that overexpression of Twist1 increased the proliferation and invasion of miR-610-overexpressing MG-63 cells. These data indicated that ectopic expression of miR-610 suppressed the osteosarcoma cell proliferation, cell cylce, invasion and increased the sensitivity of osteosarcoma cells to cisplatin through targeting the Twist1 expression.

MiR-610 inhibits cell proliferation and invasion in colorectal cancer by repressing hepatoma-derived growth factor.

MicroRNAs (miRNAs) act as key regulators of gene expression and their dysregulation is linked to carcinogenesis and tumor progression. MiR-610 has been implicated as an anti-tumor miRNA in multiple types of cancers. However, its biological role and the underlying mechanism in colorectal cancer (CRC) have not been well explored. In this study, we report that miR-610 expression is decreased in CRC samples while ectopic expression of miR-610 suppresses cell proliferation, migration and invasion, and influences the expression of epithelial-mesenchymal transition (EMT)-associated proteins by up-regulating E-cadherin expression and down-regulating vimentin expression. Using a luciferase reporter assay, we reveal that miR-610 directly targets hepatoma-derived growth factor (HDGF) by binding to its 3'UTR. A negative correlation was also observed between miR-610 and HDGF expression in CRC tissues. Further studies show that inhibition of HDGF recapitulates the anti-tumor function of miR-610, whereas re-expression of HDGF partially abrogates the inhibitory effects of miR-610. Collectively, our findings indicate that miR-610 exerts its function by directly targeting HDGF. The miR-610/HDGF axis is a novel therapeutic target for CRC.