Circular RNA circUBE2J2 acts as the sponge of microRNA-370-5P to suppress hepatocellular carcinoma progression

Abstract

Accumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in hepatocellular carcinoma is largely unknown. CircRNA microarray was performed to identify abnormally expressed circRNAs in HCC tissue samples. We conducted Kaplan–Meier survival analysis to explore the significance of circUBE2J2 in clinical prognosis. Then, we examined the functions of circUBE2J2 in HCC by cell proliferation, migration, and mouse xenograft assay. We identified miR-370-5P as a circUBE2J2-related microRNA by using biotin-labeled circUBE2J2 probe to perform RNA antisense purification (RAP) assay in HCC cells. The dual luciferase reporter assay and RNA pulldown assays were employed to verify the relationships among circUBE2J2, miRNA-370-5P, and KLF7. Microarray analysis and qRT-PCR verified a circRNA termed circUBE2J2 that was downregulated in HCC. Kaplan–Meier survival analysis showed that downregulated circUBE2J2 was correlated with poorer survival. CircUBE2J2 expression in HCC cells was selectively regulated via luciferase reporter assays; circUBE2J2 and KLF7 were observed to directly bind to miR-370-5P. Furthermore, knockdown of circUBE2J2 in HCC could downregulate KLF7, the target of miR-370-5P, thus promoting the proliferation and migration of HCC cells. Then the related experiment suggested that circUBE2J2 could regulate the expression of KLF7 by sponging miR-370-5p. In summary, we infer that circUBE2J2 may act as a competing endogenous RNA (ceRNA) to regulate KLF7 expression through sponging miR-370-5P and play a regulatory functions in HCC. CircUBE2J2 may be a diagnostic biomarker and potential target for HCC therapy.

Silencing of lncRNA CHRM3-AS2 Expression Exerts Anti-Tumour Effects Against Glioma via Targeting microRNA-370-5p/KLF4

“…In this study, miR-370-5p was identified as a target of CHRM3-AS2 in glioma. miR-370-5p is an anti-oncogene that has been reported to be down-regulated in breast, lung, liver, and ovarian cancers (20)(21)(22)(23). Decreased expression of miR-370-5p was consistently observed in glioma cells.…”

“…Li et al found that overexpression of miR-370-5p inhibits cell proliferation, migration, and invasion and induces cell-cycle arrest in nonsmall-cell lung carcinoma cells (21). Zhang et al (22) revealed that knockdown of miR-370-5p enhances the proliferative and invasive rates of colorectal cancer cells. As miR-370-5p expression is downregulated by CHRM3-AS2, we suspect that the anti-tumour effect of CHRM3-AS2 silencing in glioma cells is associated with the upregulation of miR-370-5p expression.…”

“…Zhang et al. ( 22 ) revealed that knockdown of miR-370-5p enhances the proliferative and invasive rates of colorectal cancer cells. As miR-370-5p expression is down-regulated by CHRM3-AS2, we suspect that the anti-tumour effect of CHRM3-AS2 silencing in glioma cells is associated with the up-regulation of miR-370-5p expression.…”

“…These targets include miR-451 ( 15 ), -93 ( 16 ), -320a ( 17 ), -27b-3p ( 18 ), and -6869-5p ( 19 ). miR-370-5p serves as an anti-oncogene in breast cancer ( 20 ), lung cancer ( 21 ), hepatocellular carcinoma ( 22 ), and ovarian cancer ( 23 ). However, the functions of miR-370-5p in glioma and related mechanisms have not been explored.…”

Circ_0005526 contributes to interleukin-1β-induced chondrocyte injury in osteoarthritis via upregulating transcription factor 4 by interacting with miR-142-5p

“… CircRNAs are implicated in disease development via sponging miRNAs. For instance, circUBE2J2 reduced migration and proliferation of hepatocellular carcinoma cells via controlling miR-370-5p [ 26 ]. CircRNA ubiquitin-specific protease 34 (circUSP34) exacerbated cell malignant behaviors of osteosarcoma by inhibiting miR-16-5p [ 27 ].…”