Abstract
BackgroundCircular RNA hsa_circ_0061395 (circ_0061395) has been reported to accelerate the advancement of hepatocellular carcinoma (HCC). However, the regulatory mechanism by which circ_0061395 modulates the progression of HCC is unclear.MethodsThe morphology and size of exosomes were analyzed by transmission electron microscope (TEM) and nanoparticle-tracking analysis (NTA). Protein levels were detected by western blotting. Expression levels of circ_0061395, microRNA (miR)-877-5p, and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) mRNA were assessed by quantitative real time polymerase chain reaction (qRT-PCR). The proliferation, invasion, migration, cell cycle progression, and apoptosis were analyzed by cell counting kit-8 (CCK-8), plate clone, transwell, or flow cytometry assays. The targeting relationship between circ_0061395 or PIK3R3 and miR-877-5p was verified using the dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. Xenograft assay was performed to confirm the biological function of circ_0061395 in HCC.ResultsCirc_0061395 was upregulated in HCC tissues, serum, cells, and serum-derived exosomes. Circ_0061395 silencing decreased tumor growth in vivo, and induced cell cycle arrest, apoptosis, repressed proliferation, invasion, and migration of HCC cells in vitro. MiR-877-5p was downregulated while PIK3R3 was upregulated in HCC. Circ_0061395 regulated PIK3R3 expression via competitively binding to miR-877-5p. MiR-877-5p inhibitor overturned circ_0061395 knockdown-mediated influence on malignant behaviors of HCC cells. PIK3R3 overexpression reversed the suppressive influence of miR-877-5p mimic on malignant behaviors of HCC cells.ConclusionCirc_0061395 facilitated HCC progression via regulating the miR-877-5p/PIK3R3 axis, providing a new perspective on the advancement of HCC.
Highlights
Liver cancer ranks fourth among cancer-related death causes globally [1]
Phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) served as a target for miR-877-5p in hepatocellular carcinoma (HCC) cells
Some circRNAs can act as competing endogenous RNAs and regulate gene expression by interacting with microRNAs [7]
Summary
Hepatocellular carcinoma (HCC) is one of the most common pathological types of primary liver cancer, accounting for about 85% of all liver cancer cases [2]. Studying the underlying molecular mechanisms of HCC advancement can provide potential strategies for the treatment of HCC. Some circRNAs can act as competing endogenous RNAs (ceRNAs) and regulate gene expression by interacting with microRNAs (miRs) [7]. It was reported that circ_0061395 facilitated HCC progression via inhibiting p27 expression [10]. The molecular mechanism that circ_0061395 promotes HCC progression has not been fully explained. Circular RNA hsa_circ_0061395 (circ_0061395) has been reported to accelerate the advancement of hepatocellular carcinoma (HCC). The regulatory mechanism by which circ_0061395 modulates the progression of HCC is unclear
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