Circular RNA hsa_circ_0061395 accelerates hepatocellular carcinoma progression via regulation of the miR-877-5p/PIK3R3 axis

• Published in: Cancer cell international Vol. 21; no. 1; p. 10
• Main Authors: Yu, Yanhui, Bian, Lijuan, Liu, Renfei, Wang, Yitong, Xiao, Xia
• Format: Journal Article
• Language: English
• Published: England BioMed Central 06.01.2021; BMC
• Subjects: Apoptosis; Binding sites; Cell cycle; Cell migration; Cell proliferation; Cholecystokinin; Circular RNA; Exosomes; Flow cytometry; Gene expression; Hepatocellular carcinoma; Immunoprecipitation; Kinases; Liver cancer; MicroRNAs; miRNA; mRNA; Nanoparticles; Polymerase chain reaction; Primary Research; Proteins; Tumors; Western blotting; Xenografts; United States > US; China; Japan
• ISSN: 1475-2867; 1475-2867
• DOI: 10.1186/s12935-020-01695-w

Circular 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. The 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. Circ_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. Circ_0061395 facilitated HCC progression via regulating the miR-877-5p/PIK3R3 axis, providing a new perspective on the advancement of HCC.