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

Abstract

Background 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. Methods 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. Results 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. Conclusion Circ_0061395 facilitated HCC progression via regulating the miR-877-5p/PIK3R3 axis, providing a new perspective on the advancement of HCC.

Thymoquinone Suppresses the Proliferation, Migration and Invasiveness through Regulating ROS, Autophagic Flux and miR-877-5p in Human Bladder Carcinoma Cells

“…It is found that miR-877-5p inhibits the cell proliferation, migration and invasion of hepatoma [40] and suppresses the cell growth of gastric carcinoma [39]. Also, more researches demonstrate that various long non-coding RNAs or circular RNAs facilitate the tumorgenesis of different carcinomas by decreasing the level of miR-877-5p [66][67][68][69][70], further verifying the suppressive effect of miR-877-5p in cancer development. In accordance with previous researches, the results of our experiments showed that TQ significantly upregulated the miR-877-5p expression level, and the inhibitor of miR-877-5p markedly upregulated the mRNA levels of CD274 (PD-L1), suggesting that CD274 mRNA is the downstream target of miR-877-5p.…”

Circular RNA circCCNT2 is upregulated in the anterior cingulate cortex of individuals with bipolar disorder

“…We also identified miR-877-5p binding sites on circCCNT2. Interestingly, miR-877-5p and miR-877-3p have been reported to interact with several other circRNAs in relation to cancer progression [ 62 – 64 ]. However, this relationship has not previously been reported in the context of any neuropsychiatric disorders.…”

Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

“… 240 Expressions of exosomal circRNAs, such as circAKT3, has-circ-0004001, has-circ-0004123, has-circ-0075792, circ-0061395, and circTMEM45A are also highly upregulated in HCC patients. 241 – 243 However, exosomal circ-0051443 is downregulated in plasma exosomes from HCC patients, which exerts a role in inducing cell apoptosis and inhibiting malignant behaviors. 244 Wang et al reported that level of exosomal has-circ-0074854 is also downregulated in HCC patients and plays a role in inhibiting tumor cell migration and invasion by repressing M2 macrophage polarization.…”