Circular ribonucleic acid nei-like deoxyribonucleic acid glycosylase 3 governs the microribonucleic acid -3150b-3p/laminin subunit gamma 1 network to partially promote the development of hepatocellular carcinoma

Hepatol Res. 2021 Jun;51(6):702-714. doi: 10.1111/hepr.13636. Epub 2021 Apr 9.


Aim: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and its progression is implicated in the dysregulation of circular ribonucleic acids (RNAs). This study aimed to investigate the role of circular RNA nei-like DNA glycosylase 3 (circNEIL3) in HCC.

Methods: Real-time quantitative PCR was used for expression analysis of circNEIL3, microRNA-3150b-3p (miR-3150b-3p) and laminin subunit gamma 1 (LAMC1) message RNA. MTT assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry assay were performed for functional analyses on cell proliferation, migration, invasion, apoptosis, and cycle. The expression of marker proteins and LAMC1 protein was quantified by western blot. The interaction between miR-3150b-3p and circNEIL3 or LAMC1 was confirmed by dual-luciferase reporter assay or RNA immunoprecipitation assay. An animal study was performed to confirm the role of circNEIL3 in vivo.

Results: CircNEIL3 was upregulated in tumor tissues and HCC cell lines. CircNEIL3 knockdown significantly suppressed HCC cell proliferation, migration and invasion and induced cell apoptosis and cell cycle arrest. MiR-3150b-3p was a target of circNEIL3, and its inhibition largely reversed the functional effects of circNEIL3 knockdown on cell behaviors. Moreover, LAMC1 served as a target of miR-3150b-3p, and its expression was elevated in HCC tissues and cells. LAMC1 overexpression recovered HCC cell proliferation, migration and invasion that were blocked by miR-3150b-3p restoration. Additionally, circNEIL3 knockdown inhibited tumor growth in mice.

Conclusion: CircNEIL3 dysregulation was responsible for the partial development of HCC by regulating the miR-3150b-3p/LAMC1 regulatory network.

Keywords: HCC; LAMC1; circNEIL3; miR-3150b-3p.