Repressing phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma by microRNA-142-3p restrains the progression of hepatocellular carcinoma

Chuanli Zeng; Gang Yuan; Yaoren Hu; Donghui Wang; Xiaojun Shi; Dedong Zhu; Airong Hu; Yina Meng; Jialin Lu

doi:10.1080/21655979.2021.2020549

Repressing phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma by microRNA-142-3p restrains the progression of hepatocellular carcinoma

Bioengineered. 2022 Jan;13(1):1491-1506. doi: 10.1080/21655979.2021.2020549.

Authors

Chuanli Zeng¹, Gang Yuan^{2

3

4}, Yaoren Hu⁵, Donghui Wang², Xiaojun Shi⁵, Dedong Zhu⁵, Airong Hu⁶, Yina Meng⁷, Jialin Lu⁷

Affiliations

¹ Department of Severe Liver Disease, Ningbo HuaMei Hospital, University of Chinese Academy of Science, Ningbo, Zhejiang, China.
² Department of Acute Infection, Ningbo Huamei Hospital, University of Chinese Academy of Science, Ningbo, Zhejiang, China.
³ Ningbo Institute of Life and Health Industry, University of Chinese Academy of Science, Ningbo, Zhejiang, China.
⁴ Key Laboratory of Diagnosis and Treatment of Digestive System, Tumors of Zhejiang Province, China.
⁵ Department of Hepatology, Ningbo Huamei Hospital, University of Chinese Academy of Science, Ningbo, Zhejiang, China.
⁶ Institute of Liver Disease, Ningbo Huamei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China.
⁷ Medical School of Ningbo University, Ningbo, Zhejiang, China.

Abstract

This paper probes the mechanisms underlying miR-142-3p's modulation of hepatocellular carcinoma (HCC) invasion and apoptosis. Quantitative real-time PCR and Western blot monitored the miR-142-3p profile in HCC tissues and non-tumor tissues. The correlation between miR-142-3p expression and HCC patients' clinicopathological indicators was analyzed. miR-142-3p overexpression and knockdown models were established in HCC cell lines. Cell proliferation was gauged by the colony formation assay and BrdU staining. For measuring apoptosis, flow cytometry and Western blot were implemented. Transwell assay tested cell migration and invasion. miR-142-3p mimics or inhibitors were transfected in Huh7 and HCCLM3 cells. The targeting association between miR-142-3p and PIK3CG was predicted through bioinformatics and further verified by related experiments. The influence of PIK3CG overexpression on miR-142-3p's role in HCC was assayed. A xenografted tumor model was built in mice to validate miR-142-3p knockdown's influence on HCC in vivo. As a result, miR-142-3p exhibited a decreased profile in HCC tissues and cells. Overexpressing miR-142-3p accelerated apoptosis and suppressed the PI3K/AKT/HIF-1α signal. Knocking down miR-142-3p presented opposite effects. PIK3CG overexpression dampened the anti-tumor effect of miR-142-3p. miR-142-3p repressed HCC invasion and intensified apoptosis to restrain HCC by abating the PIK3CG-mediated PI3K/AKT/HIF-1α pathway.

Keywords: Mir-142-3p; apoptosis; hepatocellular carcinoma; pik3cg.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Carcinoma, Hepatocellular / drug therapy*
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor
Cell Movement
Cell Proliferation
Class Ib Phosphatidylinositol 3-Kinase / drug effects
Class Ib Phosphatidylinositol 3-Kinase / genetics*
Female
Gene Expression Regulation, Neoplastic / drug effects
Gene Knockdown Techniques
Humans
Liver Neoplasms / drug therapy*
Liver Neoplasms / genetics
Liver Neoplasms / pathology
Male
Mice
MicroRNAs / genetics*
RNA, Small Interfering / administration & dosage*
RNA, Small Interfering / pharmacology
Xenograft Model Antitumor Assays

Substances

MIRN142 microRNA, human
MicroRNAs
RNA, Small Interfering
Class Ib Phosphatidylinositol 3-Kinase
PIK3CG protein, human

Grant support

This work was supported by Ningbo Natural Science Foundation(Grant No. 2019A610216), Medical and Health Project of Zhejiang Province (Grant No. 2019KY179), Zhejiang provincial and municipal key medical discipline project (2016-7).