Over-expression of long non-coding RNA insulin-like growth factor 2-antisense suppressed hepatocellular carcinoma cell proliferation and metastasis by regulating the microRNA-520h/cyclin-dependent kinase inhibitor 1A signaling pathway.

Abstract

Primary liver cancer is the sixth most common cancer and the third leading cause of malignancy-related death worldwide in 2020, with 75-85% of hepatocellular carcinoma (HCC). Evidences have verified that long noncoding RNAs (lncRNAs) play key roles in HCC onset and development. However, the function and mechanism of lncRNA insulin-like growth factor 2-antisense (IGF2-AS) in HCC remain unclear. Herein, IGF2-AS expression profile in HCC patients was first investigated based on The Cancer Genome Atlas (TCGA) database and local HCC patients, followed by prognostic value evaluation using Kaplan-Meier method; then, the bioinformatics analysis, dual-luciferase reporter assay, Spearman correlation assay, function gain, and loss with rescue experiments were applied to investigate the biological function and the involved molecular mechanisms of IGF2-AS in HCC oncogenesis and development. Our results showed that IGF2-AS expression was significantly down-regulated in HCC cells and tissues; lower IGF2-AS expression was significantly associated with poor prognosis of HCC patients; IGF2-AS over-expression inhibited the viability, colony formation, invasion, and migration, while promoted apoptosis in vitro, and inhibited HCC xenograft growth in vivo; IGF2-AS sponged microRNA-520h (miR-520h) to up-regulate IGF2-AS expression, and miR-520h over-expression or cyclin-dependent kinase inhibitor 1A (CDKN1A) silencing reversed IGF2-AS reduced aggressive behaviors of HCC cells. In conclusion, IGF2-AS is a tumor-suppressor in HCC, and lower IGF2-AS expression is associated with poor prognosis of HCC patients; IGF2-AS inhibits HCC oncogenesis and development by IGF2-AS/miR-520h/CDKN1A pathway. Therefore, IGF2-AS may serve as a new biomarker for HCC management.

• Authors: Zhen Huang, Guofeng Su, Xiaoxia Bi, Libo Zhang, Zhuohui Xu, Ge Wang
• Journal: Bioengineered (Bioengineered) Vol. 12 Issue 1 Pg. 6952-6966 (12 2021) ISSN: 2165-5987 [Electronic] United States
• PMID: 34516353 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• IGF2-AS lncRNA, human
• MIRN520 microRNA, human
• MicroRNAs
• Proteins

Topics

• Carcinoma, Hepatocellular (genetics, metabolism, mortality, pathology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics, metabolism)
• Female
• Humans
• Liver (pathology)
• Liver Neoplasms (genetics, metabolism, mortality, pathology)
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Proteins (genetics, metabolism)
• Signal Transduction (genetics)
• Transcriptome (genetics)