Use of miRNA Sequencing to Reveal Hub miRNAs and the Effect of miR-582-3p/SMAD2 in the Progression of Hepatocellular Carcinoma

Yi Zhao; Meizhang Li; Nana Miao; Wei Wei; Yulong Dong; Chenjie Tao; Jinzhong Chen; Yongyan Pei; Lieping Guo

doi:10.3389/fgene.2022.819553

Use of miRNA Sequencing to Reveal Hub miRNAs and the Effect of miR-582-3p/SMAD2 in the Progression of Hepatocellular Carcinoma

Front Genet. 2022 Mar 21:13:819553. doi: 10.3389/fgene.2022.819553. eCollection 2022.

Authors

Yi Zhao¹, Meizhang Li², Nana Miao², Wei Wei², Yulong Dong², Chenjie Tao², Jinzhong Chen³, Yongyan Pei⁴, Lieping Guo²

Affiliations

¹ Department of Gastrointestinal Endoscopy, Eastern Hepatobiliary Surgery Hospital,The Third Hospital Affiliated of Naval Medical University, Shanghai, China.
² Department of Oncology/Hematology, Eastern Hepatobiliary Hospital, Third Affiliated Hospital of Navy Military Medical University, Shanghai, China.
³ State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
⁴ School of Medicine and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, China.

Abstract

Hepatocellular carcinoma is a common tumor with a high fatality rate worldwide, and exploring its pathogenesis and deterioration mechanism is a focus for many researchers. Increasing evidence has shown that miRNAs are involved in the occurrence and progression of a variety of cancers, including hepatocellular carcinoma. Therefore, this study mainly aimed identify key miRNAs related to hepatocellular carcinoma and explore their potential functions and clinical significance. In this study, we performed miRNA sequencing on three pairs of hepatocellular carcinoma tissue samples and screened 26 differentially expressed miRNAs. Then 2 key miRNAs (miR-139-5p and miR-582-3p) were screened by Kaplan-Meier curve analysis, Cox multivariate analysis and qPCR methods. The expression of miR-582-3p was positively correlated with clinicopathological parameters in patients with hepatocellular carcinoma. Subsequently, miRwalk and starbase were used to predict the target genes of key miRNAs, and then the key pairs miR-582-3p/SMAD2 identified by WGCNA, PPI, qPCR and Pearson correlation analysis. Finally, a dual luciferase experiment, the rescue-of-function experiment and qPCR confirmed that miR-582-3p directly targets SMAD2 and regulates the proliferation, migration and invasion of HepG2 cells by targeting SMAD2. At the same time, interference with SMAD2 can influence the effect of miR-582-3p on HepG2 cells. In conclusion, our findings confirm that miR-582-3p is an independent factor for the prognosis of hepatocellular carcinoma patients, and can regulate the progression of hepatocellular carcinoma cells by targeting SMAD2.

Keywords: hepatocellular carcinoma; miR-582-3p/SMAD2; miRNA sequencing; migration and invasion; proliferation.