The SNHG1-Centered ceRNA Network Regulates Cell Cycle and Is a Potential Prognostic Biomarker for Hepatocellular Carcinoma

The SNHG1-Centered ceRNA Network Regulates Cell Cycle and Is a Potential Prognostic Biomarker for Hepatocellular Carcinoma

Lin Zhou,^1,2 Qing Zhang,^1,3 Haibin Deng,^1,4 Shuobo Ou,^1,4 Ting Liang^1,4 and Jianlin Zhou^1,4

¹State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, Hunan, China
²College of Clinical Laboratory, Changsha Medical University, Changsha, Hunan, China
³Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China
⁴Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Science, Hunan Normal University, Changsha, Hunan, China

Hepatocellular carcinoma (HCC) is one of the most common and lethal types of cancer. This study aimed to identify the expression regulatory network and a prognostic signature of HCC. RNA-seq data from The Cancer Genome Atlas were used to identify the differentially expressed genes (DEGs) between HCC and normal liver tissues. DEGs were subjected to the construction of protein-protein interaction (PPI) network and enrichment analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. The results showed that most of the DEGs were enriched in the cell cycle pathway, and the top 10 hub genes in the PPI network belong to the cell cycle pathway. A ceRNA network was constructed using starBase database, including one lncRNA (SNHG1), seven miRNAs (miR-195-5p, miR-199a-3p, miR-199a-5p, miR-199b-3p, miR-383-5p, miR-424-5p and miR-654-3p) and six of the top 10 hub genes (BUB1, CCNA2, CCNB1, KIF11, NCAPG, and TOP2A). In vitro experiments showed that knockdown of SNHG1 in the HCC cell lines (Huh7 and HepG2) decreased the expression of the six hub genes and cell viability, leading to cell cycle arrest at the G1 phase. These findings indicate that SNHG1 promotes cell proliferation by regulating cell cycle-related genes as a ceRNA. Additionally, Kaplan-Meier’s survival and multivariate Cox regression analysis identified a prognostic signature of seven genes (including SNHG1 and the six SNHG1-regulated hub genes) for overall survival of HCC patients. In conclusion, this study identified a novel regulatory network in HCC and a potential independent prognostic factor for overall survival of HCC patients.

Keywords —— cell cycle; ceRNA; hepatocellular carcinoma; lncRNA; SNHG1

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Tohoku J. Exp. Med 2022, 258, 265-276.

Correspondence: Jianlin Zhou, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, China.

e-mail: jlzhou@hunnu.edu.cn