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The overexpression of GRASP might inhibit cell proliferation and invasion in hepatocellular carcinoma
Author(s) -
Cheng Yang,
Yin Baobing,
Hou Tianlu,
Chen Tianyang,
Ping Jian
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28285
Subject(s) - hepatocellular carcinoma , grasp , cancer research , cell growth , microbiology and biotechnology , cell , hepatic carcinoma , biology , chemistry , computer science , genetics , programming language
This study aimed to validate the methylation of key genes in hepatocellular carcinoma (HCC) screened by bioinformatics analysis and explore whether they affected HCC cell proliferation, migration, and invasion. Using The Cancer Genome Atlas (TCGA) database, HCC‐related differentially methylated positions (DMPs) were screened, genes corresponding to DMPs were selected, and prognosis‐related genes were identified. A representative DMP was used to divide the DMPs into hyper‐ and hypomethylated groups. Expression of key genes in cell lines was detected using quantitative real‐time polymerase chain reaction and western blot analysis. After treatment of HepG2 cells with 5‐Aza‐2′ ‐ deoxycytidine (5‐Aza‐DC), gene expression was observed. Bisulfite sequencing PCR assay was used to detect methylation frequency. Overexpressed GRASP lentiviral vectors were constructed to analyze their influence on cell proliferation, migration, and invasion using cell counting kit‐8 and transwell assays. Forty‐three HCC prognosis‐related genes were screened using the TCGA database. cg00249511 (SCT) was used to divide the DMPs into hyper‐ and hypomethylated groups, distinguishing between high‐ and low‐risk samples. The prognosis survival model constructed using 12 genes revealed the prognosis type. GRASP messenger RNA was downregulated in HepG2 and upregulated after 5‐Aza‐DC treatment. In HCC tissues, methylation frequency of GRASP was upregulated. GRASP overexpression inhibited HepG2 cell proliferation, invasion, and G‐CSFR expression. Thus, GRASP might be a prognosis‐related gene controlled by methylation.