Transcriptome alterations in HepG2 cells induced by shRNA knockdown and overexpression of TMEM2 gene

Abstract

Transmembrane 2 (TMEM2) gene inhibits chronic hepatitis-B virus (HBV) infection, while the underlying molecular mechanisms remain unknown. Transcriptome alterations in HepG2 cells following TMEM2 overexpression or silencing by shRNA were analyzed by next-generation sequencing. Both overexpression and knockdown of the TMEM2 gene caused wide-spread changes in gene expression in HepG2 cells. Differentially expressed genes caused by altered TMEM2 gene expression were associated with multiple biological processes linked with viral infection and various signaling pathways. KEGG analysis revealed that many of the differentially expressed genes were enriched in the PI3K/AKT signaling pathway. Moreover, we show that genes related to the PI3K/AKT signaling pathway, such as SYK, FLT4, AKT3, FLT1, and IL6, are biological targets regulated by TMEM2 in HepG2 cells. This is the first transcriptome-wide study in which TMEM2-regulated genes in HepG2 cells have been screened. Our findings elucidate the molecular events associated with TMEM2-mediated hepatocyte pathogenesis in chronic HBV infection.

The spleen tyrosine kinase (SYK): A crucial therapeutic target for diverse liver diseases

“…In addition, the activation of SYK also can be positively regulated by CD81, a member of the tetraspanin protein family, which promotes the development of hepatocellular carcinomas ( Figure 2 F). In recent years, some studies also indicated that SYK joins in the regulation of PI3K/Akt signaling pathway, which hold a key role in CX3CL1-induced platelet migration as well as cell apoptosis in human hepatocellular carcinomas [ 63 , 64 ]. Totally, the accurate position of SYK in hepatocellular carcinomas is still in controversial although some SYK inhibitors have showed the therapeutic effect against human hepatocarcinogenesis.…”

Hox transcript antisense RNA knockdown inhibits osteosarcoma progression by regulating the phosphoinositide 3-kinase/AKT pathway through the microRNA miR-6888-3p/spleen tyrosine kinase axis

“…Growing evidence suggests that PI3K/AKT signaling directly or indirectly regulates important epigenetic modifications and is involved in the PI3K cascade-related tumorigenicity in cancer [ 20 ]. HOTAIR and SYK have been revealed to be the regulators of the PI3K/AKT pathway in adenocarcinoma of esophagogastric junction and HepG2 cells [ 21 , 22 ]. Therefore, the effect of the HOTAIR/miR-6888-3p/SYK axis on the PI3K/AKT pathway warrants further study.…”