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

Xiuhua Jia; Zhishuo Mo; Qiyi Zhao; Tiancheng Bao; Wexiong Xu; Zhiliang Gao; Liang Peng; Xiang Zhu

doi:10.1080/09168451.2020.1756733

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

Biosci Biotechnol Biochem. 2020 Aug;84(8):1576-1584. doi: 10.1080/09168451.2020.1756733. Epub 2020 Apr 23.

Authors

Xiuhua Jia¹, Zhishuo Mo^{2

3

4}, Qiyi Zhao^{2

3

4}, Tiancheng Bao¹, Wexiong Xu^{2

3

4}, Zhiliang Gao^{2

3

4}, Liang Peng^{2

3

4}, Xiang Zhu^{2

3

4}

Affiliations

¹ Department of Ophthalmology, Third Affiliated Hospital of Sun Yat-Sen University , Guangzhou, Guangdong Province, China.
² Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University , Guangzhou, Guangdong Province, China.
³ Guangdong Provincial Key Laboratory of Liver Diseases, Third Affiliated Hospital of Sun Yat-Sen University , Guangzhou, Guangdong Province, China.
⁴ Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University , Guangzhou, Guangdong Province, China.

PMID: 32326855
DOI: 10.1080/09168451.2020.1756733

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.

Keywords: HepG2; PI3K/AKT signaling pathway; TMEM2; hepatitis-B virus.

MeSH terms

Gene Expression Profiling
Gene Expression Regulation
Hep G2 Cells
Humans
Interleukin-6 / genetics
Interleukin-6 / metabolism
Membrane Proteins / agonists
Membrane Proteins / antagonists & inhibitors
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Molecular Sequence Annotation
Phosphatidylinositol 3-Kinases / genetics*
Phosphatidylinositol 3-Kinases / metabolism
Plasmids / chemistry
Plasmids / metabolism
Proto-Oncogene Proteins c-akt / genetics*
Proto-Oncogene Proteins c-akt / metabolism
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Signal Transduction / genetics*
Syk Kinase / genetics
Syk Kinase / metabolism
Transcriptome*
Transfection
Vascular Endothelial Growth Factor Receptor-1 / genetics
Vascular Endothelial Growth Factor Receptor-1 / metabolism
Vascular Endothelial Growth Factor Receptor-3 / genetics
Vascular Endothelial Growth Factor Receptor-3 / metabolism

Substances

CEMIP2 protein, human
IL6 protein, human
Interleukin-6
Membrane Proteins
RNA, Small Interfering
FLT1 protein, human
FLT4 protein, human
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-3
SYK protein, human
Syk Kinase
AKT3 protein, human
Proto-Oncogene Proteins c-akt