Transcriptome alteration upon ZNF281 depletion in HCC cells

ABSTRACT: To find potential target gene of ZNF281 in HCC cells, the transcriptome analyse (RNA-seq) were performed in HLE HCC cell lines with or with ZNF281 depletion using shRNAs in lentivirus vectors Zinc finger protein 281 (ZNF281) has been implicated in the progression of several types of cancer. However, its functionality and transcriptional targets in hepatocellular carcinoma (HCC) remains elusive. In the present study, we discovered that the expression of ZNF281 was increased in tumor tissues and cell lines, and positively correlated with vessel invasion in HCC. We took RNA interference approach and constructed 2 shRNAs lentivirus vectors targeting different regions of ZNF281 which were named as ZNF281.kd1 and ZNF281.kd2 respectively. Knockdown of ZNF281 suppressed proliferation, migration and invasion of HCC cells. In searching for novel ZNF281 regulated genes, RNA-seq was performed on BGI-seq500 platform using the obtained stable cells of Con, ZNF281.kd1 and ZNF281.kd2 in HLE background (each in duplicate). The criteria of log2 FC (fold change) >1.5, and q value <0.001 was set for calling differentially expressed genes (DEGs). Besides, to minimize the off-target effect of single shRNAs, only DEGs that show consistent trend of alteration (up-regulated or down-regulated in both ZNF281.kd1 and ZNF281.kd2 groups against control shRNA group) were selected as potential ZNF281 targets. A list of potential targets was identified, including both up-regulated and down-regulated genes upon ZNF281 depletion. Further mechanistic studies were performed to uncover transcriptional regulation of ZNF281 on these genes. Our study was supposed to be helpful for understanding the molecular mechanism underpinning progression of HCC, and might also hold therapeutic potential for HCC treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE146496 | GEO | 2020/03/07

REPOSITORIES: GEO