Biostatistics mining associated method identifies AKR1B10 enhancing hepatocellular carcinoma cell growth and degenerated by miR-383-5p

Junqing Wang, Yunyun Zhou, Xiaochun Fei, Xuehua Chen, Yongjun Chen

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Previous studies have reported that the aberrantly expressed AKR1B10 is associated with many cancer development, however the functional roles of AKR1B10 and its regulatory mechanisms in hepatocellular carcinoma (HCC) have been limited studied. In this project, we identified AKR1B10 functional as an oncogene in HCC through tumor/normal human tissue comparison from both GEO microarray and TCGA RNAseq dataset. Further experimental validations from three HCC cell lines (SMMC-7721, HePG2 and HeP3B) also suggested the ontogenetic functions of AKR1B10 in HCC tumor growth. By knocking down AKR1B10 through shRNA in HCC HeP3B cells, we showed it significantly induced cell cycle arrest and inhibited cell growth. Interestingly, integrative analysis of TCGA RNAseq data and miRNA-seq data predicted that miR-383-5p, a novel post-transcriptional tumor suppressor, is negatively associated with AKR1B10 expression. To further investigate the role of miR-383-5p in regulating AKR1B10 in HCC, we performed Dual-luciferase reporter assay experiments. Results showed that miR-383-5p is an upstream modulator targeting AKR1B10 in the post-transcriptional stage. Thus, we report AKR1B10 modulated regulated by miR-383-5p, promotes HCC tumor progress, and could be potentially a therapeutic target for precision medicine in HCC.

Original languageEnglish
Article number11094
Pages (from-to)11094
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Jun 23 2018

Keywords

  • Aldehyde Reductase/metabolism
  • Aldo-Keto Reductases
  • Biostatistics
  • Carcinoma, Hepatocellular/genetics
  • Cell Cycle Checkpoints/genetics
  • Cell Line, Tumor
  • Cell Proliferation/genetics
  • Data Mining
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Liver Neoplasms/genetics
  • MicroRNAs/genetics
  • Protein Interaction Mapping
  • RNA, Messenger/genetics
  • Transcription, Genetic

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