Long non-coding RNA HNF1A-AS1 mediated repression of miR-34a/SIRT1/p53 feedback loop promotes the metastatic progression of colon cancer by functioning as a competing endogenous RNA

Cancer Lett. 2017 Dec 1;410:50-62. doi: 10.1016/j.canlet.2017.09.012. Epub 2017 Sep 21.

Abstract

In recent years, accumulating evidence indicates that long noncoding RNAs (lncRNAs) have emerged as powerful influence factors in the progression of multiple malignancies. Dysregulation of lncRNA HNF1A-antisense 1 (HNF1A-AS1) has been reported in many types of human cancers, and studies on HNF1A-AS1 function in cancers revealed that HNF1A-AS1could act as either oncogene or tumor suppressor. Nevertheless, the functional involvement of HNF1A-AS1 in colon cancer remains unknown. In this study, we reported that HNF1A-AS1 was frequently upregulated in colon cancer tissues and associated with poor prognosis. Upregulated HNF1A-AS1 promoted colon cancer cell viability, migration and invasion both in vitro and in vivo. HNF1A-AS1 silencing impaired tumor growth and metastasis in xenograft model assay. Moreover, HNF1A-AS1 functioned as an oncogene in metastasis of colon cancer in part through serving as a competing endogenous RNA to modulate miRNA-34a expression, subsequently with repression of miR-34a/SIRT1/p53 feedback loop and activation of canonical Wnt signaling pathway. Our results demonstrated that HNF1A-AS1 mediated the metastatic progression of colon cancer in part through miR-34a/p53 signaling axis, and established its candidacy as a new prognostic biomarker and a potential novel therapeutic target.

Keywords: HNF1A-AS1; Metastasis; ceRNA; miRNA-34a; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Binding, Competitive
  • Caco-2 Cells
  • Cell Movement*
  • Cell Proliferation
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Feedback, Physiological
  • Female
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Metastasis
  • Phenotype
  • Protein Binding
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Signal Transduction
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism
  • Time Factors
  • Tumor Burden
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation

Substances

  • MIRN34 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • long non-coding RNA HNF1A-AS1, human
  • SIRT1 protein, human
  • Sirtuin 1