Long noncoding RNA FOXD3-AS1 promotes colon adenocarcinoma progression and functions as a competing endogenous RNA to regulate SIRT1 by sponging miR-135a-5p

J Cell Physiol. 2019 Dec;234(12):21889-21902. doi: 10.1002/jcp.28752. Epub 2019 May 6.

Abstract

More and more documents have proved that the abnormal expression of long noncoding RNAs (lncRNAs) are correlated with the initiation and progression of colorectal cancer (CRC). lncRNA FOXD3-AS1 has been reported in glioma for its oncogenic property. According to the survival analysis of The Cancer Genome Atlas database, FOXD3-AS1 upregulation implied lower survival rate of patients with CRC. Quantitative real-time polymerase chain reaction showed the overexpression of FOXD3-AS1 in both CRC tissues and cells. The Kaplan-Meier method demonstrated the prognostic value of FOXD3-AS1 for patients with CRC. To explore the effect of FOXD3-AS1 on CRC progression, loss-of-function experiments were carried out, whose results indicated that knockdown of FOXD3-AS1 suppressed cell proliferation, migration, and invasion, inhibited cell cycle and promoted cell apoptosis in vitro. In vivo experiments affirmed that FOXD3-AS1 affected tumor growth. FOXD3-AS1 expression was enriched in the cytoplasm of CRC cells. Mechanism experiments revealed that FOXD3-AS1 served as a competing endogenous RNA to upregulate SIRT1 by sponging miR-135a-5p. In addition, SIRT1 silencing also restrained cell proliferation and motility. Rescue assays revealed the biological function of FOXD3-AS1/miR-135a-5p/SIRT1 axis in CRC progression. In conclusion, FOXD3-AS1 promotes CRC progression by regulating miR-135a-5p/SIRT1 axis, shedding lights on the way to CRC treatments.

Keywords: SIRT1; colorectal cancer; lncRNA FOXD3-AS1; miR-135a-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics*
  • Apoptosis / genetics
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic / genetics*
  • Glioma / pathology
  • Humans
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Sirtuin 1 / genetics*

Substances

  • FOXD3 protein, human
  • Forkhead Transcription Factors
  • MIRN135 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SIRT1 protein, human
  • Sirtuin 1