Long non-coding RNA LINC01207 silencing suppresses AGR2 expression to facilitate autophagy and apoptosis of pancreatic cancer cells by sponging miR-143-5p

Mol Cell Endocrinol. 2019 Aug 1;493:110424. doi: 10.1016/j.mce.2019.04.004. Epub 2019 Apr 13.

Abstract

Pancreatic cancer is a serious malignancy accompanied by a well-documented poor prognosis. Accumulating studies have indicated the crucial roles played by long non-coding RNAs (lncRNAs) in proliferation, apoptosis and invasion of cancer cells. The aim of the current study was to investigate the role of lncRNA LINC01207 in autophagy and apoptosis of pancreatic cancer cells and its regulatory mechanism interacting with miR-143-5p. Initially, expression profiles of lncRNAs and genes associated with pancreatic cancer were identified. The expression patterns of LINC01207, miR-143-5p and AGR2 in both pancreatic cancer and adjacent tissues were then determined. The binding relationship of LINC01207 to miR-143-5p and targeting relationship of miR-143-5p to AGR2 were subsequently verified. Silencing of LINC01207, or up-regulation or down-regulation of miR-143-5p was introduced into the pancreatic cancer cells, so as to analyze their effects on the cell growth, apoptosis and autophagy. Besides, these regulatory effects were further explored with the determination of the autophagy- and apoptosis-related gene or proteins. LINC01207 and AGR2 were highly expressed while miR-143-5p was poorly expressed in pancreatic cancer. Functionally, LINC01207 can bind to miR-143-5p, and AGR2 was a target gene of miR-143-5p. Importantly, silencing of LINC01207 down-regulated the expression of AGR2 by up-regulating miR-143-5p. Moreover, silencing of LINC01207 and up-regulation of miR-143-5p promoted cell apoptosis and autophagy, corresponding to increased expression of autophagy- and apoptosis-related proteins, in addition to inhibited cell growth. Taken together, silencing of LINC01207 prevents the progression of pancreatic cancer by impairing miR-143-5p-targeted AGR2 expression, providing a potential target for pancreatic cancer treatment.

Keywords: AGR2; Apoptosis; Autophagy; Long non-coding RNA LINC01207; MicroRNA-143-5p; Pancreatic cancer.

MeSH terms

  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Autophagy
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Mucoproteins / genetics*
  • Mucoproteins / metabolism
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • RNA, Long Noncoding / genetics*

Substances

  • AGR2 protein, human
  • Apoptosis Regulatory Proteins
  • MIRN143 microRNA, human
  • MicroRNAs
  • Mucoproteins
  • Oncogene Proteins
  • RNA, Long Noncoding