Long non-coding SBF2-AS1 acting as a competing endogenous RNA to sponge microRNA-142-3p to participate in gemcitabine resistance in pancreatic cancer via upregulating TWF1

Aging (Albany NY). 2019 Nov 4;11(20):8860-8878. doi: 10.18632/aging.102307.

Abstract

Objective: This study is implemented to probe into the function of lncRNA SBF2-AS1 as a competing endogenous RNA (ceRNA) to sponge microRNA-142-3p (miR-142-3p) in modulating TWF1 expression in the gemcitabine resistance of pancreatic cancer.

Results: LncRNA SBF2-AS1 was highly expressed in pancreatic cancer tissues and cells. SBF2-AS1 was found to be associated with gemcitabine resistance in pancreatic cancer. Knock-down of SBF2-AS1 inhibited proliferation, epithelial-mesenchymal transition, while promoting apoptosis of gemcitabine resistant pancreatic cancer cells. SBF2-AS1 inhibited the expression of TWF1 by competitively binding with miR-142-3p in pancreatic cancer.

Conclusion: Our study demonstrates that knock-down of SBF2-AS1 inhibits the expression of TWF1 by competitively binding with miR-142-3p to induce gemcitabine resistance in pancreatic cancer.

Methods: Expression of SBF2-AS1 was tested in pancreatic cancer tissues and cells. Construction of AsPC-1/GEM and PANC-1/GEM cells with low expression of SBF2-AS1 was performed to determine the biological behaviors of drug-resistant cells. AsPC-1 and PANC-1 cells expressing SBF2-AS1 and/or miR-142-3p were constructed and treated with different concentrations of gemcitabine to detect the sensitivity of the cells to gemcitabine. The binding relationship between SBF2-AS1 and miR-142-3p and between miR-142-3p and TWF1 were determined.

Keywords: competing endogenous RNA; gemcitabine resistance; long non-coding SBF2-AS1; microRNA-142-3p; pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Drug Resistance, Neoplasm*
  • Female
  • Gemcitabine
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • MIRN142 microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • RNA, Long Noncoding
  • TWF1 protein, human
  • long non-coding RNA SBF2-AS1, human
  • Deoxycytidine
  • Protein-Tyrosine Kinases
  • Gemcitabine