Overexpression of MEG3 sensitizes colorectal cancer cells to oxaliplatin through regulation of miR-141/PDCD4 axis

Biomed Pharmacother. 2018 Oct:106:1607-1615. doi: 10.1016/j.biopha.2018.07.131. Epub 2018 Jul 29.

Abstract

The existence of drug resistance is the main reason for chemotherapeutic failure in malignancies. Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) is implicated with tumorigenesis and chemoresistance. In the present study, we aimed to identify the role of MEG3 in oxaliplatin-resistant colorectal cancer (CRC) and its potential mechanisms. MEG3 was down-regulated in oxaliplatin-resistant CRC tissues and cell lines. Low MEG3 expression was correlated with poor prognosis of CRC patients. Overexpression of MEG3 improved oxaliplatin sensitivity of HT29/OXA and HCT116/OXA cells. MEG3 suppressed miR-141 expression in HCT116/OXA cells. Moreover, MEG3 elevated PDCD4 expression through targeting miR-141, acting as a competing endogenous RNA (ceRNA). miR-141 inhibition or PDCD4 up-regulation could mimic the functional role in oxaliplatin resistance, which was counteracted by overexpression of MEG3. Collectively, MEG3 facilitated the sensitivity of CRC cells to oxaliplatin by regulating miR-141/PDCD4 axis, providing a novel therapeutic strategy for CRC.

Keywords: Colorectal cancer; Oxaliplatin; PDCD4; lncRNA MEG3; miR-141.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Oxaliplatin / pharmacology*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction / drug effects
  • Time Factors
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • MEG3 non-coding RNA, human
  • MIRN141 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • Oxaliplatin