miR-519b-3p promotes responsiveness to preoperative chemoradiotherapy in rectal cancer patients by targeting ARID4B

Gene. 2018 May 20:655:84-90. doi: 10.1016/j.gene.2018.02.056. Epub 2018 Mar 22.

Abstract

Recent evidences demonstrate that preoperative chemoradiotherapy (pCRT) followed by mesorectal excision is an effective therapy for patients with locally advanced rectal cancer (LARC). Nevertheless, the predictive molecular biomarkers for the response of patients to CRT remain largely unknown. Here we showed that the expression of miR-519b-3p was correlated with the responsiveness to pCRT in patients with LARC. We found that miR-519b-3p was highly expressed in responsive LARC samples. And we showed that miR-519b-3p may serve as a novel predictive marker by ROC analysis. In addition, overexpression of miR-519b-3p enhanced responsiveness to chemoradiation in vitro. Mechanistically, we found that miR-519b-3p directly bond to the 3' UTR of ARID4B mRNA whose expression was inversely correlated with miR-519b-3p expression. Finally, we performed functional experiments and showed that miR-519b-3p was directly involved in response to pCRT in rectal cancer patients in an ARID4B-dependent way.

Keywords: ARID4B; LARC; miR-519b-3p; pCRT.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Animals
  • Antigens, Neoplasm / genetics*
  • Cell Line, Tumor
  • Chemoradiotherapy, Adjuvant* / methods
  • Combined Modality Therapy
  • Digestive System Surgical Procedures*
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / physiology*
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics*
  • Preoperative Period
  • RNA Interference
  • Rectal Neoplasms / genetics
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / surgery
  • Rectal Neoplasms / therapy*
  • Xenograft Model Antitumor Assays

Substances

  • ARID4B protein, human
  • Antigens, Neoplasm
  • MIRN519 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins