Overexpression of miR-215-3p sensitizes colorectal cancer to 5-fluorouracil induced apoptosis through regulating CXCR1

Eur Rev Med Pharmacol Sci. 2018 Nov;22(21):7240-7250. doi: 10.26355/eurrev_201811_16258.

Abstract

Objective: Chemo-resistance of colon cancer remains a major problem in therapy. The role of miR-215-3p in the chemo-sensitivity of colon cancer remains unidentified.

Patients and methods: Here, we constructed a 5-Fluoracil (5-Fu) resistant HCT116 cell line (HCT116/5-Fu) and miR-215-3p expression levels were measured in 56 cases of colon cancer tissues and 23 cases of normal tissues by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of miR-215-3p on colon cancer cell growth and apoptosis were investigated using cell counting kit-8 (CCK-8) and apoptosis assay, respectively. In addition, CXC-chemokine receptor type1 (CXCR1) was identified as a target of miR-215-3p by using luciferase reporter assay.

Results: miR-215-3p was down-expressed in the 5-FU resistant cell compared to the parent cell. The level of miR-215-3p was correlated with the 5-Fu sensibility of colorectal cancer cell and the alteration of miR-215-3p affected the sensibility of colorectal cancer cells toward 5-Fu. Furthermore, miR-215-3p accelerated the apoptosis of colorectal cancer cell which was treated with 5-Fu. Mechanically, miR-215-3p regulated the level of endogenous CXCR1 in HCT116 cell and alternation of CXCR1 affected the 5-Fu sensibility mediated by miR-215-3p. Finally, overexpression of miR-215-3p restrained the growth of HCT116/5-Fu cells in the xenograft model.

Conclusions: MiR-215-3p improved the 5-Fu sensibility via regulating the expression of CXCR1 in the colorectal cancer cell.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / pharmacology*
  • Apoptosis / drug effects*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm
  • Female
  • Fluorouracil / pharmacology*
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Receptors, Interleukin-8A / genetics
  • Receptors, Interleukin-8A / metabolism*
  • Signal Transduction
  • Tumor Burden / drug effects
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • Antimetabolites, Antineoplastic
  • MIRN215 microRNA, human
  • MicroRNAs
  • Receptors, Interleukin-8A
  • Fluorouracil