Lin28A enhances chemosensitivity of colon cancer cells to 5-FU by promoting apoptosis in a let-7 independent manner

Tumour Biol. 2016 Jun;37(6):7657-65. doi: 10.1007/s13277-015-4559-8. Epub 2015 Dec 21.

Abstract

RNA-binding protein Lin28A is frequently over-expressed in human malignant tumors and is associated with tumor advance and poor prognosis. However, the expression pattern and functions of Lin28A in colon cancer are unknown. In this study, we detected the expression of Lin28A in colon cancer patients and tested the effect of Lin28A on the chemotherapeutic sensitivity of colon cancer cells to 5-fluorouracil (5-FU). As expected, we showed that Lin28A is up-regulated in 73.3 % of colon cancer patients. However, to our surprise, we found that oncogenic protein Lin28A-enforced expression in colon cancer cells enhanced the chemosensitivity of cancer cells to 5-FU via promoting the cell apoptosis. Further mechanisms study revealed that the effect of Lin28A increasing chemosensitivity of cancer cells is in a let-7 independent manner, but which is associated with decreasing the expression of DNA damage repair protein H2AX. Conclusively, here we reported an unexpected function of Lin28A, which may shed lights on fully understanding the physiological and pathological roles of this oncogene.

Keywords: Apoptosis; Chemosensitivity; Colon cancer; H2AX; Lin28A.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • DNA Repair / drug effects
  • Drug Resistance, Neoplasm
  • Female
  • Fluorouracil / pharmacology*
  • HCT116 Cells
  • Histones / biosynthesis
  • Histones / genetics
  • Humans
  • Male
  • MicroRNAs / physiology
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • RNA, Neoplasm / physiology
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / physiology*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Single-Blind Method

Substances

  • Antimetabolites, Antineoplastic
  • H2AX protein, human
  • Histones
  • LIN28B protein, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • mirnlet7 microRNA, human
  • Fluorouracil