Lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-Ras

Int J Radiat Oncol Biol Phys. 2010 Jan 1;76(1):5-8. doi: 10.1016/j.ijrobp.2009.08.028.

Abstract

Purpose: To evaluate the potential of targeting Lin28-let7 microRNA regulatory network for overcoming the radioresistance of cancer cells having activated K-Ras signaling.

Methods and materials: A549 lung carcinoma cells and ASPC1 pancreatic cancer cells possessing K-RAS mutation were transfected with pre-let7a microRNA or Lin28 siRNA, respectively. Clonogenic assay, quantitative reverse transcription polymerase chain reaction, and Western analysis were performed. The effects of Lin28 on SQ20B cells having wild-type K-RAS, and a normal fibroblast were also assessed.

Results: The overexpression of let-7a decreased expression of K-Ras and radiosensitized A549 cells. Inhibition of Lin28, a repressor of let-7, attenuated K-Ras expression and radiosensitized A549 and ASPC1 cells. Neither SQ20B cells expressing wild-type K-RAS nor HDF, the normal human fibroblasts, were radiosensitized by this approach.

Conclusions: The Lin28-let7 regulatory network may be a potentially useful therapeutic target for overcoming the radioresistance of human cancers having activated K-Ras signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor / radiation effects
  • Fibroblasts / radiation effects
  • Gene Expression
  • Genes, ras / genetics*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / radiotherapy
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mutation / genetics
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / radiotherapy
  • RNA, Small Interfering / genetics*
  • RNA-Binding Proteins / antagonists & inhibitors*
  • RNA-Binding Proteins / genetics
  • Radiation Tolerance / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Signal Transduction / radiation effects
  • Transfection / methods
  • Tumor Stem Cell Assay
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • LIN-28 protein, human
  • MicroRNAs
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • mirnlet7 microRNA, human
  • ras Proteins