Hsa-let-7a functions as a tumor suppressor in renal cell carcinoma cell lines by targeting c-myc

Biochem Biophys Res Commun. 2012 Jan 6;417(1):371-5. doi: 10.1016/j.bbrc.2011.11.119. Epub 2011 Dec 1.

Abstract

Widespread functions of the c-myc pathway play a crucial role in renal cell carcinoma (RCC) carcinogenesis. Thus, we evaluated the connection between proto-oncogenic c-myc and anti-neoplastic hsa-let-7a (let-7a) in RCC cell lines. The levels of c-myc and let-7a in 3 RCC cell lines (769P, Caki-1 and 786O) were measured after transfecting the cells with let-7a mimics or a negative control. The change in c-myc protein level was confirmed by Western blot. The anti-neoplastic function of let-7a was evaluated using cell counting kit-8 (CCK-8) for proliferation analysis and cell flow cytometry for cell cycle analysis. The changes of downstream targets of c-myc were measured using reverse transcription quantitative real-time PCR (qRT-PCR). Our results suggest for the first time that let-7a acts as a tumor suppressor in RCC cell lines by down-regulating c-myc and c-myc target genes such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and the miR17-92 cluster, which is accompanied by proliferation inhibition and cell cycle arrest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cyclin D1 / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor / physiology*
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology*
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Proliferating Cell Nuclear Antigen / genetics
  • Proto-Oncogene Proteins c-myc / genetics*
  • RNA, Long Noncoding

Substances

  • MIR17HG, human
  • MYC protein, human
  • MicroRNAs
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • mirnlet7 microRNA, human
  • Cyclin D1