Over-expression of telomere binding factors (TRF1 & TRF2) in renal cell carcinoma and their inhibition by using SiRNA induce apoptosis, reduce cell proliferation and migration invitro

PLoS One. 2015 Mar 2;10(3):e0115651. doi: 10.1371/journal.pone.0115651. eCollection 2015.

Abstract

Telomere binding factors viz. TRF1 and TRF2 are a part of sheltrin complex that are present exclusively at the ends of chromosomes. These factors play an important role in maintaining chromosomal integrity at the ends. However, their status and role are not clear in renal cell carcinoma (RCC). Therefore, the present study was conducted to evaluate TRF1 and TRF2 expressions in RCC tissues. Further, the role of these factors involved in tumorigenesis was elucidated by gene silencing using siRNA in RCC cell line (A498). The present study documented a significant over-expression of TRF1 (P = 0.005) and TRF2 (P = 0.0048) mRNAs by real time PCR in RCC tissues as compared with adjacent normal kidney tissues. Immunohistochemistry studies also revealed higher expression of TRF1 and TRF2 proteins in RCC. Moreover, TRF1 or TRF2 gene silencing using siRNA showed marked reduction in proliferation of RCC cells (P = 0.000). Further, significantly induced cell cycle arrest (P = 0.000) and apoptosis of RCC cells (P = 0.000) was documented upon TRF1 or TRF2 gene silencing. Henceforth, the results deduce that TRF1 or TRF2 inhibitions play an important role in the induction of apoptosis in A498 cells, which may serve as a potential therapeutic target in RCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • Humans
  • Immunohistochemistry
  • Kidney / metabolism
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Male
  • Middle Aged
  • RNA, Small Interfering / metabolism*
  • S Phase Cell Cycle Checkpoints
  • Telomeric Repeat Binding Protein 1 / antagonists & inhibitors
  • Telomeric Repeat Binding Protein 1 / genetics
  • Telomeric Repeat Binding Protein 1 / metabolism*
  • Telomeric Repeat Binding Protein 2 / antagonists & inhibitors
  • Telomeric Repeat Binding Protein 2 / genetics
  • Telomeric Repeat Binding Protein 2 / metabolism*
  • Up-Regulation

Substances

  • RNA, Small Interfering
  • Telomeric Repeat Binding Protein 1
  • Telomeric Repeat Binding Protein 2

Grant support

This is a part of a research project funded by Council of Scientific and Industrial Research, New Delhi, India (vide letter no. 27/0218/09/EMR-II). The authors are thankful to Indian council of medical research, New Delhi, India for awarding junior and senior research fellowship (3/1/3/JRF-2010/HRD-67(11065). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.