Double stranded-RNA-mediated activation of P21 gene induced apoptosis and cell cycle arrest in renal cell carcinoma

Jared M Whitson, Emily J. Noonan, Deepa Pookot, Robert F. Place, Rajvir Dahiya

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Small double stranded RNAs (dsRNA) are a new class of molecules which regulate gene expression. Accumulating data suggest that some dsRNA can function as tumor suppressors. Here, we report further evidence on the potential of dsRNA mediated p21 induction. Using the human renal cell carcinoma cell line A498, we found that dsRNA targeting the p21 promoter significantly induced the expression of p21 mRNA and protein levels. As a result, dsP21 transfected cells had a significant decrease in cell viability with a concomitant G1 arrest. We also observed a significant increase in apoptosis. These findings were associated with a significant decrease in survivin mRNA and protein levels. This is the first report that demonstrates dsRNA mediated gene activation in renal cell carcinoma and suggests that forced over-expression of p21 may lead to an increase in apoptosis through a survivin dependent mechanism.

Original languageEnglish (US)
Pages (from-to)446-452
Number of pages7
JournalInternational Journal of Cancer
Volume125
Issue number2
DOIs
StatePublished - Jul 15 2009
Externally publishedYes

Fingerprint

Double-Stranded RNA
Cell Cycle Checkpoints
Renal Cell Carcinoma
Transcriptional Activation
Apoptosis
Messenger RNA
Cell Survival
Proteins
Gene Expression
Cell Line
Neoplasms

Keywords

  • Apoptosis
  • p21WAF1/CIP1
  • Renal cell carcinoma
  • RNAa
  • saRNA
  • Survivin/Birc5

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Double stranded-RNA-mediated activation of P21 gene induced apoptosis and cell cycle arrest in renal cell carcinoma. / Whitson, Jared M; Noonan, Emily J.; Pookot, Deepa; Place, Robert F.; Dahiya, Rajvir.

In: International Journal of Cancer, Vol. 125, No. 2, 15.07.2009, p. 446-452.

Research output: Contribution to journalArticle

Whitson, Jared M ; Noonan, Emily J. ; Pookot, Deepa ; Place, Robert F. ; Dahiya, Rajvir. / Double stranded-RNA-mediated activation of P21 gene induced apoptosis and cell cycle arrest in renal cell carcinoma. In: International Journal of Cancer. 2009 ; Vol. 125, No. 2. pp. 446-452.
@article{849127ec608b4f31be05736e3a375cc0,
title = "Double stranded-RNA-mediated activation of P21 gene induced apoptosis and cell cycle arrest in renal cell carcinoma",
abstract = "Small double stranded RNAs (dsRNA) are a new class of molecules which regulate gene expression. Accumulating data suggest that some dsRNA can function as tumor suppressors. Here, we report further evidence on the potential of dsRNA mediated p21 induction. Using the human renal cell carcinoma cell line A498, we found that dsRNA targeting the p21 promoter significantly induced the expression of p21 mRNA and protein levels. As a result, dsP21 transfected cells had a significant decrease in cell viability with a concomitant G1 arrest. We also observed a significant increase in apoptosis. These findings were associated with a significant decrease in survivin mRNA and protein levels. This is the first report that demonstrates dsRNA mediated gene activation in renal cell carcinoma and suggests that forced over-expression of p21 may lead to an increase in apoptosis through a survivin dependent mechanism.",
keywords = "Apoptosis, p21WAF1/CIP1, Renal cell carcinoma, RNAa, saRNA, Survivin/Birc5",
author = "Whitson, {Jared M} and Noonan, {Emily J.} and Deepa Pookot and Place, {Robert F.} and Rajvir Dahiya",
year = "2009",
month = "7",
day = "15",
doi = "10.1002/ijc.24370",
language = "English (US)",
volume = "125",
pages = "446--452",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Double stranded-RNA-mediated activation of P21 gene induced apoptosis and cell cycle arrest in renal cell carcinoma

AU - Whitson, Jared M

AU - Noonan, Emily J.

AU - Pookot, Deepa

AU - Place, Robert F.

AU - Dahiya, Rajvir

PY - 2009/7/15

Y1 - 2009/7/15

N2 - Small double stranded RNAs (dsRNA) are a new class of molecules which regulate gene expression. Accumulating data suggest that some dsRNA can function as tumor suppressors. Here, we report further evidence on the potential of dsRNA mediated p21 induction. Using the human renal cell carcinoma cell line A498, we found that dsRNA targeting the p21 promoter significantly induced the expression of p21 mRNA and protein levels. As a result, dsP21 transfected cells had a significant decrease in cell viability with a concomitant G1 arrest. We also observed a significant increase in apoptosis. These findings were associated with a significant decrease in survivin mRNA and protein levels. This is the first report that demonstrates dsRNA mediated gene activation in renal cell carcinoma and suggests that forced over-expression of p21 may lead to an increase in apoptosis through a survivin dependent mechanism.

AB - Small double stranded RNAs (dsRNA) are a new class of molecules which regulate gene expression. Accumulating data suggest that some dsRNA can function as tumor suppressors. Here, we report further evidence on the potential of dsRNA mediated p21 induction. Using the human renal cell carcinoma cell line A498, we found that dsRNA targeting the p21 promoter significantly induced the expression of p21 mRNA and protein levels. As a result, dsP21 transfected cells had a significant decrease in cell viability with a concomitant G1 arrest. We also observed a significant increase in apoptosis. These findings were associated with a significant decrease in survivin mRNA and protein levels. This is the first report that demonstrates dsRNA mediated gene activation in renal cell carcinoma and suggests that forced over-expression of p21 may lead to an increase in apoptosis through a survivin dependent mechanism.

KW - Apoptosis

KW - p21WAF1/CIP1

KW - Renal cell carcinoma

KW - RNAa

KW - saRNA

KW - Survivin/Birc5

UR - http://www.scopus.com/inward/record.url?scp=67449097427&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67449097427&partnerID=8YFLogxK

U2 - 10.1002/ijc.24370

DO - 10.1002/ijc.24370

M3 - Article

C2 - 19384944

AN - SCOPUS:67449097427

VL - 125

SP - 446

EP - 452

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 2

ER -