RNAa-mediated overexpression of WT1 induces apoptosis in HepG2 cells

© 2012 Qin et al; licensee BioMed Central Ltd..

AIM: Recent studies have reported that double-stranded RNA (dsRNA) can activate gene expression by targeting promoter sequence in a process termed RNA activation. The present study was conducted to evaluate the potential of WT1 induction by small activating RNA targeting the WT1 promoter (dsWT1) in the treatment of hepatocellular carcinoma.

METHODS: The human hepatocellular carcinoma cell line HepG2 was transfected with dsRNA by liposomes. The expression of mRNA and protein in cells were investigated using real-time reverse real-time quantitative PCR and Western blot, respectively. Cell viability and clonogenicity were determined by MTT assay and clonogenicity assay, respectively. Cell apoptosis was evaluated by flow-cytometric analysis.

RESULTS: Expressions of WT1 mRNA and protein in dsWT1 treated HepG2 cells were significantly elevated. Inhibition of cell viability by dsWT1 was dose-dependent and time-dependent. Reduction of the number and size of colonies formed were found in dsWT1 treated cells. dsWT1 induced significant apoptosis in HepG2 cells. The decreased anti-apoptotic protein Bcl-2 and elevated pro-apoptotic protein Bak expression were detected in dsWT1 treated cells. The level of pro-caspase-3 remarkably decreased and cleaved caspase-3 and PARP fragment were also detected in dsWT1 treated cells.

CONCLUSION: These data show that RNAa-mediated overexpression of WT1 may have therapeutic potential in the treatment of hepatocellular carcinoma.

Medienart:

E-Artikel

Erscheinungsjahr:

2012

Erschienen:

2012

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

World journal of surgical oncology - 10(2012) vom: 13. Jan., Seite 11

Sprache:

Englisch

Beteiligte Personen:

Qin, Qi [VerfasserIn]
Lin, Yi-Wei [VerfasserIn]
Zheng, Xiang-Yi [VerfasserIn]
Chen, Hong [VerfasserIn]
Mao, Qi-Qi [VerfasserIn]
Yang, Kai [VerfasserIn]
Huang, Shou-Jiang [VerfasserIn]
Zhao, Zheng-Yan [VerfasserIn]

Links:

Volltext

Themen:

BAX protein, human
Bcl-2-Associated X Protein
Caspase 3
EC 3.4.22.-
Journal Article
Proto-Oncogene Proteins c-bcl-2
RNA, Double-Stranded
RNA, Messenger
Research Support, Non-U.S. Gov't
WT1 Proteins

Anmerkungen:

Date Completed 01.06.2012

Date Revised 21.10.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1186/1477-7819-10-11

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM21454656X