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Knockdown of TIGAR by RNA interference induces apoptosis and autophagy in HepG2 hepatocellular carcinoma cells.
Biochem Biophys Res Commun. 2013 Jul 26; 437(2):300-6.BB

Abstract

Apoptosis and autophagy are crucial mechanisms regulating cell death, and the relationship between apoptosis and autophagy in the liver has yet to be thoroughly explored. TIGAR (TP53-induced glycolysis and apoptosis regulator), which is a p53-inducible gene, functions in the suppression of ROS (reactive oxygen species) and protects U2OS cells from undergoing cell death. In this study, silencing TIGAR by RNAi (RNA interference) in HepG2 cells down-regulated both TIGAR mRNA (∼75%) and protein levels (∼80%) and led to the inhibition of cell growth (P<0.01) by apoptosis (P<0.001) and autophagy. We demonstrated that TIGAR can increase ROS levels in HepG2 cells. The down-regulation of TIGAR led to the induction of LC-3 II (specific autophagic marker), the formation of the autophagosome, and increased Beclin-1 expression. 3-MA (3-Methyladenine), an inhibitor of autophagic sequestration blocker, inhibited TIGAR siRNA-enhanced autophagy, as indicated by the decrease in LC-3 II levels. Consequently, these data provide the first evidence that targeted silencing of TIGAR induces apoptotic and autophagic cell death in HepG2 cells, and our data raise hope for the future successful application of TIGAR siRNA in patients with hepatocellular carcinoma (HCC).

Authors+Show Affiliations

Laboratory of Neuroimmunology and Regenerative Therapy, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5930, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23817040

Citation

Ye, Ling, et al. "Knockdown of TIGAR By RNA Interference Induces Apoptosis and Autophagy in HepG2 Hepatocellular Carcinoma Cells." Biochemical and Biophysical Research Communications, vol. 437, no. 2, 2013, pp. 300-6.
Ye L, Zhao X, Lu J, et al. Knockdown of TIGAR by RNA interference induces apoptosis and autophagy in HepG2 hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2013;437(2):300-6.
Ye, L., Zhao, X., Lu, J., Qian, G., Zheng, J. C., & Ge, S. (2013). Knockdown of TIGAR by RNA interference induces apoptosis and autophagy in HepG2 hepatocellular carcinoma cells. Biochemical and Biophysical Research Communications, 437(2), 300-6. https://doi.org/10.1016/j.bbrc.2013.06.072
Ye L, et al. Knockdown of TIGAR By RNA Interference Induces Apoptosis and Autophagy in HepG2 Hepatocellular Carcinoma Cells. Biochem Biophys Res Commun. 2013 Jul 26;437(2):300-6. PubMed PMID: 23817040.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Knockdown of TIGAR by RNA interference induces apoptosis and autophagy in HepG2 hepatocellular carcinoma cells. AU - Ye,Ling, AU - Zhao,Xiaoping, AU - Lu,Jian, AU - Qian,Guanxiang, AU - Zheng,Jialin C, AU - Ge,Shengfang, Y1 - 2013/06/28/ PY - 2013/06/14/received PY - 2013/06/20/accepted PY - 2013/7/3/entrez PY - 2013/7/3/pubmed PY - 2013/10/18/medline KW - Apoptosis KW - Autophagy KW - HCC KW - Hepatocellular carcinoma KW - RNA interference KW - RNAi KW - ROS KW - TIGAR KW - TP53-induced glycolysis and apoptosis regulator KW - hepatocellular carcinoma KW - reactive oxygen species KW - siRNA KW - siRNA for TIGAR KW - siTIGAR KW - small interference RNA SP - 300 EP - 6 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 437 IS - 2 N2 - Apoptosis and autophagy are crucial mechanisms regulating cell death, and the relationship between apoptosis and autophagy in the liver has yet to be thoroughly explored. TIGAR (TP53-induced glycolysis and apoptosis regulator), which is a p53-inducible gene, functions in the suppression of ROS (reactive oxygen species) and protects U2OS cells from undergoing cell death. In this study, silencing TIGAR by RNAi (RNA interference) in HepG2 cells down-regulated both TIGAR mRNA (∼75%) and protein levels (∼80%) and led to the inhibition of cell growth (P<0.01) by apoptosis (P<0.001) and autophagy. We demonstrated that TIGAR can increase ROS levels in HepG2 cells. The down-regulation of TIGAR led to the induction of LC-3 II (specific autophagic marker), the formation of the autophagosome, and increased Beclin-1 expression. 3-MA (3-Methyladenine), an inhibitor of autophagic sequestration blocker, inhibited TIGAR siRNA-enhanced autophagy, as indicated by the decrease in LC-3 II levels. Consequently, these data provide the first evidence that targeted silencing of TIGAR induces apoptotic and autophagic cell death in HepG2 cells, and our data raise hope for the future successful application of TIGAR siRNA in patients with hepatocellular carcinoma (HCC). SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/23817040/Knockdown_of_TIGAR_by_RNA_interference_induces_apoptosis_and_autophagy_in_HepG2_hepatocellular_carcinoma_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(13)01070-X DB - PRIME DP - Unbound Medicine ER -