Gene associated with retinoid-interferon-induced mortality-19 suppresses growth of lung adenocarcinoma tumor in vitro and in vivo.
Lung cancer is currently the leading cause of cancer-related death in the world. Signal transducers and activators of transcription 3 (STAT3) is a major oncogenic transcription factor involved in the development and progression of a number of human tumors including lung denocarcinoma. Gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) is known to functionally interact with STAT3 and inhibit its transcriptional activity. Decreased expression of GRIM-19 has been reported in tumors including those from kidney, prostate, colon and cervix, indicating that loss of GRIM-19 may be involved in the tumorigenesis through activation of the STAT3 pathway. In this study, we determined that GRIM-19 was significantly reduced at the mRNA and protein levels in lung adenocarcinoma tissues. Moreover, STAT3 was increased in these tumors and corresponding changes in the expression of its downstream target genes was observed. Overexpression of GRIM-19 was also found to suppress lung adenocancinoma tumor growth both in vitro and in vivo. Taken together, these findings will likely contribute to the future development of GRIM-19-based gene therapy approaches to treat lung adenocancinoma.
Department of Pulmonary, Anhui Geriatric Institute, First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei 230022, Anhui, China.
Tong
T
Wang
Xue-Bo
XB
Yan
Ji-Jing
JJ
Zhao
Jing
J
Ye
Zi-Feng
ZF
Jiang
Dao-Rong
DR
Wu
Wei-Hua
WH
Xiao
Rong-Yu
RY
Liu
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D047368:Tumor Burden / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D051017:Apoptosis Regulatory Proteins; D006131:Growth Inhibitors; D050796:STAT3 Transcription Factor; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human