Stat3 inhibits Beclin 1 expression through recruitment of HDAC3 in nonsmall cell lung cancer cells.
Recent studies have shown that Beclin 1, a key regulator of autophagic process, is frequently downregulated and may serve as an independent prognostic biomarker for nonsmall cell lung cancer. However, the molecular mechanisms underlying its downregulation remain poorly understood. The signal transducer and activator of transcription 3 (Stat3) is a transcription factor which plays a crucial role for multiple tumor growth and progression. Here, we demonstrate that Beclin 1 is a direct transcriptional target of Stat3 in lung cancer cells. Interleukin-6 (IL-6) treatment or transfection of a constitutively activated Stat3 in AGS and NCI-H1650 cells inhibited Beclin 1 expression. At the molecular level, we further revealed that Stat3 could directly bind to the promoter region of Beclin 1 and repressed its transcription through recruiting histone deacetylase 3 (HDAC3). Collectively, our results suggest that the activated Stat3 may represent an important mechanism for Beclin 1 downregulation in nonsmall cell lung cancer development.
Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Li-Jun
LJ
Miao
Feng-Xiang
FX
Huang
Zhen-Tao
ZT
Sun
Rui-Xia
RX
Zhang
Shi-Fu
SF
Huang
Jing
J
Wang
D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D000071186:Beclin-1; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000008:administration & dosage / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000099186:Histone Deacetylase 3
D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D006655:Histone Deacetylases; D015850:Interleukin-6; D008565:Membrane Proteins; D050796:STAT3 Transcription Factor; D000099186:Histone Deacetylase 3; C491997:BECN1 protein, human; C494086:STAT3 protein, human