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 transdu...

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Bibliographic Details
Published in:Tumor biology 2014-07, Vol.35 (7), p.7097-7103
Main Authors: Miao, Li-Jun, Huang, Feng-Xiang, Sun, Zhen-Tao, Zhang, Rui-Xia, Huang, Shi-Fu, Wang, Jing
Format: Article
Language:English
Subjects:
Apoptosis Regulatory Proteins - biosynthesis
Apoptosis Regulatory Proteins - genetics
Autophagy
Beclin-1
Biomarkers
Biomedical and Life Sciences
Biomedicine
Cancer Research
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Cell Line, Tumor
Gene expression
Gene Expression Regulation, Neoplastic
Histone Deacetylases - genetics
Histone Deacetylases - metabolism
Humans
Interleukin-6 - administration & dosage
Interleukin-6 - genetics
Lung cancer
Medical prognosis
Membrane Proteins - biosynthesis
Membrane Proteins - genetics
Promoter Regions, Genetic
Research Article
Signal Transduction
STAT3 Transcription Factor - genetics
STAT3 Transcription Factor - metabolism
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Summary: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.
ISSN:1010-4283
1423-0380
DOI:10.1007/s13277-014-1961-6