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Tumor Biology

, Volume 35, Issue 7, pp 7097–7103 | Cite as

Stat3 inhibits Beclin 1 expression through recruitment of HDAC3 in nonsmall cell lung cancer cells

  • Li-Jun Miao
  • Feng-Xiang Huang
  • Zhen-Tao Sun
  • Rui-Xia Zhang
  • Shi-Fu Huang
  • Jing Wang
Research Article

Abstract

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.

Keywords

Nonsmall cell lung cancer Stat3 Beclin 1 HDAC3 

Notes

Acknowledgments

We thank Dr. Yan Zuo-Qin for providing the CA-Stat3 plasmid.

Conflicts of interest

None of the authors has any potential conflicts of interest

Supplementary material

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Supplementary Figure 1

Regulation of Beclin 1 by IL-6 in lung cancer cells. (A-B) Relative mRNA levels of Beclin 1 in AGS (A) and NCI-H1650 (B) cells treated with IL-6 (10 ng/ml) at different time as indicated. (GIF 2 kb)

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High Resolution Image (TIFF 339 kb)
13277_2014_1961_Fig6_ESM.gif (5 kb)
Supplementary Figure 2

Regulation of Beclin 1 by dominant-negative Stat3 in lung cancer cells. (A-B) mRNA and protein levels of Beclin 1 were analyzed by Real-time PCR (A) and western blot (B) in AGS cells transfected with empty vector (EV) or a dominant-negative Stat3 mutant (DN-Stat3), for 24 or 36 hr, respectively. (C-D) mRNA and protein levels of Beclin 1 were analyzed by Real-time PCR (C) and western blot (D) in NCI-H1650 cells transfected with empty vector (EV) or a dominant-negative Stat3 mutant (DN-Stat3), for 24 or 36 hr, respectively. Plasmids containing green fluorescent protein (GFP) gene were co-transfected to evaluate the efficiency of transfection. (GIF 4 kb)

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High Resolution Image (TIFF 476 kb)
13277_2014_1961_Fig7_ESM.gif (6 kb)
Supplementary Figure 3

Inhibitory roles of Stat3 on Beclin 1 expression relies on its recruitment of HDAC3. (A) mRNA levels of Beclin 1 in NCI-H1650 cells treated with vehicle control (PBS) or IL-6 (10ng/ml). Cells were pre-transfected with siRNA targeting HDAC3 or nonspecific negative controls (NC) for 24 hr. (B-C) mRNA levels of Beclin 1 in AGS cells treated with vehicle control (PBS) or IL-6 (10ng/ml). Cells were pre-transfected with siRNA targeting HDAC1 (B), HDAC2 (C) or nonspecific negative controls (NC) for 24 hr. Representative protein levels of HDAC1 and HDAC2 were displayed as indicated. (GIF 5 kb)

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High Resolution Image (TIFF 612 kb)
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Supplementary Figure 4

Down-regulation of p53 by Stat3 in lung cancer cells. (A)Protein levels of p53 in AGS cells treated with vehicle control (PBS) or IL-6 (10ng/ml). Cells were pre-transfected with siRNA targeting HDAC3 or nonspecific negative controls (NC) for 24 hr. (B) Protein levels of p53 in AGS cells transfected with empty vector (EV) or constitutive activated Stat3 (CA-Stat3). Cells were pre-transfected with siRNA targeting HDAC3 or nonspecific negative controls (NC) for 24 hr. (GIF 3 kb)

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High Resolution Image (TIFF 394 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Li-Jun Miao
    • 1
  • Feng-Xiang Huang
    • 1
  • Zhen-Tao Sun
    • 2
  • Rui-Xia Zhang
    • 1
  • Shi-Fu Huang
    • 1
  • Jing Wang
    • 1
  1. 1.Department of Respiratory MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  2. 2.Department of AnesthesiaThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

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