Research Papers:

Hypermethylated in cancer 1(HIC1) suppresses non-small cell lung cancer progression by targeting interleukin-6/Stat3 pathway

Xiumin Wang, Yingying Wang, Gang Xiao, Jinglong Wang, Lidong Zu, Mingang Hao, Xueqing Sun, Yujie Fu, Guohong Hu and Jianhua Wang _

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Oncotarget. 2016; 7:30350-30364. https://doi.org/10.18632/oncotarget.8734

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Xiumin Wang1,*, Yingying Wang1,*, Gang Xiao1, Jinglong Wang1, Lidong Zu1, Mingang Hao1, Xueqing Sun1, Yujie Fu3, Guohong Hu4 and Jianhua Wang2

1 Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China

2 Cancer institute, Fudan University Shanghai Cancer Center, Shanghai, China

3 Department of Chest Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

4 Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

* These authors have contributted equally to this work

Correspondence to:

Jianhua Wang, email:

Keywords: HIC1/IL-6 axis, hypermethylation, NSCLC

Received: December 13, 2015 Accepted: April 06, 2016 Published: April 14, 2016


Non-small cell lung cancer (NSCLC), which accounts for more than 80% of lung cancers, is a leading cause of cancer mortality worldwide. However, the mechanism underlying its progression remains unclear. Here we found that HIC1 promoter was heavily methylated in NSCLC cell lines and tissues contributing to its low expression compared to normal controls. Restoring HIC1 expression inhibited migration, invasion and promoted inducible apoptosis of NSCLC cells. Notably, HIC1 is a tumor suppressor through inhibiting the transcription of IL-6 by sequence-specific binding on its promoter. Restoring IL-6 expression could partially rescue these phenotypes induced by HIC1 in vitro and in vivo. Mechanistic analyses show that autocrine secretion of IL-6 induced by loss of HIC1 activated STAT3 through IL-6/JAK pathway and was associated with NSCLC progression. The HIC1/IL-6 axis may serve as a prognostic biomarker and provide an attractive therapeutic target for NSCLC.

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