期刊
ONCOTARGET
卷 7, 期 21, 页码 30350-30364出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8734
关键词
HIC1/IL-6 axis; hypermethylation; NSCLC
资金
- National Natural funding of China [81071747, 81272404]
- National key program (973) for Basic Research of China [2011CB510106]
- Program for Professor of Special Appointment at Shanghai Institutions of Higher Learning
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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