Long noncoding RNA LINC00673 epigenetically suppresses KLF4 by interacting with EZH2 and DNMT1 in gastric cancer
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Ming-Chen Ba1, Hui Long2, Shu-Zhong Cui1, Yuan-Feng Gong1, Zhao-Fei Yan1, Yin-Bing Wu1 and Yi-Nuo Tu1
1Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, P.R. China
2Department of Pharmacy, Guangzhou Dermatology Institute, Guangzhou 510095, P.R. China
Ming-Chen Ba, email: [email protected]
Hui Long, email: [email protected]
Keywords: long noncoding RNA; LINC00673; DNMT1; EZH2; KLF4
Received: July 04, 2017 Accepted: August 04, 2017 Published: September 18, 2017
Long non-coding RNAs (lncRNAs), a variety of transcripts without protein coding ability, have recently been reported to play vital roles in gastric cancer (GC) development and progression. However, the biological role of long non-coding RNA LINC00673 in GC is not fully known. In the study, we found that LINC00673 expression was dramatically higher in gastric cancer tissues compared with adjacent normal tissues, and positively associated with lymph node metastasis, distant metastasis and TNM stage in patients. Higher LINC00673 expression predicted poor disease-free survival (DFS) and overall survival (OS) in GC patients. By univariate and multivariate Cox analysis, the results confirmed that higher LINC00673 expression was an independent risk factor of prognosis in patients. Knockdown of endogenous LINC00673 significantly inhibited cell proliferation, colony formation number, cell migration and invasion in GC. Furthermore, knockdown of endogenous LINC00673 reduced the expression levels of PCNA, CyclinD1 and CDK2 in GC cells. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) proved that LINC00673 suppressed KLF4 expression by interacting with EZH2 and DNMT1 in GC cells. Moreover, we confirmed that LINC00673 promoted cell proliferation and invasion by partly repressing KLF4 expression in GC. Taken together, these results indicated that LINC00673 may be a prognostic biomarker and therapeutic target for GC patients.
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