Loss of TINCR expression promotes proliferation, metastasis through activating EpCAM cleavage in colorectal cancer
Metrics: PDF 2130 views | HTML 2583 views | ?
Zuo-yang Zhang1,*, Yan-xia Lu1,*, Zhe-ying Zhang1, Ya-ya Chang1, Lin Zheng1, Li Yuan1,2, Fan Zhang1, Yu-han Hu1, Wen-juan Zhang1, Xue-nong Li1
1Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
2Department of Pathology, Guangzhou Women and Children’s Medical Center, Guangzhou 510515, China
*These authors contributed equally to this work
Xue-nong Li, e-mail: [email protected]
Keywords: TINCR, EpCAM, c-Myc, sp1, colorectal cancer
Received: November 03, 2015 Accepted: February 15, 2016 Published: March 17, 2016
Long non-coding RNAs (lncRNAs) are involved in kinds of human diseases, including colorectal cancer (CRC). TINCR, a 3.7 kb long non coding RNA, was associated with cell differentiation in keratinocyte and gastric cancer cells. However, little is known about the role of TINCR in regulation CRC progression. Here, we showed that lncRNA TINCR was associated with CRC proliferation and metastasis. TINCR was statistically downregulated in CRC tissues and metastatic CRC cell lines compared with their counterparts. TINCR was reversely correlated with CRC progression and promoted tumor cells growth, metastasis in vivo and in vitro. While overexpression of TINCR had opposite effect. In addition, we also found that TINCR specifically bound to EpCAM through RNA IP and RNA pull down assays. Loss of TINCR promoted hydrolysis of EpCAM and then released EpICD, subsequently, activated the Wnt/β-catenin pathway. Further studies shown that c-Myc repressed the expression of TINCR through repressing sp1 transcriptive activity, which established a positive feedback loop controlling c-Myc and TINCR expression. These findings elucidate that loss of TINCR expression promotes proliferation and metastasis in CRC and it could be considered as a potential cancer suppressor gene.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.