title: Loss of TINCR expression promotes proliferation, metastasis through activating EpCAM cleavage in colorectal cancer.
abstract: 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.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zuo-Yang
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Lu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zhe-Ying
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Ya-Ya
authors.initials: YY
authors.lastname: Chang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.|Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou 510515, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Hu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xue-Nong
authors.initials: XN
authors.lastname: Li
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism*; D045325:HCT116 Cells; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D062085:RNA, Long Noncoding / Q000378:metabolism*
chemical_list: C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D062085:RNA, Long Noncoding; C000618032:TINCR lncRNA, human
keywords: EpCAM; TINCR; c-Myc; colorectal cancer; sp1