More and more long non-coding RNA (lncRNA) might be serve as molecular biomarkers for tumor cell progression. HOTTIP has been recently revealed as oncogenic regulator in several cancers. However, it remains unclear about whether and how HOTTIP regulates Colorectal cancer (CRC). In the present study, we assayed the expression of HOTTIP in CRC tissues and cell lines, and detected CRC cells (HCT-116 and SW620) proliferation, migration, and apoptosis when HOTTIP was knocked down. Furthermore, we discovered the underlying mechanism. The level of HOTTIP was higher in CRC tissues and in CRC cells compared with adjacent normal tissues and normal colon tissue cell. Knockdown of HOTTIP inhibited the cell proliferation migration and induced apoptosis in HCT-116 and SW620 cell lines. In addition, luciferase reporter assay suggested that knockdown of HOTTIP could target decreasing the expression of Serum- and glucocorticoid-inducible kinase 1 (SGK1) gene, and we subsequently verified that up-regulation of the SGK1 gene promoted cell proliferation and migration and inhibited cell apoptosis in HCT-116 and SW620 cell lines. Furthermore, Knockdown of HOTTIP significantly suppressed the expression of GSK3β, β-catenin, c-myc, Vimentin and MMP-7, and increased the expression of E-cadherin, FoxO3a, p27 and Bim proteins in HCT-116 and SW620 cell lines, and up-regulation of the SGK1 emerged the opposite effect with knockdown of HOTTIP. The data described in this study suggest that HOTTIP may be an oncogene and a potential target in CRC.
Keywords: Apoptosis; Colorectal cancer; HOTTIP; Migration; Proliferation; SGK1.
Copyright © 2017. Published by Elsevier Masson SAS.