Long Noncoding Rna Ccat2 Cooperates With Mir-145 And Mir-21 To Regulate Colon Cancer Stem Cells

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LAColon cancer-associated transcript-2 (CCAT2), a long noncoding RNA (lncRNA), has been reported to be over-expressed in colorectal cancer to promote tumor growth and metastasis and also reduces sensitivity to chemotherapy, a property related to cancer stem cells (CSCs). MicroRNAs, small endogenous noncoding RNAs, negatively control the expression of target genes by cleaving mRNA or through translation repression. We have recently reported cooperation of miR-21 and miR-145 to regulate colon CSCs proliferation and differentiation. Down-regulation of miR-21 enhances CSC enriched chemo-resistant colon cancer cells’ susceptibility to chemo- therapeutic regimens. Although both CCAT2 and miR-21 increase WNT signaling activity and reduce chemosensitivity to 5-FU, a critical evidence on how CCAT2 regulates stemness leading to chemo-resistance is lacking. The primary goal of this investigation was to examine whether CCAT2 associates with miR-145 and miR-21 and whether this association plays a role in regulating stemness of colon cancer cells. We have observed that CCAT2 transcript level is dependent on p53 expression and activity, as evidenced by a marked increase in CCAT2 expression in p53 wild type harboring HCT-116 colon cancer cells compared with p53 null HCT-116 and p53 mutant HT-29 cells. We further revealed that knockdown of CCAT2 increased the expression of miR-145 and negatively regulates miR-21 in HCT-116 cells and impairs proliferation and differentiation of these cells. On the other hand, upregulation of CCAT2 induces proliferation of HCT-116 cells and also increases the expression of CSC markers CD44 and CD166. We have also observed that miR-145 and miR-21 cooperation plays a role in regulating colon cancer stem cells by down-regulating Sox2 and increased activity of Wnt/β-catenin pathway. Our current results suggest that lncRNA CCAT2 cooperates with miR-145 and miR-21 to regulate colon cancer stem cells, which provides a potential therapeutic target for chemoresistance in colorectal cancer.Citation Format: Yingjie Yu, Pratima Nangia-Makker, Lulu Farhana, Adhip P. N. Majumdar. Long noncoding RNA CCAT2 cooperates with miR-145 and miR-21 to regulate colon cancer stem cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 986.