Effect of rs67085638 in long non‐coding RNA (CCAT1) on colon cancer chemoresistance to paclitaxel through modulating the microRNA‐24‐3p and FSCN1

Abstract

It has been reported that rs67085638 in long non‐coding RNAs (lncRNA)‐CCAT1 was associated with the risk of tumorigenesis. Also, CCAT1 could affect chemoresistance of cancer cells to paclitaxel (PTX) via regulating miR‐24‐3p and FSCN1 expression. In this study, we aimed to investigate the effect of rs67085638 on the expression of CCAT1/miR‐24‐3p/FSCN1 and the response of colon cancer to the treatment of PTX. 48 colon cancer patients were recruited and grouped by their genotypes of rs67085638 polymorphism as a CC group (N = 28) and a CT group (N = 20). PCR analysis, IHC assay and Western blot, TUNEL assay and flow cytometry were conducted. LncRNA‐CCAT1 and FSCN1 mRNA/protein were overexpressed, whereas miR‐24‐3p was down‐regulated in the CT‐genotyped patients and cells compared with those in the CC‐genotyped patients and cells. The survival of colon cancer cells was decreased, whereas the apoptosis of colon cancer cells was increased by PTX treatment in a dose‐dependent manner. MiR‐24‐3p was validated to target lncRNA‐CCAT1 and FSCN1 mRNA, and the overexpression of CCAT1 could reduce the expression of miR‐24‐3p although elevating the expression of FSCN1. Knockdown of lncRNA‐CCAT1 partly reversed the suppressed growth of CT‐genotyped tumours. And the knockdown of lncRNA‐CCAT1 partly reversed the dysregulation of lncRNA‐CCAT1 and FSCN1 mRNA/protein in rs67085638‐CT + NC shRNA mice. The findings of this study demonstrated that the presence of the minor allele of rs67085638 increased the expression of CCAT1 and accordingly enhanced the resistance to PTX. Down‐regulation of CCAT1 significantly re‐stored the sensitivity to PTX of colon cancer cells.