This study aimed to analyze the relation between long noncoding RNA (lncRNA) LINCE00630 and radio-resistance and elucidate the underlying mechanism. Relative expression of LINC00630, BEX1, and DNMT3B in colorectal cancer (CRC) cells and clinical samples was determined by real-time PCR. Prognosis in respect of LINC00630 expression was analyzed by Kaplan-Meier survival curve. LINC00630 and BEX1 were specifically silenced by shRNAs. Cell viability and growth were analyzed by MTT and clonogenic assays, respectively. Cell apoptosis was measure by both caspase-3 activity and flow cytometry. Association between EZH2 with LINC00630 and BEX1 promoter was determined by RNA immunoprecipitation and chromatin immunoprecipitation. BEX1 and DNMT3B proteins were quantified by Western blot. We demonstrated the elevated LINC00630 correlated with radio-resistance and poorer prognosis in CRC. Knockdown of LINC00630 significantly improved the sensitivity of CRC cells to irradiation. Mechanistically, LINC00630 in complex with EZH2 negatively regulated BEX1 through promoter DNA methylation. BEX1 silencing greatly restored the cell viability and suppressed cell apoptosis, which were elicited by LINC00630 deficiency in response to irradiation. Our data uncovered the contribution of elevated LINC00630 to radio-resistance in CRC, which was predominately mediated by epigenetically repressed BEX1.
Keywords: BEX1; EZH2; LINC00630; colorectal cancer; methylation.
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