Iodine-125 seed represses the growth and facilitates the apoptosis of colorectal cancer cells by suppressing the methylation of miR-615 promoter

作者：Ren, Fenghai; Li, Baojun; Wang, Chao; Wang, Yanbo; Cui, Binbin^*

来源：BMC CANCER, 2022, 22(1): 49.

DOI：10.1186/s12885-021-09141-4

• Iodine-125 seed
• microR-615
• Methylation
• Colorectal cancer
• 5-AZA
• MAPK pathway

Background Colorectal cancer (CRC) represents a common malignancy in gastrointestinal tract. Iodine-125 (I-125) seed implantation is an emerging treatment technology for unresectable tumors. This study investigated the mechanism of I-125 seed in the function of CRC cells. Methods The CRC cells were irradiated with different doses of I-125 seed (0.4, 0.6 and 0.8 mCi). miR-615 expression in CRC tissues and adjacent tissues was detected by RT-qPCR. miR-615 expression was intervened with miR-615 mimic or miR-615 inhibitor, and then the CRC cells were treated with 5-AZA (methylation inhibitor). The CRC cell growth, invasion and apoptosis were measured. The methylation level of miR-615 promoter region was detected. The xenograft tumor model irradiated by I-125 seed was established in nude mice. The methylation of miR-615, Ki67 expression and CRC cell apoptosis were detected. Results I-125 seed irradiation repressed the growth and facilitated apoptosis of CRC cells in a dose-dependent manner. Compared with adjacent tissues, miR-615 expression in CRC tissues was downregulated and miR-615 was poorly expressed in CRC cells. Overexpression of miR-615 suppressed the growth of CRC cells. I-125 seed-irradiated CRC cells showed increased miR-615 expression, reduced growth rate and enhanced apoptosis. The methylation level of miR-615 promoter region in CRC cells was decreased after I-125 seed treatment. In vivo experiments confirmed that I-125 seed-irradiated xenograft tumors showed reduced methylation of the miR-615 promoter and increased miR-615 expression, as well as decreased Ki67 expression and enhanced apoptosis. The target genes of miR-615 and its regulatory downstream pathway were further predicted by bioinformatics analysis. Conclusions I-125 seed repressed the growth and facilitated the apoptosis of CRC cells by suppressing the methylation of the miR-615 promoter and thus activating miR-615 expression. The possible mechanism was that miR-615-5p targeted MAPK13, thus affecting the MAPK pathway and the progression of CRC.

• 单位
  哈尔滨医科大学