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

Colorectal cancer (CRC) represents a common malignancy in gastrointestinal tract. Iodine-125 (125I) seed implantation is an emerging treatment technology for unresectable tumors. This study investigated the mechanism of 125I seed in the function of CRC cells. | Ren et al. BMC Cancer 2022 22 49 https doi.org 10.1186 s12885-021-09141-4 RESEARCH Open Access Iodine-125 seed represses the growth and facilitates the apoptosis of colorectal cancer cells by suppressing the methylation of miR-615 promoter Fenghai Ren1 Baojun Li2 Chao Wang3 Yanbo Wang1 and Binbin Cui4 Abstract Background Colorectal cancer CRC represents a common malignancy in gastrointestinal tract. Iodine-125 125I seed implantation is an emerging treatment technology for unresectable tumors. This study investigated the mecha- nism of 125I seed in the function of CRC cells. Methods The CRC cells were irradiated with different doses of 125I 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 xeno- graft tumor model irradiated by 125I seed was established in nude mice. The methylation of miR-615 Ki67 expression and CRC cell apoptosis were detected. Results 125I 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. 125I 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 125I seed treatment. In vivo experiments confirmed that 125 I 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 regula- tory downstream pathway .