Nei Endonuclease VIII-Like1 (NEIL1) Inhibits Apoptosis of Human Colorectal Cancer Cells
Nei Endonuclease VIII-Like1 (NEIL1) Inhibits Apoptosis of Human Colorectal Cancer Cells
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Nei 核酸内切酶 VIII-Like1 (NEIL1) 抑制人结直肠癌细胞凋亡
DOI：
10.1155/2020/5053975
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发表时间：
2020-06-27
影响因子：
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通讯作者：
Han, Jiming
中科院分区：
文献类型：
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作者：
Xue, Wanjuan;Liu, Yongcheng;Han, Jiming
本研究旨在探讨Nei核酸内切酶VIII样1（NEIL 1）在结直肠癌（CRC）发病机制中的作用。对人CRC（HCT 116和SW 480）细胞进行NEIL 1的siRNA沉默和重组质粒过表达。转染siNEIL 1后，细胞生长明显受到抑制。它还增加了人CRC细胞中Bax的表达水平，同时降低了Bcl-2的表达水平，导致Bax/Bcl-2平衡朝向凋亡。caspase-9信号通路促进细胞凋亡。另一方面，NEIL 1的高表达促进了细胞的存活，减少了细胞的凋亡，诱导了Bax/Bcl-2的平衡，使人结肠癌细胞抗凋亡。此外，caspase-9信号通路抑制细胞凋亡，与通过下调NEIL 1表达获得的结果相反。此外，NEIL 1受miR-7- 5 p负调控，表明miR-7- 5 p在转录后抑制NEIL 1的表达。miR-7- 5 p的过表达逆转了NEIL 1对这些CRC细胞的作用。总之，NEIL 1促进CRC细胞的增殖，其受miR-7- 5 p负调控。这些发现表明NEIL 1是CRC的潜在治疗靶点。
The study is aimed at investigating the role of Nei endonuclease VIII-like1 (NEIL1) in the pathogenesis of colorectal cancer (CRC). The human CRC (HCT116 and SW480) cells were subjected to the siRNA silencing and recombinant plasmid overexpression of NEIL1. Transfection of siNEIL1 significantly inhibited the cell growth. It also increased the Bax expression levels, while it decreased the Bcl-2 expression levels in human CRC cells, leading the Bax/Bcl-2 balance toward apoptosis. Moreover, the apoptosis was promoted through the caspase-9 signaling pathway. One the other hand, high expression of NEIL1 promoted the cell viability and reduced the apoptosis, inducing the balance of Bax/Bcl-2 in the human colon cancer cells to be antiapoptotic. In addition, the caspase-9 signaling pathway inhibited apoptosis, contrary to the results obtained by downregulating NEIL1 expression. Furthermore, NEIL1 was negatively regulated by miR-7-5p, indicating that miR-7-5p inhibited the NEIL1 expression after transcription. Overexpression of miR-7-5p reversed the effects of NEIL1 on these CRC cells. In conclusion, NEIL1 promotes the proliferation of CRC cells, which is regulated negatively by miR-7-5p. These findings suggest that NEIL1 is a potential therapeutic target for CRC.