N1, N12-Diacetylspermine Is Elevated in Colorectal Cancer and Promotes Proliferation through the miR-559/CBS Axis in Cancer Cell Lines.
N1, N12-Diacetylspermine Is Elevated in Colorectal Cancer and Promotes Proliferation through the miR-559/CBS Axis in Cancer Cell Lines.
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N1、N12-二乙酰精胺在结直肠癌中升高，并通过癌细胞系中的 miR-559/CBS 轴促进增殖
DOI：
10.1155/2021/6665704
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发表时间：
2021
影响因子：
--
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Mu T;Chu T;Li W;Dong Q;Liu Y
N1, N12-Diacetylspermine (DiAcSpm) has been reported to be upregulated in the urine of cancer patients. Mass spectrometry has shown elevated DiAcSpm expressions in colorectal cancer (CRC) tissues. However, the diagnostic application of DiAcSpm is not available due to a lack of diagnostic grade antibodies. Also, its biological roles in CRC cells remain unexplored. In the present study, we developed an antibody that directly detected DiAcSpm expression in paraffin-embedded tissues. We also characterized its biological characteristics and underlying mechanisms. Polyclonal antibodies were generated by immunizing animals with a synthetic product of DiAcSpm. Antibody DAS AB016 showed strong sensitivity against DiAcSpm in CRC tissues. Immunohistochemistry results showed that DiAcSpm expression was significantly elevated in CRC tissues. High levels of DiAcSpm correlated with the clinical stage and Ki67 index. DiAcSpm treatment increased levels of proliferation, cell cycle progression, and cyclin D1 and cyclin E proteins in CRC cell lines, SW480 and Caco-2. DiAcSpm also upregulated ATP production in these two cell lines. RNA-sequencing showed that DiAcSpm downregulated miR-559, which was confirmed using RT-qPCR. The luciferase reporter assay, western blotting, and RT-qPCR showed that cystathionine β-synthase (CBS) was the target of miR-559. miR-559 inhibited, while CBS accelerated, CRC proliferation. In addition, CBS siRNA knockdown blocked the biological effects of DiAcSpm on CRC cells. In conclusion, DiAcSpm was found to be increased in CRC tissues using a newly developed antibody. DiAcSpm accelerated CRC proliferation by regulating the miR-559/CBS axis.
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影响因子：
11.2
作者：
Phillips CM;Zatarain JR;Nicholls ME;Porter C;Widen SG;Thanki K;Johnson P;Jawad MU;Moyer MP;Randall JW;Hellmich JL;Maskey M;Qiu S;Wood TG;Druzhyna N;Szczesny B;Módis K;Szabo C;Chao C;Hellmich MR
通讯作者：
Hellmich MR
影响因子：
4.6
作者：
Ignaternko, NA;Zhang, H;Gerner, EW
通讯作者：
Gerner, EW
N1,N12-二乙酰精胺作为早期和晚期结直肠癌和乳腺癌的一种敏感而特异的新型标记物
影响因子：
11.5
作者：
Hiramatsu, K;Takahashi, K;Kawakita, M
通讯作者：
Kawakita, M
开发一种灵敏、准确的酶联免疫吸附测定（ELISA）系统，用于替代高效液相色谱法测定人体尿液中的 N1,N12-二乙酰精胺
影响因子：
2.7
作者：
Hiramatsu, K;Miura, H;Kawakita, M
通讯作者：
Kawakita, M
DOI：
10.1038/s41568-018-0050-3
发表时间：
2018-11
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Casero RA Jr;Murray Stewart T;Pegg AE
通讯作者：
Pegg AE