MiR-9-1 Suppresses Cell Proliferation and Promotes Apoptosis by Targeting UHRF1 in Lung Cancer.
MiR-9-1 Suppresses Cell Proliferation and Promotes Apoptosis by Targeting UHRF1 in Lung Cancer.
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DOI：
10.1177/15330338211041191
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发表时间：
2021-01
影响因子：
2.8
通讯作者：
Fu D
中科院分区：
文献类型：
--
作者：
Jia CY;Xiang W;Liu JB;Jiang GX;Sun F;Wu JJ;Yang XL;Xin R;Shi Y;Zhang DD;Li W;Zuberi Z;Zhang J;Lu GX;Wang HM;Wang PY;Yu F;Lv ZW;Ma YS;Fu D
肺癌被列为世界上最常见的癌症相关死亡原因，尽管诊断有所改善，化疗和靶向治疗也有所发展。MicroRNAs控制着包括发育和癌症在内的生理和病理过程。建立了microRNA-9 to 1(miR-9 to 1)在肺癌细胞系中的过表达模型，发现miR-9 to 1能显著抑制肺癌细胞株的增殖率、体外集落形成和对A549细胞的裸鼠致瘤性。MiR-9 to 1抑制uhrf1使细胞周期停滞于G1期，p15、p16和p21在mRNA和蛋白水平重新表达。在A549细胞中，uhrf1表达的沉默导致与miR-9 to 1感染相似的p15、p16、p21的重新表达。因此，我们得出结论：uhrf1是miR-9 to 1通过uhrf1介导的肿瘤抑制基因p15、p16和p21的再表达而抑制细胞增殖的新靶点。
Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 to 1. The inhibition of UHRF1 by miR-9 to 1 causes G1 arrest and p15, p16, and p21 were re-expressed in miR-9 to 1 group in mRNA level and protein level. Silence of UHRF1 expression in A549 cells resulted in the similar re-expression of p15, p16, p21 which is similar with miR-9 to 1 infection. Therefore, we concluded that UHRF1 is a new target for miR-9 to 1 to suppress cell proliferation by re-expression of tumor suppressors p15, p16, and p21 mediated by UHRF1.
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