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microRNA-802 通过靶向丝氨酸/精氨酸丰富剪接因子 9 抑制人宫颈癌细胞增殖并诱导细胞凋亡。

microRNA-802 inhibits cell proliferation and induces apoptosis in human cervical cancer by targeting serine/arginine-rich splicing factor 9.

机构信息

Gynecological Oncology Ward I, Gansu Provincial Cancer Hospital, Lanzhou City, Gansu Province, P. R. China.

Department of Cancer Research Institute, Cancer Affiliated Hospital of Xinjiang Medical University, Urumqi City, Xinjiang Province, P. R. China.

出版信息

J Cell Biochem. 2019 Jun;120(6):10370-10379. doi: 10.1002/jcb.28321. Epub 2018 Dec 19.

Abstract

microRNAs (miRNAs) play crucial roles in cancer development and progression by targeting mRNAs for degradation and/or translational repression. microRNA-802 (miR-802) has been reported as a tumor suppressor and its deregulation is observed in various human cancers. However, the prognostic value of miR-802 and its underlying mechanisms involved in human cervical cancer are poorly investigated. The purposes of this study were to explore the role of miR-802 in cervical cancer and to clarify the regulation of serine/arginine-rich splicing factor 9 (SRSF9) by miR-802. Here, we found that miR-802 was downregulated in both cervical cancer tissues and cell lines. Transfection of a miR-802 mimic into cervical cancer cells inhibited their proliferation and colony formation, and promoted cell cycle arrest at the G0/G1 phase and cell apoptosis. In addition, we found that miR-802 could directly target the 3'-untranslated region of SRSF9 and suppress SRSF9 expression. Rescue experiments revealed that overexpression of SRSF9 partially reversed the inhibition effect of miR-802 in cervical cancer cells. Overall, these findings demonstrate that miR-802 functions as a tumor suppressor in cervical cancer by targeting SRSF9, suggesting that miR-802 might serve as a potential therapeutic target in cervical cancer.

摘要

微小 RNA(miRNAs)通过靶向 mRNA 的降解和/或翻译抑制,在癌症的发生和发展中发挥关键作用。miR-802 已被报道为一种肿瘤抑制因子,其在各种人类癌症中存在失调。然而,miR-802 在人宫颈癌中的预后价值及其潜在机制仍研究甚少。本研究旨在探讨 miR-802 在宫颈癌中的作用,并阐明其对丝氨酸/精氨酸丰富剪接因子 9(SRSF9)的调控作用。在这里,我们发现 miR-802 在宫颈癌组织和细胞系中均下调。转染 miR-802 模拟物可抑制宫颈癌细胞的增殖和集落形成,并促进细胞周期停滞在 G0/G1 期和细胞凋亡。此外,我们发现 miR-802 可以直接靶向 SRSF9 的 3'非翻译区并抑制 SRSF9 的表达。挽救实验表明,SRSF9 的过表达部分逆转了 miR-802 对宫颈癌细胞的抑制作用。总之,这些发现表明 miR-802 通过靶向 SRSF9 在宫颈癌中发挥肿瘤抑制作用,提示 miR-802 可能成为宫颈癌的潜在治疗靶点。

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