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miR-940的上调通过抑制p27和PTEN促进人类宫颈癌进展。

miR-940 upregulation contributes to human cervical cancer progression through p27 and PTEN inhibition.

作者信息

Su Ke, Wang Chun-Fang, Zhang Ying, Cai Yu-Jie, Zhang Yan-Yan, Zhao Qian

机构信息

Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

出版信息

Int J Oncol. 2017 Apr;50(4):1211-1220. doi: 10.3892/ijo.2017.3897. Epub 2017 Mar 7.

DOI:10.3892/ijo.2017.3897
PMID:28350106
Abstract

Cervical cancer is considered as a gynecological malignancy accompanied with high rates of mortality across the world. Effective diagnostic, prognostic markers as well as therapeutic targets are necessary to be explored. The p27 and PTEN are known to modulate tumor cell growth and proliferation. However, the molecular mechanisms modulating these genes have not completely been elucidated. In our study, real-time (RT) quantitative PCR indicated that miR‑940 levels were upregulated in human cervical cancer tissue samples and cell lines. Overexpression of miR‑940 could reduce overall survival in patients. Ectopic miR‑940 accelerated cervical cancer cell growth, proliferation and cell cycle arrest in vitro as well as tumor formation in vivo. p27 and PTEN were evidenced as direct targets for miR‑940 and inhibition of p27 and PTEN recovered the suppressive function of miR‑940-silenced cell towards to proliferation and tumorigenicity in cervical cancer cells. In addition, miR‑940 expression was inversely associated with p27 and PTEN expression levels and actively with cyclin D1 in cervical cancer specimens. The results from our study demonstrated that miR‑940 regulated p27 and PTEN post-transcriptionally and might play a significant role in cervical cancer development and progression. Thus, miR‑940 might provide a potential value as therapeutic target for cervical cancer treatment in future.

摘要

宫颈癌被认为是一种妇科恶性肿瘤,在全球范围内死亡率很高。有必要探索有效的诊断、预后标志物以及治疗靶点。已知p27和PTEN可调节肿瘤细胞的生长和增殖。然而,调节这些基因的分子机制尚未完全阐明。在我们的研究中,实时定量PCR表明,miR-940在人宫颈癌组织样本和细胞系中的水平上调。miR-940的过表达会降低患者的总生存率。异位表达miR-940在体外可加速宫颈癌细胞的生长、增殖和细胞周期停滞,在体内可促进肿瘤形成。p27和PTEN被证明是miR-940的直接靶点,抑制p27和PTEN可恢复miR-940沉默细胞对宫颈癌细胞增殖和致瘤性的抑制作用。此外,在宫颈癌标本中,miR-940的表达与p27和PTEN的表达水平呈负相关,与细胞周期蛋白D1呈正相关。我们的研究结果表明,miR-940在转录后调节p27和PTEN,可能在宫颈癌的发生和发展中起重要作用。因此,miR-940未来可能作为宫颈癌治疗的潜在靶点具有重要价值。

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