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微小RNA-329-3p靶向丝裂原活化蛋白激酶1以抑制宫颈癌中的细胞增殖、迁移和侵袭。

MicroRNA-329-3p targets MAPK1 to suppress cell proliferation, migration and invasion in cervical cancer.

作者信息

Li Wenfeng, Liang Jingjing, Zhang Zhechao, Lou Hongyan, Zhao Liang, Xu Yunsheng, Ou Rongying

机构信息

Laboratory for Advanced Interdisciplinary Research, Center for Personalized Medicine/Institutes of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

出版信息

Oncol Rep. 2017 May;37(5):2743-2750. doi: 10.3892/or.2017.5555. Epub 2017 Apr 5.

Abstract

Cervical cancer is the second most common gynecological cancer worldwide and remains as one of the leading causes of cancer-related death among women. Despite great progress in the treatment of cervical cancer, the 5-year overall survival rate for patients with this disease remains unsatisfactory. Over the past decade, an increasing number of studies indicate a central role for microRNAs in the initiation and progression of cervical cancer. microRNA‑329-3p (miR-329-3p) has been studied in many types of human cancer; however, the expression level, biological role and the underlying mechanism of miR-329-3p in cervical cancer has not yet been investigated. In the present study, we found that the expression levels of miR-329-3p were reduced in both cervical cancer tissues and cell lines. Low miR-329-3p expression was negatively correlated with histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and lymph node metastasis of cervical cancer patients. In addition, upregulation of miR‑329-3p suppressed cell proliferation, migration and invasion of cervical cancer. Furthermore, MAPK1 was identified as a direct target gene of miR-329-3p. MAPK1 was significantly upregulated in cervical cancer tissues and was inversely correlated with miR-329-3p expression in the cervical cancer tissues. Silencing of MAPK1 by RNA interference mimicked the effects of miR-329-3p overexpression on cell proliferation, migration and invasion in cervical cancer. Moreover, rescue experiments showed that restoration of the expression of MAPK1 reversed the effects of miR‑329-3p overexpression in cervical cancer cells. Taken together, these findings suggest that miR-329-3p has a critical tumor-suppressive roles by directly targeting MAPK1 in cervical cancer, and it may be investigated as a novel therapeutic target for the treatment of patients with this disease.

摘要

宫颈癌是全球第二常见的妇科癌症,仍是女性癌症相关死亡的主要原因之一。尽管宫颈癌治疗取得了巨大进展,但该疾病患者的5年总生存率仍不尽人意。在过去十年中,越来越多的研究表明微小RNA在宫颈癌的发生和发展中起核心作用。微小RNA-329-3p(miR-329-3p)已在多种人类癌症中得到研究;然而,miR-329-3p在宫颈癌中的表达水平、生物学作用及潜在机制尚未得到研究。在本研究中,我们发现miR-329-3p在宫颈癌组织和细胞系中的表达水平均降低。miR-329-3p低表达与宫颈癌患者的组织学分级、国际妇产科联盟(FIGO)分期及淋巴结转移呈负相关。此外,miR-329-3p的上调抑制了宫颈癌细胞的增殖、迁移和侵袭。此外,丝裂原活化蛋白激酶1(MAPK1)被鉴定为miR-329-3p的直接靶基因。MAPK1在宫颈癌组织中显著上调,且与宫颈癌组织中miR-329-3p的表达呈负相关。通过RNA干扰沉默MAPK1模拟了miR-329-3p过表达对宫颈癌细胞增殖、迁移和侵袭的影响。此外,挽救实验表明,恢复MAPK1的表达可逆转miR-329-3p过表达对宫颈癌细胞的影响。综上所述,这些发现表明miR-329-3p通过直接靶向MAPK1在宫颈癌中发挥关键的肿瘤抑制作用,它可能作为治疗该疾病患者的新型治疗靶点进行研究。

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