Li Wenfeng, Liang Jingjing, Zhang Zhechao, Lou Hongyan, Zhao Liang, Xu Yunsheng, Ou Rongying
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.
Oncol Rep. 2017 May;37(5):2743-2750. doi: 10.3892/or.2017.5555. Epub 2017 Apr 5.
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.
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。