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微小RNA-212-3p通过直接靶向丝裂原活化蛋白激酶激酶激酶3抑制高级别浆液性卵巢癌进展。

MiR-212-3p suppresses high-grade serous ovarian cancer progression by directly targeting MAP3K3.

作者信息

Zhang Lu, Zhang Ying, Wang Shasha, Tao Lin, Pang Lijuan, Fu Ruiting, Fu Yu, Liang Weihua, Li Feng, Jia Wei

机构信息

Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, The First Affiliated Hospital, Shihezi University School of Medicine Shihezi, China.

Department of Obestetrics and Gynecology, The First Affiliated Hospital School of Medicine, Shihezi University Shihezi, China.

出版信息

Am J Transl Res. 2020 Mar 15;12(3):875-888. eCollection 2020.

Abstract

MicroRNAs (miRNAs) are small regulatory non-coding RNAs that have been reported to play an important role in the tumorigenesis of many cancers. In addition, miRNAs might serve as new promising biomarkers for diagnosis and prognosis and as effective therapeutic targets for patients with such malignancies. Accordingly, the dysregulation of miR-212-3p has been reported in a variety of human cancers. However, its biological functions and molecular mechanisms high-grade serous ovarian cancer (HGSOG) remain unknown. In this study, we demonstrated that miR-212-3p interacts with MAP3K3 based on bioinformatics-based predictions. Further, MAP3K3 was identified as a direct target gene of miR-212-3p in HGSOC. In addition, overexpression of miR-212-3p in HGSOC inhibited cell proliferation, colony formation, invasion, and migration. In contrast MAP3K3 mitigated the suppressive effects of miR-212-3p on HGSOC cell proliferation, invasion, and migration. Furthermore, miR-212-3p was significantly downregulated in HGSOC tissues compared to expression in normal fallopian tube tissues and was inversely associated with MAP3K3 levels. Accordingly, low miR-212-3p expression was also correlated with poor prognosis for HGSOC patients. In conclusion, miR-212-3p might act as a suppressor of HGSOC carcinogenesis by directly targeting MAP3K3. Therefore, this miRNA could be a novel and effective target for the treatment of patients with HGSOC.

摘要

微小RNA(miRNA)是一类小的调节性非编码RNA,据报道在多种癌症的肿瘤发生过程中发挥重要作用。此外,miRNA可能作为诊断和预后的新的有前景的生物标志物,以及此类恶性肿瘤患者的有效治疗靶点。因此,已有报道称miR-212-3p在多种人类癌症中存在失调。然而,其在高级别浆液性卵巢癌(HGSOG)中的生物学功能和分子机制仍不清楚。在本研究中,基于生物信息学预测,我们证明miR-212-3p与丝裂原活化蛋白激酶激酶激酶3(MAP3K3)相互作用。此外,MAP3K3被确定为HGSOG中miR-212-3p的直接靶基因。此外,miR-212-3p在HGSOG中的过表达抑制了细胞增殖、集落形成、侵袭和迁移。相反,MAP3K3减轻了miR-212-3p对HGSOG细胞增殖、侵袭和迁移的抑制作用。此外,与正常输卵管组织中的表达相比,miR-212-3p在HGSOG组织中显著下调,并且与MAP3K3水平呈负相关。因此,miR-212-3p低表达也与HGSOG患者的不良预后相关。总之,miR-212-3p可能通过直接靶向MAP3K3而作为HGSOG致癌作用的抑制剂。因此,这种miRNA可能是治疗HGSOG患者的一种新的有效靶点。

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