Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University, Changchun, China.
Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, China.
J Cell Mol Med. 2020 Mar;24(5):3149-3156. doi: 10.1111/jcmm.14985. Epub 2020 Jan 22.
Recently, many studies have shown that microRNA (miR)-612 is involved in cancer progression. However, the role of miR-612 in cervical cancer remains unclear. The present study aims to investigate the biological effects of miR-612 on cervical cancer. The expression of miR-612 in cervical cancer tissues and cell lines was analysed by quantitative reverse transcription-polymerase chain reaction. The effect of miR-612 cell proliferation, migration, invasion and apoptosis was studied by appropriate methods. Protein expression was determined by Western blot analyses. Bioinformatics analysis and luciferase reporter assays were performed to clarify the relationship between miR-612 and nin one binding protein (NOB1). A xenograft model was established to examine the role of miR-612 in vivo tumorigenesis. Cervical cancer tissues and cell lines showed down-regulation of miR-612 expression, which was associated with the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage and lymph node metastasis. Functional assays revealed that miR-612 overexpression significantly suppressed cervical cancer cell proliferation, migration and invasion in vitro and delayed tumour growth in vivo. Mechanically, miR-612 targeted NOB1 in cervical cancer cells, revealing a negative correlation between miR-612 and NOB1in cervical cancer samples. NOB1 overexpression partially reversed the inhibitory effects of miR-612 overexpression in cervical cancer cells. Taken together, these findings indicate that miR-612 functions as a tumour suppressor in cervical cancer and suggest that miR-612 may be a potential target in the therapeutic intervention of this malignancy.
最近,许多研究表明 microRNA(miR)-612 参与了癌症的进展。然而,miR-612 在宫颈癌中的作用仍不清楚。本研究旨在探讨 miR-612 对宫颈癌的生物学效应。通过定量逆转录聚合酶链反应分析了 miR-612 在宫颈癌组织和细胞系中的表达。通过适当的方法研究了 miR-612 对细胞增殖、迁移、侵袭和凋亡的影响。通过 Western blot 分析测定蛋白质表达。进行生物信息学分析和荧光素酶报告基因检测以阐明 miR-612 与 nin one 结合蛋白(NOB1)之间的关系。建立异种移植模型以研究 miR-612 在体内肿瘤发生中的作用。宫颈癌组织和细胞系显示 miR-612 表达下调,其与国际妇产科联合会(FIGO)分期和淋巴结转移有关。功能测定表明,miR-612 过表达可显著抑制宫颈癌细胞的体外增殖、迁移和侵袭,并延缓体内肿瘤生长。机制上,miR-612 在宫颈癌细胞中靶向 NOB1,揭示了 miR-612 和 NOB1 在宫颈癌样本中的负相关。NOB1 过表达部分逆转了 miR-612 过表达对宫颈癌细胞的抑制作用。综上所述,这些发现表明 miR-612 在宫颈癌中作为肿瘤抑制因子发挥作用,并提示 miR-612 可能是该恶性肿瘤治疗干预的潜在靶点。