Meng Fanxu, Ou Jian, Liu Jinyu, Li Xindi, Meng Yanli, Yan Ling, Deng Ping, Sun Baosheng
Department of Radiotherapy, Jilin Cancer Hospital, Changchun, Jilin 130012, P.R. China.
Exp Ther Med. 2019 Nov;18(5):3650-3658. doi: 10.3892/etm.2019.7989. Epub 2019 Sep 9.
Previously, a number of microRNAs (miRNAs) have been reported to be dysregulated in cervical cancer, and dysregulated miRNAs may play crucial roles in the development and progression of cervical cancer. Hence, investigating the detailed roles of miRNAs that are aberrantly expressed in cervical cancer and the underlying molecular mechanisms is essential for early diagnosis and effective therapeutic approaches. miRNA-877 (miR-877) was found to be downregulated in hepatocellular carcinoma and renal cell carcinoma, and function as a tumor-suppressive miRNA. However, how miR-877 exerts an effect in cervical cancer progression and its underlying molecular mechanisms remains to be elucidated. In the current study, reverse transcription-quantitative PCR was performed to determine miR-877 expression in cervical cancer tissues and cell lines. The effects of miR-877 overexpression on cervical cancer cell proliferation and invasion were evaluated using MTT and Transwell cell invasion assays. In the present study, miR-877 was significantly downregulated in cervical cancer tissues and cell lines, and the decreased expression levels of miR-877 were significantly associated with increased International Federation of Gynecology and Obstetric stage as well as increased lymph node metastasis in patients with cervical cancer. Upregulation of miR-877 using miR-877 mimics resulted in the decreased proliferation and invasion of cervical cancer cells. Metastasis-associated in colon cancer-1 (MACC1) was assessed using bioinformatics analyses to determine whether it could be a potential target gene of miR-877, and the results were confirmed using a luciferase reporter assay. Furthermore, MACC1 was markedly upregulated in cervical cancer tissues, and its level was negatively correlated with the miR-877 level. Overexpression of miR-877 resulted in decreased expression levels of MACC1 in cervical cancer cells at both the mRNA and protein levels. In addition, the functional effects of MACC1 knockdown were similar to those induced by upregulated miR-877 in cervical cancer cells. MACC1 restored miR-877 overexpression-mediated suppression of cervical cancer cell proliferation and invasion. In conclusion, miR-877 may play an antitumor role in cervical cancer by directly targeting MACC1, which suggests that this miRNA may be a promising therapeutic target for the treatment of patients with such an aggressive gynecological cancer.
此前，已有多项研究报道多种微小RNA（miRNA）在宫颈癌中表达失调，且失调的miRNA可能在宫颈癌的发生发展过程中发挥关键作用。因此，研究在宫颈癌中异常表达的miRNA的具体作用及其潜在分子机制，对于早期诊断和有效的治疗方法至关重要。研究发现，miRNA - 877（miR - 877）在肝癌和肾细胞癌中表达下调，发挥肿瘤抑制性miRNA的作用。然而，miR - 877如何影响宫颈癌进展及其潜在分子机制仍有待阐明。在本研究中，采用逆转录定量PCR检测宫颈癌组织和细胞系中miR - 877的表达。使用MTT和Transwell细胞侵袭实验评估miR - 877过表达对宫颈癌细胞增殖和侵袭的影响。在本研究中，miR - 877在宫颈癌组织和细胞系中显著下调，且miR - 877表达水平的降低与宫颈癌患者国际妇产科联盟分期增加以及淋巴结转移增加显著相关。使用miR - 877模拟物上调miR - 877可导致宫颈癌细胞增殖和侵袭减少。通过生物信息学分析评估结肠癌转移相关蛋白1（MACC1），以确定其是否可能是miR - 877的潜在靶基因，并使用荧光素酶报告基因实验进行验证。此外，MACC1在宫颈癌组织中明显上调，其水平与miR - 877水平呈负相关。miR - 877过表达导致宫颈癌细胞中MACC1的mRNA和蛋白水平均降低。此外，敲低MACC1的功能效应与上调miR - 877在宫颈癌细胞中诱导的效应相似。MACC1恢复了miR - 877过表达介导的对宫颈癌细胞增殖和侵袭的抑制作用。总之，miR - 877可能通过直接靶向MACC1在宫颈癌中发挥抗肿瘤作用，这表明该miRNA可能是治疗这种侵袭性妇科癌症患者的一个有前景的治疗靶点。
