Department of Gynecology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China.
Oncol Rep. 2017 Dec;38(6):3639-3649. doi: 10.3892/or.2017.6049. Epub 2017 Oct 20.
Cervical cancer is one of the most common female malignancies worldwide. Emerging data have shown that microRNAs (miRNAs) play significant roles in various human cancers, including cervical cancer. Aberrantly expressed miRNAs in cervical cancer contribute to tumour occurrence and development as either tumour suppressors or promoters. Research suggests that miRNA-433 (miR-433) possibly plays an important role in the development of various cancer types. However, no study has explored the expression patterns, roles and underlying mechanisms of miR-433 in cervical cancer. In the present study, we demonstrated significant downregulation of miR-433 in cervical cancer tissues and cell lines. Low miR-433 expression was found to significantly correlate with patient characteristics including tumour size, International Federation of Gynecology and Obstetrics stage, lymph node and distant metastases. Functional studies showed that restoration of miR-433 inhibited cell proliferation and invasion and increased apoptosis in cervical cancer cells. Metadherin (MTDH) was also validated as a direct target gene of miR-433. MTDH mRNA expression was upregulated in cervical cancer tissues and was inversely correlated with miR-433 expression. MTDH knockdown showed similar tumour-suppressive roles as miR-433 overexpression in regards to cervical cancer cell proliferation, invasion and apoptosis. Rescue experiments revealed that MTDH overexpression markedly reversed the effects of miR-433 overexpression in regards to proliferation, invasion and apoptosis of cervical cancer cells. Further investigations revealed that miR-433 inactivated AKT and β-catenin pathways in cervical cancer. Collectively, these findings indicate the essential roles of miR-433 in suppressing cervical cancer progression and suggest its potential as a therapeutic target for the treatment of cervical cancer.
宫颈癌是全球最常见的女性恶性肿瘤之一。新出现的数据表明，microRNAs（miRNAs）在包括宫颈癌在内的各种人类癌症中发挥着重要作用。宫颈癌中异常表达的 miRNAs 作为肿瘤抑制因子或促进因子，促进肿瘤的发生和发展。研究表明，miRNA-433（miR-433）可能在各种癌症类型的发展中发挥重要作用。然而，尚无研究探讨 miR-433 在宫颈癌中的表达模式、作用和潜在机制。在本研究中，我们证实 miR-433 在宫颈癌组织和细胞系中明显下调。低表达 miR-433 与患者特征显著相关，包括肿瘤大小、国际妇产科联合会分期、淋巴结和远处转移。功能研究表明，恢复 miR-433 可抑制宫颈癌细胞的增殖和侵袭，并增加细胞凋亡。黏附蛋白（MTDH）也被验证为 miR-433 的直接靶基因。MTDH mRNA 在宫颈癌组织中上调，与 miR-433 表达呈负相关。MTDH 敲低显示出与 miR-433 过表达类似的肿瘤抑制作用，可抑制宫颈癌细胞的增殖、侵袭和凋亡。挽救实验表明，MTDH 过表达可显著逆转 miR-433 过表达对宫颈癌细胞增殖、侵袭和凋亡的影响。进一步研究表明，miR-433 可使 AKT 和 β-catenin 通路失活。总之，这些发现表明 miR-433 在抑制宫颈癌进展中具有重要作用，并提示其作为宫颈癌治疗的潜在治疗靶点。
