Department of Gynecology and Obstetrics, Peking University People's Hospital, Beijing 10004, P.R. China.
Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing 100191, P.R. China.
Mol Med Rep. 2017 Oct;16(4):5464-5470. doi: 10.3892/mmr.2017.7231. Epub 2017 Aug 11.
Human papillomavirus (HPV) infection alone is not sufficient for development of cervical cancer and further risk factors are involved, however, the underlying mechanism remains to be elucidated. The authors previously used a microarray assay to reveal microR‑20b (miR‑20b) as a key node in the miRNA‑mRNA network of cervical carcinoma. The present study demonstrated an increased expression of miR‑20b in cervical carcinoma tissue. MiR‑20b was regulated by HPV E6 oncoprotein in cervical cancer. Furthermore, miR‑20b overexpression with mimics induced cell morphological alterations and the epithelial‑mesenchymal transition. Treating cervical cancer cells with the miR‑20b inhibitor decreased the migration and invasion of cervical cancer cells. Tissue inhibitor of metalloproteinase 2 (TIMP‑2), a possible antagonist of matrix metalloproteinase 2, is a metastasis suppressor and predicted to be a potential target of miR‑20b. Fluorescence signals were decreased on transducing HeLa cells with a TIMP‑2 3'‑untranslated region plasmid and miR‑20b mimics compared with control. Finally, TIMP‑2 was identified as a novel target of miR‑20b and was demonstrated to be regulated by the HPV oncoprotein. In addition, miR‑20b and TIMP‑2 were involved in cell invasion regulated by HPV E6. The present study demonstrated a novel pathway of HPV/miR‑20b/TIMP‑2 during the process of invasion in cervical cancer cells.
人乳头瘤病毒（HPV）感染本身不足以导致宫颈癌的发生，还涉及其他危险因素，但潜在的机制仍有待阐明。作者先前使用微阵列分析揭示了 microR-20b（miR-20b）作为宫颈癌 miRNA-mRNA 网络中的关键节点。本研究表明 miR-20b 在宫颈癌组织中表达增加。HPV E6 癌蛋白调节宫颈癌中的 miR-20b。此外，miR-20b 模拟物的过表达诱导细胞形态改变和上皮-间充质转化。用 miR-20b 抑制剂处理宫颈癌细胞可降低宫颈癌细胞的迁移和侵袭。组织金属蛋白酶抑制剂 2（TIMP-2）是基质金属蛋白酶 2 的可能拮抗剂，是一种转移抑制因子，预测是 miR-20b 的潜在靶标。与对照相比，转导 HeLa 细胞的 TIMP-2 3'-UTR 质粒和 miR-20b 模拟物的荧光信号减少。最后，鉴定出 TIMP-2 是 miR-20b 的一个新靶标，并且受 HPV 癌蛋白调节。此外，miR-20b 和 TIMP-2 参与 HPV E6 调节的细胞侵袭。本研究表明了 HPV/miR-20b/TIMP-2 在宫颈癌细胞侵袭过程中的新途径。
