The Second Hospital of Tianjin Medical University, 300070 Tianjin, China.
Department of Medical Microbiology, School of Basic Medical Sciences, Tianjin Medical University, 300070 Tianjin, China.
Sci Rep. 2016 Sep 12;6:33229. doi: 10.1038/srep33229.
Cervical cancer (CC) is a malignant solid tumor, which is one of the main causes of morbidity and mortality in women. Persistent High-risk human papillomavirus (hrHPV) infection is closely related to cervical cancer and autophagy has been suggested to inhibit viral infections. miRNAs have been reported to regulate autophagy in many solid tumors with many studies implicating miR-224-3p in the regulation of autophagy. In this study, we performed a miRNA microarray analysis on CC tissues and found that a large number of miRNAs with differential expressions in hrHPV-infected tissues. We identified miR-224-3p as a candidate miRNA selectively up regulated in HPV-infected tissues and cell lines. Further analysis revealed that miR-224-3p regulates autophagy in cervical cancer tissues and cell lines. While the overexpression of miR-224-3p inhibits autophagy in HPV-infected cells, knocking down endogenous miR-224-3p increases autophagy activity in the same cells. In addition, we found that miR-224-3p directly inhibits the expression of autophagy related gene, FAK family-interacting protein of 200 kDa (FIP200). In summary, we found that miR-224-3p regulates autophagy in hrHPV-induced cervical cancer cells through targeting FIP200 expression.
宫颈癌（CC）是一种恶性实体肿瘤，是女性发病率和死亡率的主要原因之一。持续性高危型人乳头瘤病毒（hrHPV）感染与宫颈癌密切相关，自噬已被证明能抑制病毒感染。已有研究表明，miRNAs 可调节许多实体肿瘤中的自噬，其中 miR-224-3p 已被报道参与自噬的调节。在本研究中，我们对 CC 组织进行了 miRNA 微阵列分析，发现大量在 hrHPV 感染组织中表达差异的 miRNAs。我们将 miR-224-3p 鉴定为 HPV 感染组织和细胞系中选择性上调的候选 miRNA。进一步分析表明，miR-224-3p 调节宫颈癌组织和细胞系中的自噬。miR-224-3p 的过表达抑制 HPV 感染细胞中的自噬，而内源性 miR-224-3p 的敲低则增加相同细胞中的自噬活性。此外，我们发现 miR-224-3p 可直接抑制自噬相关基因 FAK 家族相互作用蛋白 200kDa（FIP200）的表达。综上所述，我们发现 miR-224-3p 通过靶向 FIP200 表达调节 hrHPV 诱导的宫颈癌细胞中的自噬。
