HPV16+-miRNAs in cervical cancer and the anti-tumor role played by miR-5701
HPV16+-miRNAs in cervical cancer and the anti-tumor role played by miR-5701
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DOI：
10.1002/jgm.3126
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发表时间：
2019-10-25
影响因子：
3.5
通讯作者：
Yang, Jie
中科院分区：
文献类型：
--
作者：
Pulati, Nuerbieke;Zhang, Zegao;Yang, Jie
背景宫颈癌早期诊断困难，预后不佳。本研究旨在探讨新疆维吾尔族宫颈癌患者血清中HPV 16相关microRNA（miRNAs）的表达情况，并对差异表达的miRNAs进行分析。方法收集30例HPV 16阳性患者（HPV 16 Pos）和30例HPV 16阴性患者（HPV 16 Neg）的血清，通过功能和途径富集分析筛选差异表达的miRNAs。接下来，培养宫颈癌细胞。将miR-5701模拟物和抑制剂转染到细胞中。通过定量逆转录-聚合酶链反应检测miR-5701的水平。使用细胞计数试剂盒-8测定法检测细胞的增殖。Western blotting检测THBS 4的表达。结果在HPV 16阴性组中，发现3种上调的miRNAs（hsa-miR-1291、hsa-miR-144- 5 p和hsa-miR-5701）和7种下调的已知miRNAs（hsa-miR-21- 5 p、hsa-miR-101- 3 p、hsa-miR-370- 3 p、hsa-miR-151 a-3 p、hsa-miR-144- 3 p、hsa-miR-199 a-3 p和hsa-miR-199 b-3 p）。丝裂原活化蛋白激酶信号通路被认为是HPV 16相关宫颈癌发生的重要机制。此外，miR-5701还能抑制宫颈癌细胞的增殖，并抑制THBS 4的表达（P < 0.05），证实THBS 4是miR-5701的靶基因。结论在本研究中，我们确定了10个差异表达的miRNAs，可能是潜在的标志物或宫颈癌的治疗靶点。miR-5701抑制宫颈癌细胞增殖及其靶基因THBS 4的表达
Background The early diagnosis of cervical cancer is difficult, resulting in an unsatisfactory prognosis. The present study aimed to explore the expression of HPV16-related microRNAs (miRNAs) in the serum of Uygur cervical cancer in Sinkiang and analyze the miRNAs showing different expression. Methods The serum of 30 HPV16 positive (HPV16Pos) and 30 negative patients (HPV16Neg) was collected and then the differentially expressed miRNAs were screened out by function and pathway enrichment analyses. Next, the cervical cancer cells were cultured. miR-5701-mimic and inhibitor were transfected into cells. The level of miR-5701 was detected by a quantitative reverse transcriptase-polymerase chain reaction. The proliferation of cells was detected using a Cell Counting Kit-8 assay. Western blotting was used to measure the expression of THBS4. Results We identified three up-regulated miRNAs (hsa-miR-1291, hsa-miR-144-5p and hsa-miR-5701) and seven down-regulated known-miRNAs (hsa-miR-21-5p, hsa-miR-101-3p, hsa-miR-370-3p, hsa-miR-151a-3p, hsa-miR-144-3p, hsa-miR-199a-3p and hsa-miR-199b-3p) relative to HPV16Neg. The mitogen-activated protein kinase signal pathway is predicted to be a key mechanism of HPV16-related cervical cancer. Furthermore, miR-5701 inhibits the proliferation of cervical cancer cells and suppresses the expression of THBS4 (P < 0.05), which was confirmed as a target gene of miR-5701. Conclusions In the present study, we confirm 10 differentially expressed miRNAs that could be potential markers or therapeutic targets of cervical cancer. miR-5701 inhibits the proliferation of cervical cancer cells and the expression of its target gene THBS4.