HPV 基因表达和选定的细胞 miRNAs 在肺癌发展中的作用。

The role of HPV gene expression and selected cellular MiRNAs in lung cancer development.

机构信息

Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Iraq.

Department of Biotechnology, Faculty of Sciences, University of Maragheh, Maragheh, Iran.

出版信息

Microb Pathog. 2021 Jan;150:104692. doi: 10.1016/j.micpath.2020.104692. Epub 2020 Dec 7.

DOI:10.1016/j.micpath.2020.104692

PMID:33301856

Abstract

BACKGROUND

The high mortality rate of lung cancer can be justified that strong need to explore new aspect of tumor biology. Human papillomavirus (HPV) has been detected as risk factor for the development of lung cancer. The aim of this study was to determine the role of HPV and cellular/miRNAs genes expression in the epithelial-mesenchymal transition (EMT) and development of lung cancer.

METHODS

In this case-control study, 109 lung cancer tissue and 52 controls were included. We analyzed the presence of HPV infection, its genotypes (in positive samples) and the expression of viral genes (E2, E6 and E7). Also, We examined the expression of celluar factors including (a) p53 and retinoblastoma (Rb) (as anti-carcinogenic genes), (b) EMT related genes, (c) selected miRNAs.

RESULTS

Our results reported 51.4% and 23.1% of HPV genome in tumor tissues and control tissues samples, respectively. There was a significant association between the HPV positive status and lung cancer (OR = 3.26, 95% C.I = 1.47-7.02, P = 0.001). HPV type 16 was the most prevalent genotype in tissues. The expression of p53, RB, TIMP1, CCNG-1, E-cad and PTPN13 were decreased while MMP-2 and N-cad were increased in HPV-positive tumor/control tissues compared to HPV-negative tissues. Also, among miRNAs, let-7, miR-23, miR-34, miR-125, miR-146 were downregulated and miR-20, miR-424 were upregulated in HPV-positve tissues compared to HPV-negative tissues.

CONCLUSION

This study demonstrated that HPV infection and interaction with cellular genes and miRNAs promote EMT which involved in the lung cancer development.

摘要

背景

肺癌的高死亡率使得人们强烈需要探索肿瘤生物学的新方面。人乳头瘤病毒（HPV）已被确定为肺癌发展的危险因素。本研究旨在确定 HPV 及其细胞/miRNA 基因表达在上皮-间充质转化（EMT）和肺癌发展中的作用。

方法

在这项病例对照研究中，纳入了 109 例肺癌组织和 52 例对照。我们分析了 HPV 感染的存在、其基因型（在阳性样本中）以及病毒基因（E2、E6 和 E7）的表达。此外，我们还检测了细胞因子的表达，包括（a）p53 和视网膜母细胞瘤（Rb）（作为抗癌基因）、（b）EMT 相关基因、（c）选定的 miRNAs。

结果

我们的结果报告了肿瘤组织和对照组织样本中 HPV 基因组的 51.4%和 23.1%。HPV 阳性状态与肺癌之间存在显著相关性（OR=3.26，95%CI=1.47-7.02，P=0.001）。组织中最常见的 HPV 基因型是 16 型。与 HPV 阴性组织相比，HPV 阳性肿瘤/对照组织中 p53、RB、TIMP1、CCNG-1、E-钙粘蛋白和 PTPN13 的表达降低，而 MMP-2 和 N-钙粘蛋白的表达增加。此外，在 miRNA 中，与 HPV 阴性组织相比，HPV 阳性组织中 let-7、miR-23、miR-34、miR-125、miR-146 下调，miR-20、miR-424 上调。