The role of HPV gene expression and selected cellular MiRNAs in lung cancer development,Microbial Pathogenesis

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The role of HPV gene expression and selected cellular MiRNAs in lung cancer development
Microbial Pathogenesis ( IF 3.8 ) Pub Date : 2020-12-07 , DOI: 10.1016/j.micpath.2020.104692
Bashdar Mahmud Hussen ₁ , Gelavizh Ahmadi ₂ , Havva Marzban ₃ , Maryam Ebadi Fard Azar ₄ , Saba Sorayyayi ₅ , Romina Karampour ₆ , Javid Sadri Nahand ₇ , Hazha Jamal Hidayat ₈ , Mohsen Moghoofei ₉

Affiliation

Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Department of Biotechnology, Faculty of Sciences, University of Maragheh, Maragheh, Iran.
Department of Pathology and Experimental Animals, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.
Student Research Committee, Iran University of Medical Sciences, Tehran, Iran.
Department of Clinical Biochemistry, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
Department of Pathobiology, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran.
Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Biology, College of Education, Salahaddin University, Erbil, Iraq.
Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

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.

中文翻译：

HPV基因表达和选定的细胞MiRNA在肺癌发展中的作用

背景

肺癌的高死亡率可以证明，迫切需要探索肿瘤生物学的新方面。人乳头瘤病毒（HPV）已被检测为肺癌发生的危险因素。这项研究的目的是确定HPV和细胞/ miRNA基因表达在上皮-间质转化（EMT）和肺癌发展中的作用。

方法

在该病例对照研究中，包括109个肺癌组织和52个对照。我们分析了HPV感染的存在，其基因型（在阳性样品中）和病毒基因（E2，E6和E7）的表达。此外，我们检查了细胞因子的表达，包括（a）p53和成视网膜细胞瘤（Rb）（作为抗癌基因），（b）EMT相关基因，（c）选定的miRNA。

结果

我们的结果报告了肿瘤组织和对照组织样品中HPV基因组的51.4％和23.1％。HPV阳性状态与肺癌之间存在显着相关性（OR = 3.26，95％CI = 1.47–7.02，P = 0.001）。HPV 16型是组织中最普遍的基因型。与HPV阴性组织相比，HPV阳性肿瘤/对照组织中p53，RB，TIMP1，CCNG-1，E-cad和PTPN13的表达降低，而MMP-2和N-cad的表达升高。此外，与HPV阴性组织相比，在miRNA中，在HPV阳性组织中let-7，miR-23，miR-34，miR-125，miR-146被下调，而miR-20，miR-424被上调。