人乳头瘤病毒（HPV）与前列腺癌（PCa）：HPV基因表达及特定细胞微小RNA在前列腺癌发生发展中的潜在作用

Human papilloma virus (HPV) and prostate cancer (PCa): The potential role of HPV gene expression and selected cellular MiRNAs in PCa development.

作者信息

Khatami Alireza, Nahand Javid Sadri, Kiani Seyed Jalal, Khoshmirsafa Majid, Moghoofei Mohsen, Khanaliha Khadijeh, Tavakoli Ahmad, Emtiazi Nikoo, Bokharaei-Salim Farah

机构信息

Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Microb Pathog. 2022 May;166:105503. doi: 10.1016/j.micpath.2022.105503. Epub 2022 Apr 7.

DOI:10.1016/j.micpath.2022.105503

PMID:35398468

Abstract

BACKGROUND

Prostate cancer (PCa) is one of the most common and health-threatening cancers in men worldwide. The human papillomavirus (HPV) is considered one of the organisms with the potential to be involved in the progression of this cancer. In the present study, we evaluated the association between the expression levels of HPV genes with the expression of selected cellular miRNAs (miR-19a, miR-21, miR-23b, miR-34a, miR-150-5p, and miR-155) and their targets genes (P53, Rb, c-Myc, TIMP-1, MMP-2, MMP-9, PDCD4, Bcl-2, and Survivin) in PCa tissue samples.

METHODS

HPV detection and genotyping were performed on the tissues of 112 PCa patients and 39 healthy individuals. The expression profile of miRNA was evaluated by SYBR Green-based real-time PCR. As well Human Survivin ELISA Kit was utilized to determine the concentrations of Retinoblastoma, P53, survivin, Bcl-2, c-Myc, TIMP-1, MMP-2, MMP-9, and PDCD4 in the prostate tissues.

RESULTS

According to our findings, HPV genome was detected in 28.7% (21/73) of PCa tissue specimens and 17.94% (7/39) control samples. There was no significant association between the presence of HPV infection with PCa (OR = 2.01, 95%CI = 0.8-5.68, P = 0.102). We found that mean expression level of miR-19a (3.7 ± 4.3, p-value: 0.0007), and -21 (2.5 ± 2.8, p-value<0.0001) were significantly higher and miR-23b (-2.14 ± 3.08, p-value: 0.003) and -34a (-3.12 ± 3.28, p-value: 0.0001) levels were significantly lower in PCa tissue samples than in control tissue samples.

CONCLUSION

Present research indicated that HPV positive PCa has a distinct miRNA profile compared with HPV negative PCa.

摘要

背景

前列腺癌（PCa）是全球男性中最常见且对健康构成威胁的癌症之一。人乳头瘤病毒（HPV）被认为是可能参与这种癌症进展的病原体之一。在本研究中，我们评估了HPV基因表达水平与前列腺癌组织样本中所选细胞微小RNA（miR-19a、miR-21、miR-23b、miR-34a、miR-150-5p和miR-155）及其靶基因（P53、Rb、c-Myc、TIMP-1、MMP-2、MMP-9、PDCD4、Bcl-2和Survivin）表达之间的关联。

方法

对112例前列腺癌患者和39名健康个体的组织进行HPV检测和基因分型。通过基于SYBR Green的实时PCR评估微小RNA的表达谱。同时使用人Survivin ELISA试剂盒测定前列腺组织中视网膜母细胞瘤、P53、Survivin、Bcl-2、c-Myc、TIMP-1、MMP-2、MMP-9和PDCD4的浓度。

结果

根据我们的研究结果，在28.7%（21/73）的前列腺癌组织标本和17.94%（7/39）的对照样本中检测到HPV基因组。HPV感染与前列腺癌之间无显著关联（OR = 2.01，95%CI = 0.8 - 5.68，P = 0.102）。我们发现，前列腺癌组织样本中miR-19a（3.7 ± 4.3，p值：0.0007）和miR-21（2.5 ± 2.8，p值<0.0001）的平均表达水平显著高于对照组织样本，而miR-23b（-2.14 ± 3.08，p值：0.003）和miR-34a（-3.12 ± 3.28，p值：0.0001）水平显著低于对照组织样本。