Abstract

The study aimed to investigate the state of human papillomavirus (HPV) infection in patients with cervical cancer in the Uyghur population in China and to identify miRNA as biomarker for cervical cancer and HPV infection. We also performed genotyping to determine the variation in the types of HPV. Using microRNA (miRNA) microarray technology, differential miRNA expression between HPV-infected cervical cancer and uninfected normal cervical tissues was determined; the microarray results were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) using 20 samples of both the tissues. The infection rate of HPV in patients with cervical cancer was 96.7% (29 of 30), and the main subtype identified was HPV16 (29 of 29). HPV16 integration assay demonstrated that the majority of infectious cases were of the integrated form (26 of 29). Analysis of 140 miRNAs demonstrated greater than two-fold change in miRNA expression in HPV-infected cervical cancer tissue as compared to that in uninfected cervical tissue. The qRT-PCR analysis verified that the expression of miR-15a-5p, miR-17-5p, miR-20a-5p, miR-21-5p, miR-96, miR-106b-5p, and miR-3653 was higher, while the expression of miR-497-5p was lower in cancer tissues than in normal tissues. The results demonstrate significant changes in miRNA expression in cervical cancer tissues associated with HPV infection as compared to that in normal tissues. These molecular markers may be useful for an early diagnosis and prognosis of cervical cancer in specific human populations.

Highlights

  • Thirty cervical tissues were used to detect human papillomavirus (HPV) infection—six cervical cancer tissues and six normal cervical tissues were used in miRNA microarray, and twenty cervical cancer tissues and twenty normal cervical tissues were used for validation of qPCR

  • The samples used for miRNA microarrays were from six cervical cancer tissues infected with HPV16 and six uninfected normal cervical tissues

  • For quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) experiments, 20 cervical cancer tissues infected with HPV16 and 20 uninfected normal cervical tissues were analyzed

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Summary

Introduction

XJDX0208-2013-03) and General Program, Natural Science Foundation of Xinjiang Cervical cancer is prevalent worldwide and is often fatal [1]. The factors leading to its occurrence are not fully understood, human papillomavirus (HPV) infection, as a causative agent of cervical cancer, has been well documented [2,3,4]. There are several subtypes of HPV, and those that cause cancers are generally referred as high-risk HPV (hrHPV). There are more than 20 common subtypes of hrHPV, with HPV16 being the most prevalent [5]. A previous study has shown a high degree of association between the carcinogenicity of hrHPV and its PLOS ONE | DOI:10.1371/journal.pone.0164701. A previous study has shown a high degree of association between the carcinogenicity of hrHPV and its PLOS ONE | DOI:10.1371/journal.pone.0164701 October 20, 2016

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