Hsa-miR-194-5p and hsa-miR-195-5p are down-regulated expressed in high dysplasia HPV-positive Pap smear samples compared to normal cytology HPV-positive Pap smear samples

Abstract Background The human papillomavirus (HPV) infection may affect the miRNA expression pattern during cervical cancer (CC) development. To demonstrate the association between high-risk HPVs and the development of cervix dysplasia, we examined the expression patterns of hsa-miR-194-5p and hsa-m...

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Main Authors: Ali Dehghani, Fardin Khajepour, Mohammad Dehghani, Ehsan Razmara, Mohammadreza Zangouey, Maryam Fekri Soofi Abadi, Reza Bahram Abadi Nezhad, Shahriar Dabiri, Masoud Garshasbi
Format: Article
Language:English
Published: BMC 2024-02-01
Series:BMC Infectious Diseases
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Online Access:https://doi.org/10.1186/s12879-023-08942-1
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author Ali Dehghani
Fardin Khajepour
Mohammad Dehghani
Ehsan Razmara
Mohammadreza Zangouey
Maryam Fekri Soofi Abadi
Reza Bahram Abadi Nezhad
Shahriar Dabiri
Masoud Garshasbi
author_facet Ali Dehghani
Fardin Khajepour
Mohammad Dehghani
Ehsan Razmara
Mohammadreza Zangouey
Maryam Fekri Soofi Abadi
Reza Bahram Abadi Nezhad
Shahriar Dabiri
Masoud Garshasbi
author_sort Ali Dehghani
collection DOAJ
description Abstract Background The human papillomavirus (HPV) infection may affect the miRNA expression pattern during cervical cancer (CC) development. To demonstrate the association between high-risk HPVs and the development of cervix dysplasia, we examined the expression patterns of hsa-miR-194-5p and hsa-miR-195-5p in Pap smear samples from southeast Iranian women. We compared samples that were HPV-positive but showed no abnormality in the cytological examination to samples that were HPV-positive and had severe dysplasia. Methods Pap smear samples were obtained from 60 HPV-positive (HPV-16/18) patients with histologically confirmed severe dysplasia (cervical intra-epithelial neoplasia (CIN 3) or carcinoma in situ) and the normal cytology group. The expression of hsa-miR-194-5p and hsa-miR-195-5p was analyzed by real-time quantitative PCR, using specific stem-loop primers and U6 snRNA as the internal reference gene. Clinicopathological features were associated with miRNA expression levels. Furthermore, functional enrichment analysis was conducted using in silico tools. The Kaplan–Meier survival method was also obtained to discriminate survival-significant candidate miRNAs in CC, and receiver operating characteristic (ROC) curves were constructed to assess the diagnostic value. Results Compared to HPV-positive cytologically normal Pap smear samples, hsa-miR-194-5p and hsa-miR-195-5p relative expression decreased significantly in HPV-positive patients with a severe dysplasia Pap smear. Kaplan–Meier analysis indicated a significant association between the miR-194 decrease and poor CC survival. In essence, ROC curve analysis showed that miR-194-5p and miR-195-5p could serve as valuable markers for the development of cervix dysplasia in individuals who are positive for high-risk HPVs. Conclusions This study revealed that hsa-miR-194-5p and hsa-miR-195-5p may possess tumor suppressor capabilities in the context of cervical dysplasia progression. However, it remains uncertain whether these microRNAs are implicated in the transition of patients with high dysplasia to cervical cancer. We also showed the potential capability of candidate miRNAs as novel diagnostic biomarkers related to cervical dysplasia progression.
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spelling doaj.art-a9d5f9d5efbc41ef9d4694b45a3f2ede2024-03-05T17:48:43ZengBMCBMC Infectious Diseases1471-23342024-02-0124111310.1186/s12879-023-08942-1Hsa-miR-194-5p and hsa-miR-195-5p are down-regulated expressed in high dysplasia HPV-positive Pap smear samples compared to normal cytology HPV-positive Pap smear samplesAli Dehghani0Fardin Khajepour1Mohammad Dehghani2Ehsan Razmara3Mohammadreza Zangouey4Maryam Fekri Soofi Abadi5Reza Bahram Abadi Nezhad6Shahriar Dabiri7Masoud Garshasbi8Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares UniversityDepartment of Immunology, Afzalipour Faculty of Medicine, Kerman University of Medical SciencesPathology and Stem Cell Research Center, Kerman University of Medical SciencesAustralian Regenerative Medicine Institute, Monash UniversityPathology and Stem Cell Research Center, Kerman University of Medical SciencesPathology and Stem Cell Research Center, Kerman University of Medical SciencesDepartment of Microbiology, School of Medicine, Rafsanjan University of Medical SciencesPathology and Stem Cell Research Center, Kerman University of Medical SciencesDepartment of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares UniversityAbstract Background The human papillomavirus (HPV) infection may affect the miRNA expression pattern during cervical cancer (CC) development. To demonstrate the association between high-risk HPVs and the development of cervix dysplasia, we examined the expression patterns of hsa-miR-194-5p and hsa-miR-195-5p in Pap smear samples from southeast Iranian women. We compared samples that were HPV-positive but showed no abnormality in the cytological examination to samples that were HPV-positive and had severe dysplasia. Methods Pap smear samples were obtained from 60 HPV-positive (HPV-16/18) patients with histologically confirmed severe dysplasia (cervical intra-epithelial neoplasia (CIN 3) or carcinoma in situ) and the normal cytology group. The expression of hsa-miR-194-5p and hsa-miR-195-5p was analyzed by real-time quantitative PCR, using specific stem-loop primers and U6 snRNA as the internal reference gene. Clinicopathological features were associated with miRNA expression levels. Furthermore, functional enrichment analysis was conducted using in silico tools. The Kaplan–Meier survival method was also obtained to discriminate survival-significant candidate miRNAs in CC, and receiver operating characteristic (ROC) curves were constructed to assess the diagnostic value. Results Compared to HPV-positive cytologically normal Pap smear samples, hsa-miR-194-5p and hsa-miR-195-5p relative expression decreased significantly in HPV-positive patients with a severe dysplasia Pap smear. Kaplan–Meier analysis indicated a significant association between the miR-194 decrease and poor CC survival. In essence, ROC curve analysis showed that miR-194-5p and miR-195-5p could serve as valuable markers for the development of cervix dysplasia in individuals who are positive for high-risk HPVs. Conclusions This study revealed that hsa-miR-194-5p and hsa-miR-195-5p may possess tumor suppressor capabilities in the context of cervical dysplasia progression. However, it remains uncertain whether these microRNAs are implicated in the transition of patients with high dysplasia to cervical cancer. We also showed the potential capability of candidate miRNAs as novel diagnostic biomarkers related to cervical dysplasia progression.https://doi.org/10.1186/s12879-023-08942-1Cervical cancerCervical dysplasiaHuman papillomavirusHsa-miR-194-5pHsa-miR-195-5p
spellingShingle Ali Dehghani
Fardin Khajepour
Mohammad Dehghani
Ehsan Razmara
Mohammadreza Zangouey
Maryam Fekri Soofi Abadi
Reza Bahram Abadi Nezhad
Shahriar Dabiri
Masoud Garshasbi
Hsa-miR-194-5p and hsa-miR-195-5p are down-regulated expressed in high dysplasia HPV-positive Pap smear samples compared to normal cytology HPV-positive Pap smear samples
BMC Infectious Diseases
Cervical cancer
Cervical dysplasia
Human papillomavirus
Hsa-miR-194-5p
Hsa-miR-195-5p
title Hsa-miR-194-5p and hsa-miR-195-5p are down-regulated expressed in high dysplasia HPV-positive Pap smear samples compared to normal cytology HPV-positive Pap smear samples
title_full Hsa-miR-194-5p and hsa-miR-195-5p are down-regulated expressed in high dysplasia HPV-positive Pap smear samples compared to normal cytology HPV-positive Pap smear samples
title_fullStr Hsa-miR-194-5p and hsa-miR-195-5p are down-regulated expressed in high dysplasia HPV-positive Pap smear samples compared to normal cytology HPV-positive Pap smear samples
title_full_unstemmed Hsa-miR-194-5p and hsa-miR-195-5p are down-regulated expressed in high dysplasia HPV-positive Pap smear samples compared to normal cytology HPV-positive Pap smear samples
title_short Hsa-miR-194-5p and hsa-miR-195-5p are down-regulated expressed in high dysplasia HPV-positive Pap smear samples compared to normal cytology HPV-positive Pap smear samples
title_sort hsa mir 194 5p and hsa mir 195 5p are down regulated expressed in high dysplasia hpv positive pap smear samples compared to normal cytology hpv positive pap smear samples
topic Cervical cancer
Cervical dysplasia
Human papillomavirus
Hsa-miR-194-5p
Hsa-miR-195-5p
url https://doi.org/10.1186/s12879-023-08942-1
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