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Interaction of miR-200a-3p with YAP regulates cell proliferation and metastasis differentially in HPV-positive and HPV-negative cervical cancer cells
BACKGROUND: Although evidence has revealed that miR-200a-3p is involved in the malignant progression of various tumors, the regulatory mechanism of miR-200a-3p in the development of cervical cancer (CC) cells with different HPV statuses remains unknown. The present study was to investigate the diffe...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533500/ https://www.ncbi.nlm.nih.gov/pubmed/36195847 http://dx.doi.org/10.1186/s12885-022-10118-0 |
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author | Chen, Hong Gu, Lingling Zhang, Min Chen, Huifen Liao, Hong Cao, Xueping Yu, Lu Zhang, Jun |
author_facet | Chen, Hong Gu, Lingling Zhang, Min Chen, Huifen Liao, Hong Cao, Xueping Yu, Lu Zhang, Jun |
author_sort | Chen, Hong |
collection | PubMed |
description | BACKGROUND: Although evidence has revealed that miR-200a-3p is involved in the malignant progression of various tumors, the regulatory mechanism of miR-200a-3p in the development of cervical cancer (CC) cells with different HPV statuses remains unknown. The present study was to investigate the differential effects of either miR-200a-3p or YAP on tumorous cells’ fate in vitro in HPV-negative and HPV-positive cervical cancer cell models, and to explore if the changes in proliferation, migration, and invasion of the CC cells with different HPV statuses could be attributed to the differential interactions between miR-200a-3p and YAP. METHODS: The colony formation assays, EDU assays and Transwell assays were performed for CC cell proliferation, migration and invasion capacities analysis. The prediction of downstream targets of miR-200a-3p was performed by bioinformatical databases. The dual-luciferase reporter assays were used to validate the binding sites of miR-200a-3p and YAP. The qRT-PCR assays were performed to quantify the mRNA expression of miR-200a-3p and YAP, and the protein levels of YAP were examined by Western blot analysis. RESULTS: The results demonstrated that miR-200a-3p overexpression suppressed proliferation, migration, and invasion of the HPV-negative C33A cells but promoted the growth and metastasis of HPV-positive CC cells, while YAP promoted the cell growth and metastasis not only in HPV-negative but also in the HPV-positive CC cells. The suppressive role of miR-200a-3p in C33A cells appeared to be mediated partially by direct interaction with YAP, and YAP might participate in miR-200a-3p-mediated cellular changes in CC cells differing from not only the presence or absence of HPV but even also the subtypes of HPV of CC cells. Meanwhile, we preliminarily revealed that the expression level of miR-200a-3p was significantly decreased in HPV-negative, but not in HPV16-positive cervical neoplasm mucus samples. CONCLUSION: miR-200a-3p-mediated functional changes of YAP exhibited regulatory effects on cells’ fate differentially in HPV-negative and HPV-positive cervical cancer cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-10118-0. |
format | Online Article Text |
id | pubmed-9533500 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-95335002022-10-06 Interaction of miR-200a-3p with YAP regulates cell proliferation and metastasis differentially in HPV-positive and HPV-negative cervical cancer cells Chen, Hong Gu, Lingling Zhang, Min Chen, Huifen Liao, Hong Cao, Xueping Yu, Lu Zhang, Jun BMC Cancer Research BACKGROUND: Although evidence has revealed that miR-200a-3p is involved in the malignant progression of various tumors, the regulatory mechanism of miR-200a-3p in the development of cervical cancer (CC) cells with different HPV statuses remains unknown. The present study was to investigate the differential effects of either miR-200a-3p or YAP on tumorous cells’ fate in vitro in HPV-negative and HPV-positive cervical cancer cell models, and to explore if the changes in proliferation, migration, and invasion of the CC cells with different HPV statuses could be attributed to the differential interactions between miR-200a-3p and YAP. METHODS: The colony formation assays, EDU assays and Transwell assays were performed for CC cell proliferation, migration and invasion capacities analysis. The prediction of downstream targets of miR-200a-3p was performed by bioinformatical databases. The dual-luciferase reporter assays were used to validate the binding sites of miR-200a-3p and YAP. The qRT-PCR assays were performed to quantify the mRNA expression of miR-200a-3p and YAP, and the protein levels of YAP were examined by Western blot analysis. RESULTS: The results demonstrated that miR-200a-3p overexpression suppressed proliferation, migration, and invasion of the HPV-negative C33A cells but promoted the growth and metastasis of HPV-positive CC cells, while YAP promoted the cell growth and metastasis not only in HPV-negative but also in the HPV-positive CC cells. The suppressive role of miR-200a-3p in C33A cells appeared to be mediated partially by direct interaction with YAP, and YAP might participate in miR-200a-3p-mediated cellular changes in CC cells differing from not only the presence or absence of HPV but even also the subtypes of HPV of CC cells. Meanwhile, we preliminarily revealed that the expression level of miR-200a-3p was significantly decreased in HPV-negative, but not in HPV16-positive cervical neoplasm mucus samples. CONCLUSION: miR-200a-3p-mediated functional changes of YAP exhibited regulatory effects on cells’ fate differentially in HPV-negative and HPV-positive cervical cancer cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-10118-0. BioMed Central 2022-10-04 /pmc/articles/PMC9533500/ /pubmed/36195847 http://dx.doi.org/10.1186/s12885-022-10118-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Chen, Hong Gu, Lingling Zhang, Min Chen, Huifen Liao, Hong Cao, Xueping Yu, Lu Zhang, Jun Interaction of miR-200a-3p with YAP regulates cell proliferation and metastasis differentially in HPV-positive and HPV-negative cervical cancer cells |
title | Interaction of miR-200a-3p with YAP regulates cell proliferation and metastasis differentially in HPV-positive and HPV-negative cervical cancer cells |
title_full | Interaction of miR-200a-3p with YAP regulates cell proliferation and metastasis differentially in HPV-positive and HPV-negative cervical cancer cells |
title_fullStr | Interaction of miR-200a-3p with YAP regulates cell proliferation and metastasis differentially in HPV-positive and HPV-negative cervical cancer cells |
title_full_unstemmed | Interaction of miR-200a-3p with YAP regulates cell proliferation and metastasis differentially in HPV-positive and HPV-negative cervical cancer cells |
title_short | Interaction of miR-200a-3p with YAP regulates cell proliferation and metastasis differentially in HPV-positive and HPV-negative cervical cancer cells |
title_sort | interaction of mir-200a-3p with yap regulates cell proliferation and metastasis differentially in hpv-positive and hpv-negative cervical cancer cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533500/ https://www.ncbi.nlm.nih.gov/pubmed/36195847 http://dx.doi.org/10.1186/s12885-022-10118-0 |
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