Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Hong, Gu, Lingling, Zhang, Min, Chen, Huifen, Liao, Hong, Cao, Xueping, Yu, Lu, Zhang, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
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
_version_ 1784802359630626816
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
work_keys_str_mv AT chenhong interactionofmir200a3pwithyapregulatescellproliferationandmetastasisdifferentiallyinhpvpositiveandhpvnegativecervicalcancercells
AT gulingling interactionofmir200a3pwithyapregulatescellproliferationandmetastasisdifferentiallyinhpvpositiveandhpvnegativecervicalcancercells
AT zhangmin interactionofmir200a3pwithyapregulatescellproliferationandmetastasisdifferentiallyinhpvpositiveandhpvnegativecervicalcancercells
AT chenhuifen interactionofmir200a3pwithyapregulatescellproliferationandmetastasisdifferentiallyinhpvpositiveandhpvnegativecervicalcancercells
AT liaohong interactionofmir200a3pwithyapregulatescellproliferationandmetastasisdifferentiallyinhpvpositiveandhpvnegativecervicalcancercells
AT caoxueping interactionofmir200a3pwithyapregulatescellproliferationandmetastasisdifferentiallyinhpvpositiveandhpvnegativecervicalcancercells
AT yulu interactionofmir200a3pwithyapregulatescellproliferationandmetastasisdifferentiallyinhpvpositiveandhpvnegativecervicalcancercells
AT zhangjun interactionofmir200a3pwithyapregulatescellproliferationandmetastasisdifferentiallyinhpvpositiveandhpvnegativecervicalcancercells