MiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A

Abstract Background Ovarian cancer (OC), a kind of gynecological cancer, is characterized by high mortality rate, with microRNAs (miRNAs) playing essential roles in it. However, the clinical significance of miRNAs and their molecular mechanisms in OC are mostly unknown. Methods miR-149-3p expression...

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Autores principales:	Jin Wang, Lingxia Liu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Ovarian cancer miR-149-3p CDKN1A TIMP2 Cisplatin resistance Gynecology and obstetrics RG1-991
Acceso en línea:	https://doaj.org/article/de6c07e122ab48a48375558e7e8b949a
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spelling	oai:doaj.org-article:de6c07e122ab48a48375558e7e8b949a2021-11-21T12:32:06ZMiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A10.1186/s13048-021-00919-51757-2215https://doaj.org/article/de6c07e122ab48a48375558e7e8b949a2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13048-021-00919-5https://doaj.org/toc/1757-2215Abstract Background Ovarian cancer (OC), a kind of gynecological cancer, is characterized by high mortality rate, with microRNAs (miRNAs) playing essential roles in it. However, the clinical significance of miRNAs and their molecular mechanisms in OC are mostly unknown. Methods miR-149-3p expression was predicted through Gene Expression Omnibus (GEO) data in OC and confirmed by q-PCR in various OC cells and tissues from patients with different clinical characteristics. Moreover, its roles in terms of proliferation, migration and invasion were measured by CCK-8, colony formation, wound healing and transwell assays in OC cells including cisplatin-resistant and cisplatin-sensitive cells. And its effect on epithelial-mesenchymal transition was also assessed through detecting related protein expression. Additionally, its potential targets were verified by dual luciferase assay and Ago-RIP assay. Finally, its oncogenic functions were explored in vivo. Results In data from GSE79943, GSE131790, and TCGA, miR-149-3p was found to be highly expressed in OC tissues and associated with poor survival. In metastasis and chemoresistant tissues and cisplatin-resistant OC cells, its high expression was confirmed. In terms of tumorigenic effects, miR-149-3p knockdown in cisplatin-resistant OC cells inhibited its cisplatin resistance and other malignant phenotypes, while miR-149-3p overexpression in cisplatin-resistant OC cells led to contrary results. Mechanistically, miR-149-3p targeted 3’UTR of CDKN1A and TIMP2 to function as an oncogenic miRNA. Conclusion In brief, miR-149-3p promoted cisplatin resistance and EMT in OC by downregulating CDKN1A and TIMP2, which might provide a potential therapeutic target for OC treatment.Jin WangLingxia LiuBMCarticleOvarian cancermiR-149-3pCDKN1ATIMP2Cisplatin resistanceGynecology and obstetricsRG1-991ENJournal of Ovarian Research, Vol 14, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ovarian cancer miR-149-3p CDKN1A TIMP2 Cisplatin resistance Gynecology and obstetrics RG1-991
spellingShingle	Ovarian cancer miR-149-3p CDKN1A TIMP2 Cisplatin resistance Gynecology and obstetrics RG1-991 Jin Wang Lingxia Liu MiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A
description	Abstract Background Ovarian cancer (OC), a kind of gynecological cancer, is characterized by high mortality rate, with microRNAs (miRNAs) playing essential roles in it. However, the clinical significance of miRNAs and their molecular mechanisms in OC are mostly unknown. Methods miR-149-3p expression was predicted through Gene Expression Omnibus (GEO) data in OC and confirmed by q-PCR in various OC cells and tissues from patients with different clinical characteristics. Moreover, its roles in terms of proliferation, migration and invasion were measured by CCK-8, colony formation, wound healing and transwell assays in OC cells including cisplatin-resistant and cisplatin-sensitive cells. And its effect on epithelial-mesenchymal transition was also assessed through detecting related protein expression. Additionally, its potential targets were verified by dual luciferase assay and Ago-RIP assay. Finally, its oncogenic functions were explored in vivo. Results In data from GSE79943, GSE131790, and TCGA, miR-149-3p was found to be highly expressed in OC tissues and associated with poor survival. In metastasis and chemoresistant tissues and cisplatin-resistant OC cells, its high expression was confirmed. In terms of tumorigenic effects, miR-149-3p knockdown in cisplatin-resistant OC cells inhibited its cisplatin resistance and other malignant phenotypes, while miR-149-3p overexpression in cisplatin-resistant OC cells led to contrary results. Mechanistically, miR-149-3p targeted 3’UTR of CDKN1A and TIMP2 to function as an oncogenic miRNA. Conclusion In brief, miR-149-3p promoted cisplatin resistance and EMT in OC by downregulating CDKN1A and TIMP2, which might provide a potential therapeutic target for OC treatment.
format	article
author	Jin Wang Lingxia Liu
author_facet	Jin Wang Lingxia Liu
author_sort	Jin Wang
title	MiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A
title_short	MiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A
title_full	MiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A
title_fullStr	MiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A
title_full_unstemmed	MiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A
title_sort	mir-149-3p promotes the cisplatin resistance and emt in ovarian cancer through downregulating timp2 and cdkn1a
publisher	BMC
publishDate	2021
url	https://doaj.org/article/de6c07e122ab48a48375558e7e8b949a
work_keys_str_mv	AT jinwang mir1493ppromotesthecisplatinresistanceandemtinovariancancerthroughdownregulatingtimp2andcdkn1a AT lingxialiu mir1493ppromotesthecisplatinresistanceandemtinovariancancerthroughdownregulatingtimp2andcdkn1a
_version_	1718418976479903744

MiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A

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