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Oncogenic Role of miR-200c-3p in High-Grade Serous Ovarian Cancer Progression via Targeting the 3′-Untranslated Region of DLC1

High-grade serous ovarian cancer (HGSC) is the most common ovarian cancer with highly metastatic properties. A small non-coding RNA, microRNA (miRNA) was discovered to be a major regulator in many types of cancers through binding at the 3′-untranslated region (3′UTR), leading to degradation of the m...

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Autores principales: Ankasha, Sheril June, Shafiee, Mohamad Nasir, Abdul Wahab, Norhazlina, Raja Ali, Raja Affendi, Mokhtar, Norfilza Mohd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198916/
https://www.ncbi.nlm.nih.gov/pubmed/34071861
http://dx.doi.org/10.3390/ijerph18115741
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author Ankasha, Sheril June
Shafiee, Mohamad Nasir
Abdul Wahab, Norhazlina
Raja Ali, Raja Affendi
Mokhtar, Norfilza Mohd
author_facet Ankasha, Sheril June
Shafiee, Mohamad Nasir
Abdul Wahab, Norhazlina
Raja Ali, Raja Affendi
Mokhtar, Norfilza Mohd
author_sort Ankasha, Sheril June
collection PubMed
description High-grade serous ovarian cancer (HGSC) is the most common ovarian cancer with highly metastatic properties. A small non-coding RNA, microRNA (miRNA) was discovered to be a major regulator in many types of cancers through binding at the 3′-untranslated region (3′UTR), leading to degradation of the mRNA. In this study, we sought to investigate the underlying mechanisms involved in the dysregulation of miR-200c-3p in HGSC progression and metastasis. We identified the upregulation of miR-200c-3p expression in different stages of HGSC clinical samples and the downregulation of the tumor suppressor gene, Deleted in Liver Cancer 1 (DLC1), expression. Over expression of miR-200c-3p in HGSC cell lines downregulated DLC1 but upregulated the epithelial marker, E-cadherin (CDH1). Based on in silico analysis, two putative binding sites were found within the 3′UTR of DLC1, and we confirmed the direct binding of miR-200c-3p to the target binding motif at position 1488–1495 bp of 3′UTR of DLC1 by luciferase reporter assay in a SKOV3 cell line co-transfected with vectors and miR-200c-3p mimic. These data showed that miR-200c-3p regulated the progression of HGSC by regulating DLC1 expression post-transcription and can be considered as a promising target for therapeutic purposes.
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spelling pubmed-81989162021-06-14 Oncogenic Role of miR-200c-3p in High-Grade Serous Ovarian Cancer Progression via Targeting the 3′-Untranslated Region of DLC1 Ankasha, Sheril June Shafiee, Mohamad Nasir Abdul Wahab, Norhazlina Raja Ali, Raja Affendi Mokhtar, Norfilza Mohd Int J Environ Res Public Health Article High-grade serous ovarian cancer (HGSC) is the most common ovarian cancer with highly metastatic properties. A small non-coding RNA, microRNA (miRNA) was discovered to be a major regulator in many types of cancers through binding at the 3′-untranslated region (3′UTR), leading to degradation of the mRNA. In this study, we sought to investigate the underlying mechanisms involved in the dysregulation of miR-200c-3p in HGSC progression and metastasis. We identified the upregulation of miR-200c-3p expression in different stages of HGSC clinical samples and the downregulation of the tumor suppressor gene, Deleted in Liver Cancer 1 (DLC1), expression. Over expression of miR-200c-3p in HGSC cell lines downregulated DLC1 but upregulated the epithelial marker, E-cadherin (CDH1). Based on in silico analysis, two putative binding sites were found within the 3′UTR of DLC1, and we confirmed the direct binding of miR-200c-3p to the target binding motif at position 1488–1495 bp of 3′UTR of DLC1 by luciferase reporter assay in a SKOV3 cell line co-transfected with vectors and miR-200c-3p mimic. These data showed that miR-200c-3p regulated the progression of HGSC by regulating DLC1 expression post-transcription and can be considered as a promising target for therapeutic purposes. MDPI 2021-05-27 /pmc/articles/PMC8198916/ /pubmed/34071861 http://dx.doi.org/10.3390/ijerph18115741 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ankasha, Sheril June
Shafiee, Mohamad Nasir
Abdul Wahab, Norhazlina
Raja Ali, Raja Affendi
Mokhtar, Norfilza Mohd
Oncogenic Role of miR-200c-3p in High-Grade Serous Ovarian Cancer Progression via Targeting the 3′-Untranslated Region of DLC1
title Oncogenic Role of miR-200c-3p in High-Grade Serous Ovarian Cancer Progression via Targeting the 3′-Untranslated Region of DLC1
title_full Oncogenic Role of miR-200c-3p in High-Grade Serous Ovarian Cancer Progression via Targeting the 3′-Untranslated Region of DLC1
title_fullStr Oncogenic Role of miR-200c-3p in High-Grade Serous Ovarian Cancer Progression via Targeting the 3′-Untranslated Region of DLC1
title_full_unstemmed Oncogenic Role of miR-200c-3p in High-Grade Serous Ovarian Cancer Progression via Targeting the 3′-Untranslated Region of DLC1
title_short Oncogenic Role of miR-200c-3p in High-Grade Serous Ovarian Cancer Progression via Targeting the 3′-Untranslated Region of DLC1
title_sort oncogenic role of mir-200c-3p in high-grade serous ovarian cancer progression via targeting the 3′-untranslated region of dlc1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198916/
https://www.ncbi.nlm.nih.gov/pubmed/34071861
http://dx.doi.org/10.3390/ijerph18115741
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