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

Sheril June Ankasha, Mohamad Nasir Shafiee, Norhazlina Abdul Wahab, Raja Affendi Raja Ali and Norfilza Mohd Mokhtar
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Sheril June Ankasha: Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
Mohamad Nasir Shafiee: Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
Norhazlina Abdul Wahab: Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
Raja Affendi Raja Ali: Gastroenterology Unit, Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
Norfilza Mohd Mokhtar: Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia

IJERPH, 2021, vol. 18, issue 11, 1-14

Abstract: 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.

Keywords: microRNA; miR-200c; ovarian neoplasms; target site; luciferase assay; metastasis; epithelial-mesenchymal transition; 3?untranslated regions (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
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