Abstract
High-Grade Serous Ovarian Carcinoma (HGSC) is the most incidental and lethal subtype of epithelial ovarian cancer (EOC) with a high mortality rate of nearly 65%. Recent findings aimed at understanding the pathogenesis of HGSC have attributed its principal source as the Fallopian Tube (FT). To further comprehend the exact mechanism of carcinogenesis, which is still less known, we performed a transcriptome analysis comparing FT and HGSC. Our study aims at exploring new players involved in the development of HGSC from FT, along with their signaling network, and we chose to focus on non-coding RNAs. Non-coding RNAs (ncRNAs) are increasingly observed to be the major regulators of several cellular processes and could have key functions as biological markers, as well as even a therapeutic approach. The most physiologically relevant and significantly dysregulated non-coding RNAs were identified bioinformatically. After analyzing the trend in HGSC and other cancers, MAGI2-AS3 was observed to be an important player in EOC. We assessed its tumor-suppressive role in EOC by means of various assays. Further, we mapped its signaling pathway using its role as a miRNA sponge to predict the miRNAs binding to MAGI2AS3 and showed it experimentally. We conclude that MAGI2-AS3 acts as a tumor suppressor in EOC, specifically in HGSC by sponging miR-15-5p, miR-374a-5p and miR-374b-5p, and altering downstream signaling of certain mRNAs through a ceRNA network.
Highlights
Epithelial Ovarian Cancer (EOC), accounting for most of the ovarian cancers (OC) [1], is the most lethal gynecological malignancy [2]
This is of great significance especially in highly lethal ovarian cancers where there is much to be gleaned from pathogenesis of High-Grade Serous Ovarian Cancer (HGSC)
Differential expression analysis was performed between SKOV-3 (Epithelial Ovarian Cancer cell line) and FT-194 (Fallopian Tube cell line) [23], using RNA sequencing data and several differentially regulated non-coding RNAs were identified by filtering for non-coding RNAs annotated in the Ensembl BioMart databank
Summary
Epithelial Ovarian Cancer (EOC), accounting for most of the ovarian cancers (OC) [1], is the most lethal gynecological malignancy [2] It is the eighth most incidental and the most common cause of death in women [3], with about half the patients diagnosed with the disease succumbing to it within the 5 years [4,5]. High-Grade Serous Ovarian Cancer (HGSC), one of EOC subtypes, accounts for around 70% of incidence and 65% mortality of all ovarian cancers [6,7] This is attributed to very late diagnosis, almost always after the disease metastasis, often showing an abdominal spread [8]. One of the determining evidence was the presence of Serous Tubal Intraepithelial Carcinoma (STIC) in the Fallopian tubes of around 60% of HGSC patients [10] and tubal ligation seemed to reduce the incidence of HGSC in patients showing BRCA1/BRCA2 mutations [9]
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