Long Non-Coding RNA MAGI2-AS3 is a New Player with a Tumor Suppressive Role in High Grade Serous Ovarian Carcinoma

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.

MAGI2‐AS3 inhibits breast cancer by downregulating DNA methylation of MAGI2

“…By analyzing the RNA-seq data of breast cancer tissues in the TCGA database, we found lncRNA MAGI2-AS3, which is downregulated in breast cancer tissues. This shows that MAGI2 was not only down- lung cancer (Hao & Yang, 2019), bladder cancer (Zhu et al, 2018), and ovarian cancer (Gokulnath et al, 2019). In breast cancer, MAGI2-AS3 can inhibit tumor cell proliferation by activating the Fas/FasL pathway to mediate cell apoptosis (Y.…”

LBX2-AS1 Promotes Ovarian Cancer Progression by Facilitating E2F2 Gene Expression via MIR-455-5P and MIR-491-5P Sponging

“…In 2018, two different research groups proposed this lncRNA as a biomarker for poor prognosis in glioma [23][24], after which this lncRNA was found to participate in the development of esophageal squamous cell carcinoma [25] , non-small cell lung cancer [26], gastric cancer [14] and hepatocellular carcinoma [13]. Notably, Zhang et al explored LBX2-AS1 expression level in esophageal squamous cell carcinoma and the correlation between LBX2-AS1 expression level and patients overall survival using the data in TCGA esophageal squamous cell carcinoma [12], which inspired us to perform a similar pilot study on ovarian cancer. In this research, we found that, based on the data we obtained from TCGA database and our clinical record, the expression level of LBX2-AS1 was frequently increased in ovarian cancer, and patients who have high LBX2-AS1 expression levels in their ovarian cancer tissue specimens showed a decreased overall survival, suggesting the cancer promoting role of this lncRNA in ovarian cancer.…”

“…MicroRNAs (miRNAs) are small RNAs (< 200 nt) that are known to repress the expression of their target genes by interacting with their binding sites on the target gene mRNAs and suppressing protein translation [6], and lncRNAs could regulate the expression of miRNA target genes by competitively binding to these miRNAs [7] . LncRNAs including FLVCR1-AS1, HOXD-AS1, MLK7-AS1 and HOTAIR [8][9][10][11] have been reported to promote ovarian cancer development through such mechanisms, while some other lncRNAs, such as MAGI2-AS3 [12], showed a cancer-suppressive role in ovarian cancer development.…”

A new long-read dog assembly uncovers thousands of exons and functional elements missing in the previous reference

“…This sequence is composed of a set of complex structural variants (Fig 1d) and overlaps with the MAGI2. Various somatic genetic alterations in this gene are observed in ovarian, breast and colorectal carcinomas [6][7][8].…”