The Biological and Clinical Role of the Long Non-Coding RNA LOC642852 in Ovarian Carcinoma.

Natalie Filippov-Levy,Reuven Reich,Ben Davidson

doi:10.3390/ijms21155237

Abstract

The objective of the present study was to analyze the biological and clinical role of the long non-coding RNA LOC642852 in ovarian carcinoma (OC). LOC642852 expression was analyzed in seven OC cell lines (OVCAR-3, OVCAR-8, OVCA 433, OVCA 429, OC 238, DOV13, ES-2) and 139 high-grade serous carcinoma (HGSC) specimens (85 effusions, 54 surgical specimens). Following LOC642852 knockout (KO) using the CRISPR/Cas9 system, OVCAR-8 HGSC cells were analyzed for spheroid formation, migration, invasion, proliferation, matrix metalloproteinase (MMP) activity, and expression of cell signaling proteins. OVCAR-8 cells with LOC642852 KO were significantly less motile and less invasive compared to controls, with no differences in spheroid formation, proliferation, or matrix metalloproteinase (MMP) activity. Total Akt and Erk levels were comparable in controls and KO cells, but their phosphorylation was significantly increased in the latter. In clinical specimens, LOC642852 was overexpressed in ovarian tumors and omental/peritoneal metastases compared to effusion specimens (p = 0.013). A non-significant trend for shorter overall (p = 0.109) and progression-free (p = 0.056) survival was observed in patients with HGSC effusions with high LOC642852 levels. Bioinformatics analysis showed potential roles for LOC642852 as part of the TLE3/miR-221-3p ceRNA network and in relation to the FGFR3 protein. In conclusion, LOC642852 inactivation via CRISPR/Cas9 affects cell signaling, motility, and invasion in HGSC cells. LOC642852 is differentially expressed in HGSC cells at different anatomical sites. Its potential role in regulating the TLE3/miR-221-3p ceRNA network and FGFR3 merits further research.

Highlights

A small part of the genome encodes proteins, while the rest is transcribed to non-coding RNA
Recent research has documented the biological role of Long non-coding RNAs (lncRNAs) in ovarian carcinoma (OC) [7,8,9], and several studies have demonstrated an association between lncRNA expression and patient survival in this cancer [11,12]
There are currently between 32 and 58 lncRNAs that have been reported to have a role in OC pathogenesis [7,8,9]

Summary

Introduction

A small part of the genome encodes proteins, while the rest is transcribed to non-coding RNA. Long non-coding RNAs (lncRNAs) are non-coding RNAs containing more than 200 nucleotides. LncRNA genes have protein-coding characteristic chromatin marks (e.g., H3K4me at promoters) and are transcribed and processed as mRNA, undergoing splicing, capping, and polyadenylation [1]. Several functions of lncRNAs have been discovered, including chromatin regulation, mRNA decoy, regulation of protein activity, and scaffolding. LncRNA are precursors for small RNA and miRNA, and function as sponges or part of competing endogenous RNAs (ceRNAs), a complex interaction network between mRNA, lncRNA, and microRNA [2]. LncRNA have been found to undergo mutation and have aberrant expression [3]

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