A Non-Coding RNA Network Involved in KSHV Tumorigenesis.

Julián Naipauer,Daria Salyakina,Martín E García Solá,Omar Coso,Martín C Abba,Sion Williams,Santas Rosario,Enrique A Mesri,Ezequiel Lacunza

doi:10.3389/fonc.2021.687629

Abstract

Regulatory pathways involving non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNA), have gained great relevance due to their role in the control of gene expression modulation. Using RNA sequencing of KSHV Bac36 transfected mouse endothelial cells (mECK36) and tumors, we have analyzed the host and viral transcriptome to uncover the role lncRNA-miRNA-mRNA driven networks in KSHV tumorigenesis. The integration of the differentially expressed ncRNAs, with an exhaustive computational analysis of their experimentally supported targets, led us to dissect complex networks integrated by the cancer-related lncRNAs Malat1, Neat1, H19, Meg3, and their associated miRNA-target pairs. These networks would modulate pathways related to KSHV pathogenesis, such as viral carcinogenesis, p53 signaling, RNA surveillance, and cell cycle control. Finally, the ncRNA-mRNA analysis allowed us to develop signatures that can be used to an appropriate identification of druggable gene or networks defining relevant AIDS-KS therapeutic targets.

Highlights

Non-coding RNAs are RNA transcripts that do not encode proteins and based on the length can be divided into two classes: small ncRNAs, with transcripts shorter than 200 nucleotides, and long ncRNAs, with transcripts longer than 200 nucleotides [1]
To identify changes in host long non-coding RNAs (lncRNA) expression profile, we analyzed the number of differentially expressed (DE; FC>1.5, p value
This mouse model allows for unique experimental comparisons in the same cell and KSHV TumorigenesisKaposi’s sarcoma (KS)-like mouse tumor types: 1) KSHV (−) cells versus KSHV (+) cells can be used to study KSHV mediated effects in vitro, 2) KSHV (−) tumors versus KSHV (+) tumors can be used to dissect the role of ncRNAs in tumorigenesis by comparing tumors driven by KSHV versus tumors driven by host mutations, 3) KSHV (+) cells grown in vitro and in tumors can be used to study in vitro versus in vivo variations induced by micro-environmental cues, and 4) KSHV (−) tumor cells versus KSHV (−) tumors can be used to study in vitro versus in vivo variations in the absence of KSHV [13]

Summary

Introduction

Non-coding RNAs (ncRNAs) are RNA transcripts that do not encode proteins and based on the length can be divided into two classes: small ncRNAs (sncRNAs), with transcripts shorter than 200 nucleotides, and long ncRNAs (lncRNAs), with transcripts longer than 200 nucleotides [1]. Different modes of interactions between lncRNAs and miRNAs have been reported: miRNA decay of lncRNAs, lncRNAs competing with mRNAs to bind to miRNAs, lncRNAs competing with miRNAs to bind to mRNA, and lncRNAs being shortened to miRNAs [2, 3]. All these interactions regulate the expression levels of mRNAs and in turn affect core protein signals, resulting in changes in the physiological functions of cells. KS is characterized by the proliferation of KSHV-infected spindle cells and profuse angiogenesis [6]

Methods

Results

Conclusion