Transcriptome and Gene Fusion Analysis of Synchronous Lesions Reveals lncMRPS31P5 as a Novel Transcript Involved in Colorectal Cancer

Anna Panza,Giuseppe Biscaglia,Francesco Perri,Annamaria Gentile,Orazio Palmieri,Angelo Andriulli,Ada Piepoli,Stefano Castellana,Anna Latiano,Tommaso Mazza,Luca Parca

doi:10.3390/ijms21197120

Abstract

Fusion genes and epigenetic regulators (i.e., miRNAs and long non-coding RNAs) constitute essential pieces of the puzzle of the tumor genomic landscape, in particular in mechanisms behind the adenoma-to-carcinoma progression of colorectal cancer (CRC). In this work, we aimed to identify molecular signatures of the different steps of sporadic CRC development in eleven patients, of which synchronous samples of adenomas, tumors, and normal tissues were analyzed by RNA-Seq. At a functional level, tumors and adenomas were all characterized by increased activity of the cell cycle, cell development, cell growth, and biological proliferation functions. In contrast, organic survival and apoptosis-related functions were inhibited both in tumors and adenomas at different levels. At a molecular level, we found that three individuals shared a tumor-specific fusion named MRPS31-SUGT1, generated through an intra-chromosomal translocation on chromosome 13, whose sequence resulted in being 100% identical to the long non-coding RNA (lncRNA) MRPS31P5. Our analyses suggest that MRPS31P5 could take part to a competitive endogenous (ce)RNA network by acting as a miRNA sponge or/and as an interactor of other mRNAs, and thus it may be an important gene expression regulatory factor and could be used as a potential biomarker for the detection of early CRC events.

Highlights

Sporadic colorectal cancer (CRC) is the third most prevalent human malignancy worldwide, with approximately 1.8 million new cases and 900,000 deaths per year [1]
Colorectal adenoma involved in tumor progression is generally transformed to become malignant, but, in about 12.7% of patients with single CRC, adenoma remnants are conserved into the carcinoma
Recent studies have shown that long non-coding RNA (lncRNA) are involved in different stages of CRC, from adenoma to invasive cancer, and that they could function as competitive endogenous RNAs in CRC progression [23]. It remains to be clarified whether different molecular signatures are distinctive of the several steps involved in the progressive evolution from the adenoma to the carcinoma sequence development. We evaluated this issue in CRC patients with sporadic synchronous lesions by whole transcriptome sequencing (RNA-Seq) analysis

Summary

Introduction

Sporadic colorectal cancer (CRC) is the third most prevalent human malignancy worldwide, with approximately 1.8 million new cases and 900,000 deaths per year [1]. Sporadic CRC represents about two-thirds of all CRC cases [3]. CRC progresses as a multistep process arising from benign adenomatous polyps (adenomas) and developing into locally invasive and metastatic cancer. Colorectal adenoma involved in tumor progression is generally transformed to become malignant, but, in about 12.7% of patients with single CRC, adenoma remnants are conserved into the carcinoma. About one fifth of patients with single CRC is found to harbor synchronous adenomas during the diagnostic colonoscopy [4,5]

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