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

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.

Genomic Alterations Affecting Competitive Endogenous RNAs (ceRNAs) and Regulatory Networks (ceRNETs) with Clinical Implications in Triple-Negative Breast Cancer (TNBC)

“…While fusions in cancer can often result in an aberrant expression of oncogenic coding genes, they can also result in an aberrant generation or expression of non-coding genes with relevant regulatory functions. For example, a tumor-specific fusion, MRPS31-SUGT1, resulting from an intra-chromosomal translocation on chromosome 13, generates the previously identified lncRNA MRPS31P5 [ 38 ]. This fusion-generated lncRNA is implicated in a ceRNA network with several cancer-related miRNAs.…”

Potential of Mitochondrial Ribosomal Genes as Cancer Biomarkers Demonstrated by Bioinformatics Results

“…A tumor-specific gene fusion named MRPS31-SUGT1, generated by an intrachromosomal translocation on chromosome 13 and whose sequence was 100% identical to that of the lncRNA MRPS31P5, was discovered. MRPS31P5 may be an important gene expression regulator and is a potential biomarker for detecting early CRC events (63). Intimal sarcoma is a rare, histologically heterogeneous tumor that usually originates from the pulmonary artery.…”

Crosstalk of Oxidative Phosphorylation-Related Subtypes, Establishment of a Prognostic Signature and Immune Infiltration Characteristics in Colorectal Adenocarcinoma

“…Colorectal cancer (CRC) is the world’s top three malignancies in terms of incidence rate and mortality, respectively, accounting for 10.0% and 9.4% of the total incidence rate and mortality of cancer that occurred in 2020 [ 1 ]. CRC is heterogeneous and involves many pathogenic mechanisms, including somatic mutation, gene fusion, genetic instability and epigenetic changes [ 2 , 3 , 4 ]. In the new CRC diagnosis, metastatic disease occurred in 20% of patients, and metastatic disease later occurred in another 25% of patients with localized disease [ 5 ].…”