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

• Published in: International journal of molecular sciences Vol. 21; no. 19; p. 7120
• Main Authors: Panza, Anna, Castellana, Stefano, Biscaglia, Giuseppe, Piepoli, Ada, Parca, Luca, Gentile, Annamaria, Latiano, Anna, Mazza, Tommaso, Perri, Francesco, Andriulli, Angelo, Palmieri, Orazio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2020; MDPI
• Subjects: Adenoma; Aged; Algorithms; Apoptosis; Autoantigens - genetics; Biomarkers; Biomarkers, Tumor - genetics; Cell cycle; Cell Cycle Proteins - genetics; Chromosome 13; Chromosome translocations; Colonoscopy; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Epigenetics; Female; fusion genes; Gene expression; Gene Expression Regulation, Neoplastic; Gene Fusion; Gene Regulatory Networks; Genetic aspects; Genetic transcription; Genomics; Health aspects; Humans; lncRNAs; Male; Medical prognosis; Metastasis; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; MRPS31P5; Neoplasms, Multiple Primary - genetics; Non-coding RNA; Nucleotide sequence; Polyps; Principal components analysis; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Ribosomal Proteins - genetics; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-Seq; sporadic CRC; synchronous lesions; Transcription; Transcription, Genetic - genetics; Transcriptome; Transcriptomes; Tumors; United States; fusion genes; lncRNAs; synchronous lesions; sporadic CRC; RNA-Seq; MRPS31P5
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21197120

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.