Noncoding RNAs regulate alternative splicing in Cancer

Abstract

AS (alternative splicing) is a fundamental process by which a gene can generate multiple distinct mRNA transcripts to increase protein diversity. Defects in AS influence the occurrence and development of many diseases, including cancers, and are frequently found to participate in various aspects of cancer biology, such as promoting invasion, metastasis, apoptosis resistance and drug resistance. NcRNAs (noncoding RNAs) are an abundant class of RNAs that do not encode proteins. NcRNAs include miRNAs (microRNAs), lncRNAs (long noncoding RNAs), circRNAs (circular RNAs) and snRNAs (small nuclear RNAs) and have been proven to act as regulatory molecules that mediate cancer processes through AS. NcRNAs can directly or indirectly influence a plethora of molecular targets to regulate cis-acting elements, trans-acting factors, or pre-mRNA transcription at multiple levels, affecting the AS process and generating alternatively spliced isoforms. Consequently, ncRNA-mediated AS outcomes affect multiple cellular signaling pathways that promote or suppress cancer progression. In this review, we summarize the current mechanisms by which ncRNAs regulate AS in cancers and discuss their potential clinical applications as biomarkers and therapeutic targets.

Circular RNA: A promising new star for the diagnosis and treatment of colorectal cancer

“…AS mainly relies on splice bodies, splice sites, cis-acting elements, and trans-acting factors to participate in the proliferation, invasion, chemotherapy resistance, and apoptosis of various cancers. 67 A variety of circRNAs containing exons or introns can be generated by a single gene through alternative splicing. A large number of studies have found that circRNAs are covalently linked to upstream and downstream-specific splicing sites generated from standardized sequences in pre-mRNA or nonstandardized reverse splicing sequences that have potential for gene regulation.…”

CircRERE confers the resistance of multiple myeloma to bortezomib depending on the regulation of CD47 by exerting the sponge effect on miR-152-3p

“…Noncoding RNAs (ncRNAs) participate in all aspects of cancer biology, such as cell apoptosis, proliferation and drug resistance [5] . Circular RNAs (circRNAs) are covalently closed-loop ncRNAs without 5′ and 3′ ends, and they are produced by back-splicing of premessenger RNAs.…”

Functional Peptides Encoded by Long Non-Coding RNAs in Gastrointestinal Cancer

“…In recent years, many AS changes have been found to play an important role in the development of cancer. With the development of high-throughput sequencing and RNA-seq techniques, thousands of non-coding RNAs have been identified as critical for regulating AS at multiple levels in cancer ( 28 ). LncRNA DGCR5 binds directly to serine-and arginine-rich splicing factor 1(SRSF1) to increase its stability, thereby stimulating the Mcl-1 alternative splicing event to promoting the occurrence of esophageal squamous-cell carcinoma in vivo ( 29 ).…”