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Aberrant RNA Splicing in Cancer and Drug Resistance
More than 95% of the 20,000 to 25,000 transcribed human genes undergo alternative RNA splicing, which increases the diversity of the proteome. Isoforms derived from the same gene can have distinct and, in some cases, opposing functions. Accumulating evidence suggests that aberrant RNA splicing is a...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266310/ https://www.ncbi.nlm.nih.gov/pubmed/30463359 http://dx.doi.org/10.3390/cancers10110458 |
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author | Wang, Bi-Dar Lee, Norman H. |
author_facet | Wang, Bi-Dar Lee, Norman H. |
author_sort | Wang, Bi-Dar |
collection | PubMed |
description | More than 95% of the 20,000 to 25,000 transcribed human genes undergo alternative RNA splicing, which increases the diversity of the proteome. Isoforms derived from the same gene can have distinct and, in some cases, opposing functions. Accumulating evidence suggests that aberrant RNA splicing is a common and driving event in cancer development and progression. Moreover, aberrant splicing events conferring drug/therapy resistance in cancer is far more common than previously envisioned. In this review, aberrant splicing events in cancer-associated genes, namely BCL2L1, FAS, HRAS, CD44, Cyclin D1, CASP2, TMPRSS2-ERG, FGFR2, VEGF, AR and KLF6, will be discussed. Also highlighted are the functional consequences of aberrant splice variants (BCR-Abl35INS, BIM-γ, IK6, p61 BRAF V600E, CD19-∆2, AR-V7 and PIK3CD-S) in promoting resistance to cancer targeted therapy or immunotherapy. To overcome drug resistance, we discuss opportunities for developing novel strategies to specifically target the aberrant splice variants or splicing machinery that generates the splice variants. Therapeutic approaches include the development of splice variant-specific siRNAs, splice switching antisense oligonucleotides, and small molecule inhibitors targeting splicing factors, splicing factor kinases or the aberrant oncogenic protein isoforms. |
format | Online Article Text |
id | pubmed-6266310 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62663102018-12-03 Aberrant RNA Splicing in Cancer and Drug Resistance Wang, Bi-Dar Lee, Norman H. Cancers (Basel) Review More than 95% of the 20,000 to 25,000 transcribed human genes undergo alternative RNA splicing, which increases the diversity of the proteome. Isoforms derived from the same gene can have distinct and, in some cases, opposing functions. Accumulating evidence suggests that aberrant RNA splicing is a common and driving event in cancer development and progression. Moreover, aberrant splicing events conferring drug/therapy resistance in cancer is far more common than previously envisioned. In this review, aberrant splicing events in cancer-associated genes, namely BCL2L1, FAS, HRAS, CD44, Cyclin D1, CASP2, TMPRSS2-ERG, FGFR2, VEGF, AR and KLF6, will be discussed. Also highlighted are the functional consequences of aberrant splice variants (BCR-Abl35INS, BIM-γ, IK6, p61 BRAF V600E, CD19-∆2, AR-V7 and PIK3CD-S) in promoting resistance to cancer targeted therapy or immunotherapy. To overcome drug resistance, we discuss opportunities for developing novel strategies to specifically target the aberrant splice variants or splicing machinery that generates the splice variants. Therapeutic approaches include the development of splice variant-specific siRNAs, splice switching antisense oligonucleotides, and small molecule inhibitors targeting splicing factors, splicing factor kinases or the aberrant oncogenic protein isoforms. MDPI 2018-11-20 /pmc/articles/PMC6266310/ /pubmed/30463359 http://dx.doi.org/10.3390/cancers10110458 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Wang, Bi-Dar Lee, Norman H. Aberrant RNA Splicing in Cancer and Drug Resistance |
title | Aberrant RNA Splicing in Cancer and Drug Resistance |
title_full | Aberrant RNA Splicing in Cancer and Drug Resistance |
title_fullStr | Aberrant RNA Splicing in Cancer and Drug Resistance |
title_full_unstemmed | Aberrant RNA Splicing in Cancer and Drug Resistance |
title_short | Aberrant RNA Splicing in Cancer and Drug Resistance |
title_sort | aberrant rna splicing in cancer and drug resistance |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266310/ https://www.ncbi.nlm.nih.gov/pubmed/30463359 http://dx.doi.org/10.3390/cancers10110458 |
work_keys_str_mv | AT wangbidar aberrantrnasplicingincanceranddrugresistance AT leenormanh aberrantrnasplicingincanceranddrugresistance |