Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell lines

Oncotarget
Ángela L Riffo-CamposJosefa Castillo

Abstract

Mutation-driven activation of KRAS is crucial to cancer development. The human gene yields four mRNA splicing isoforms, 4A and 4B being translated to protein. Their different properties and oncogenic potential have been studied, but the mechanisms deciding the ratio 4A/4B are not known. To address this issue, the expression of the four KRAS isoforms was determined in 9 human colorectal cancer cell lines. HCT116 and SW48 were further selected because they present the highest difference in the ratio 4A/4B (twice as much in HCT116 than in SW48). Chromatin structure was analysed at the exon 4A, characteristic of isoform 4A, at its intronic borders and at the two flanking exons. The low nucleosome occupancy at exon 4A in both cell lines may result in a fast transcriptional rate, which would explain the general lower abundance of isoform 4A, also found in cells and tissues by other authors, but due to its similarity between both cell lines, chromatin structure does not influence alternative splicing. DNA methylation downstream exon 4A significantly differs in HCT116 and SW48 cells, but the CCCTC-binding factor, which affects the processivity of RNA polymerase and the alternative splicing, does not bind the differentially methylated s...Continue Reading

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Citations

Aug 11, 2020·Cancer Metastasis Reviews·Erzsébet Rásó
Jan 3, 2021·Cellular and Molecular Life Sciences : CMLS·Subhashis NatuaSanjeev Shukla

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Methods Mentioned

BETA
GTPase
sequence-based prediction
PCR
acetylation
PCRs
immunoprecipitation

Software Mentioned

ENSEMBL
Epidesigner
ChIP
Nuc
NuPoP

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