The HNRNPA2B1-MST1R-Akt axis contributes to epithelial-to-mesenchymal transition in head and neck cancer.

Laboratory Investigation; a Journal of Technical Methods and Pathology
Amit GuptaSanjeev Shukla

Abstract

The deregulation of splicing factors and alternative splicing are increasingly viewed as major contributory factors in tumorigenesis. In this study, we report overexpression of a key splicing factor, heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1), and thereby misregulation of alternative splicing, which is associated with the poor prognosis of head and neck cancer (HNC). The role of HNRNPA2B1 in HNC tumorigenesis via deregulation of alternative splicing is not well understood. Here, we found that the CRISPR/Cas9-mediated knockout of HNRNPA2B1 results in inhibition of HNC cells growth via the misregulation of alternative splicing of MST1R, WWOX, and CFLAR. We investigated the mechanism of HNRNPA2B1-mediated HNC cells growth and found that HNRNPA2B1 plays an important role in the alternative splicing of a proto-oncogene, macrophage stimulating 1 receptor (MST1R), which encodes for the recepteur d'origine nantais (RON), a receptor tyrosine kinase. Our results indicate that HNRNPA2B1 mediates the exclusion of cassette exon 11 from MST1R, resulting in the generation of RON∆165 isoform, which was found to be associated with the activation of Akt/PKB signaling in HNC cells. Using the MST1R-minigene model, we validated the ro...Continue Reading

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Citations

Jul 20, 2021·Frontiers in Cell and Developmental Biology·Kexin LiWei Cui
Oct 8, 2021·Frontiers in Cell and Developmental Biology·Sandhya YadavSanjeev Shukla
Oct 12, 2021·Frontiers in Genetics·Jingzhi TangHuiming Xu

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Methods Mentioned

BETA
electrophoresis
PCR
RNAseq
transfection

Software Mentioned

Capture
GraphPad Prism5
ImageJ
IDT Primer Quest
MiPanda

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