The Identification of RNA-Binding Proteins Functionally Associated with Tumor Progression in Gastrointestinal Cancer

Previous investigations have indicated that RNA-binding proteins (RBPs) are key molecules for the development of organs, differentiation, cell growth and apoptosis in cancer cells as well as normal cells. A bioinformatics analysis based on the mRNA expression and a somatic mutational database reveal...

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Bibliographic Details
Main Authors: Hiroaki Konishi, Shin Kashima, Takuma Goto, Katsuyoshi Ando, Aki Sakatani, Hiroki Tanaka, Nobuhiro Ueno, Kentaro Moriichi, Toshikatsu Okumura, Mikihiro Fujiya
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Cancers
Subjects:
RBP
Online Access:https://www.mdpi.com/2072-6694/13/13/3165
Description
Summary:Previous investigations have indicated that RNA-binding proteins (RBPs) are key molecules for the development of organs, differentiation, cell growth and apoptosis in cancer cells as well as normal cells. A bioinformatics analysis based on the mRNA expression and a somatic mutational database revealed the association between aberrant expression/mutations of RBPs and cancer progression. However, this method failed to detect functional alterations in RBPs without changes in the expression, thus leading to false negatives. To identify major tumor-associated RBPs, we constructed an siRNA library based on the database of RBPs and assessed the influence on the growth of colorectal, pancreatic and esophageal cancer cells. A comprehensive analysis of siRNA functional screening findings using 1198 siRNAs targeting 416 RBPs identified 41 RBPs in which 50% inhibition of cell growth was observed in cancer cells. Among these RBPs, 12 showed no change in the mRNA expression and no growth suppression in non-cancerous cells when downregulated by specific siRNAs. We herein report for the first time cancer-promotive RBPs identified by a novel functional assessment using an siRNA library of RBPs combined with expressional and mutational analyses.
ISSN:2072-6694