A tumor-specific modulation of heterogeneous ribonucleoprotein A0 promotes excessive mitosis and growth in colorectal cancer cells
Open Access
- 17 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 11 (4), 1-16
- https://doi.org/10.1038/s41419-020-2439-7
Abstract
RNA regulation mediating RNA-binding proteins (RBPs) have been shown to be related to the maintenance of homeostasis as well as cancer progression. However, the tumor-associated functions as well as the detailed mechanisms underlying the anti-tumor effects of most RBPs have yet to be explored. We herein report that the phosphorylated heterogeneous ribonucleoprotein (hnRNP) A0 promotes mitosis through the RAS-associated protein 3 GTPase-activating protein catalytic subunit 1 (RAB3GAP1)-Zeste white 10 interactor (ZWINT1) cascade. The downregulation assay of 20 representative hnRNPs, a major family of RNA-binding proteins, in colorectal cancer cells revealed that hnRNPA0 is a strong regulator of cancer cell growth. The tumor promotive function of hnRNPA0 was confirmed in gastrointestinal cancer cells, including pancreatic, esophageal, and gastric cancer cells, but not in non-cancerous cells. Flow cytometry and Western blotting analyses revealed that hnRNPA0 inhibited the apoptosis through the maintenance of G2/M phase promotion in colorectal cancer cells. A comprehensive analysis of mRNAs regulated by hnRNP A0 and immunostaining revealed that mitotic events were regulated by the hnRNPA0-RAB3GAP1 mRNA-mediated ZWINT-1 stabilization in colorectal cancer cells, but not in non-tumorous cells. The interaction of hnRNP A0 with mRNAs was dramatically changed by the deactivation of its phosphorylation site in cancer cells, but not in non-tumorous cells. Therefore, the tumor-specific biological functions characterized by the abnormal phosphorylation of RBPs are considered to be an attractive target for tumor treatment.This publication has 39 references indexed in Scilit:
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