Upregulation of TRNA-Ser-AGA-2-1 Promotes Malignant Behavior in Normal Bronchial Cells

Overview

Journal Front Mol Biosci

Specialty Biology

Date 2022 May 19

PMID 35586191

Authors

Mafalda Santos

Ana Fidalgo

Ana Sofia Varanda

Ana Raquel Soares

Gabriela M Almeida

Diana Martins

Nuno Mendes

Carla Oliveira

Manuel A S Santos

Affiliations

Soon will be listed here.

Abstract

Serine tRNAs (tRNA) are frequently overexpressed in tumors and associated with poor prognosis and increased risk of recurrence in breast cancer. Impairment of tRNA biogenesis and abundance also impacts proteome homeostasis, and activates protein quality control systems. Herein, we aimed at testing whether increasing tRNA abundance could foster tumor establishment through activation of the UPR. In order to do so, firstly we confirmed that the expression of tRNA-Ser-AGA-2-1 [hereafter tRNA(AGA)] was upregulated by 1.79-fold in Stage I NSCLC tumors when compared to normal adjacent tissue. To study the impact of tRNA(AGA) in early stage tumorigenesis, we induced its upregulation in a non-tumoral bronchial cell line, BEAS-2B. Upregulation of this tRNA increased cellular proliferation and protein synthesis rate, driven by eIF2 dephosphorylation and ATF4 activation downstream of PERK signaling. Futhermore, tRNA(AGA) enhanced transformation potential , and promoted the establishment of slow growing tumors with aggressive features in nude mice. Our work highlights the importance of studying tRNA deregulation on early stage tumorigenesis, as they may be potential malignancy and aggressiveness biomarkers.

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