A-to-I edited miR-411-5p targets MET and promotes TKI response in NSCLC

Author:

Acunzo Mario1ORCID,Romano Giulia,Le Patricia1ORCID,Nigita Giovanni2ORCID,Saviana Michela,Micalo Lavender,Lovat Francesca2,Morales Daniel del Valle,Li Howard,Nana-Sinkam Patrick

Affiliation:

1. Virginia Commonwealth University

2. The Ohio State University

Abstract

Abstract The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor (TKR) frequently mutated in lung cancer. Despite initially favorable clinical responses of non-small cell lung cancer (NSCLC) patients harboring an EGFR mutation to treatment with tyrosine kinase inhibitors (TKIs), rapid resistance occurs mainly because of genetic alterations, including amplification of the hepatocyte growth factor receptor (MET). RNA post-transcriptional modifications that contribute to aberrant expression of MET in cancer are under-investigated. Among them, adenosine to inosine (A-to-I) RNA editing regulates RNA sequence, function, degradation, and structure. RNA editing has been observed in microRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional gene regulation. High throughput interrogation of the human genome allows for the identification of miRNA editing deregulation in cancer. However, the biological impact of edited miRNAs on lung cancer progression and drug resistance remains largely unknown. A reduction of A-to-I editing in position 5 of miR-411-5p has been identified in several cancers, including NSCLC. In this study, we determined that edited miR-411-5p negatively affects the ERK1/2 pathway, directly targets MET, and promotes EGFR TKI response in NSCLC.

Publisher

Research Square Platform LLC

Reference49 articles.

1. Cancer statistics, 2022;Siegel RL;CA Cancer J Clin,2022

2. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs;Lin JJ;J Thorac Oncol,2016

3. Molecular pathology of lung cancer: key to personalized medicine;Cheng L;Mod Pathol,2012

4. Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC);Gelatti ACZ;Lung Cancer,2019

5. Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer;Tan CS;Lancet Oncol,2015

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3