A tumor-promotional molecular axis CircMAPKBP1/miR-17-3p/TGFβ2 activates autophagy pathway to drive tongue squamous cell carcinoma cisplatin chemoresistance

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2024-09-12 DOI:10.1016/j.canlet.2024.217230

Shule Xie , Yingru Li , Lianxi Mai , Xiaolin Gao , Guoxin Huang , Wenhao Sun , Liang Qiao , Bowen Li , Youyuan Wang , Zhaoyu Lin

{"title":"A tumor-promotional molecular axis CircMAPKBP1/miR-17-3p/TGFβ2 activates autophagy pathway to drive tongue squamous cell carcinoma cisplatin chemoresistance","authors":"Shule Xie , Yingru Li , Lianxi Mai , Xiaolin Gao , Guoxin Huang , Wenhao Sun , Liang Qiao , Bowen Li , Youyuan Wang , Zhaoyu Lin","doi":"10.1016/j.canlet.2024.217230","DOIUrl":null,"url":null,"abstract":"<div><div>Platinum-based chemotherapy is the first-line treatment for tongue squamous cell carcinoma (TSCC), but most patients rapidly develop resistance. Circular RNAs (circRNAs) are a class of critical regulators in the pathogenesis of several tumors, but their role in cisplatin resistance in TSCC has not been fully elucidated. Here we found that circMAPKBP1 was enriched in cisplatin resistant TSCC cells and was closely associated with enhanced autophagic activity. Functionally, silencing circMAPKBP1 significantly restored the chemosensitivity of cisplatin-resistant TSCC cells both in vitro and in vivo by suppressing autophagy. Mechanistically, circMAPKBP1 enhanced cisplatin sensitivity through the miR-17-3p/TGFβ2 axis by activating autophagy pathway. Data from clinical studies revealed that high expression of circMAPKBP1 and TGFβ2 was closely linked to a poor outcome in TSCC patients. We thus concluded that circMAPKBP1 is a tumor promoting factor and confers cisplatin sensitivity by activating the miR-17-3p/TGFβ2 axis-mediated autophagy. We propose that circMAPKBP1 may be a potential therapeutic target for TSCC.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"604 ","pages":"Article 217230"},"PeriodicalIF":9.1000,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0304383524006256","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Platinum-based chemotherapy is the first-line treatment for tongue squamous cell carcinoma (TSCC), but most patients rapidly develop resistance. Circular RNAs (circRNAs) are a class of critical regulators in the pathogenesis of several tumors, but their role in cisplatin resistance in TSCC has not been fully elucidated. Here we found that circMAPKBP1 was enriched in cisplatin resistant TSCC cells and was closely associated with enhanced autophagic activity. Functionally, silencing circMAPKBP1 significantly restored the chemosensitivity of cisplatin-resistant TSCC cells both in vitro and in vivo by suppressing autophagy. Mechanistically, circMAPKBP1 enhanced cisplatin sensitivity through the miR-17-3p/TGFβ2 axis by activating autophagy pathway. Data from clinical studies revealed that high expression of circMAPKBP1 and TGFβ2 was closely linked to a poor outcome in TSCC patients. We thus concluded that circMAPKBP1 is a tumor promoting factor and confers cisplatin sensitivity by activating the miR-17-3p/TGFβ2 axis-mediated autophagy. We propose that circMAPKBP1 may be a potential therapeutic target for TSCC.

查看原文本刊更多论文

促进肿瘤生长的分子轴CircMAPKBP1/miR-17-3p/TGFβ2激活自噬通路，驱动舌鳞状细胞癌的顺铂化疗抗性

铂类化疗是舌鳞状细胞癌（TSCC）的一线治疗方法，但大多数患者会迅速产生耐药性。环状 RNA（circRNA）是多种肿瘤发病机制中的一类关键调控因子，但它们在 TSCC 的顺铂耐药性中的作用尚未完全阐明。在这里，我们发现circMAPKBP1在顺铂耐药的TSCC细胞中富集，并与自噬活性增强密切相关。从功能上讲，沉默circMAPKBP1可通过抑制自噬作用显著恢复顺铂耐药TSCC细胞在体外和体内的化疗敏感性。从机理上讲，circMAPKBP1通过激活自噬通路，通过miR-17-3p/TGFβ2轴增强顺铂敏感性。临床研究数据显示，circMAPKBP1和TGFβ2的高表达与TSCC患者的不良预后密切相关。因此我们认为，circMAPKBP1是一种肿瘤促进因子，通过激活miR-17-3p/TGFβ2轴介导的自噬而赋予顺铂敏感性。我们建议将 circMAPKBP1 作为 TSCC 的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.