Reference - Detail
| RRC ID | 83634 |
|---|---|
| Author | Kirimura S, Kurata M, Ishibashi H, Taniguchi Y, Kinowaki Y, Sugita K, Okubo K. |
| Title | Cytoplasmic HuR Expression Enhances Chemoresistance in Pleural Mesothelioma Through Increased Expression of CALB2, Promotion of the E2F Pathway, and Suppression of the p53 Pathway. |
| Journal | Thorac Cancer |
| Abstract |
INTRODUCTION:Chemotherapy is crucial for treating pleural mesothelioma; however, the outcomes are poor, necessitating an urgent need to study the mechanism of chemotherapy resistance in mesothelioma cells. Human antigen R (HuR), an RNA-binding protein and key post-transcriptional regulator of mRNA, is linked to poor prognosis in cancers like mesothelioma. We investigated the involvement of cytoplasmic HuR expression in drug resistance mechanisms in mesothelioma. METHODS:We retrospectively evaluated cytoplasmic HuR expression in 30 patients with pleural mesothelioma who underwent surgical resection using immunohistochemistry. We also examined the role of forced cytoplasmic expression of HuR in drug resistance using mesothelioma cell lines and performed RNA-Seq analysis to identify gene expression changes responsible for drug resistance acquisition via HuR cytoplasmic expression. RESULTS:Patients with mesotheliomas who expressed cytoplasmic HuR exhibited significantly worse disease-free survival following post-operative chemotherapy. Forced cytoplasmic HuR expression in mesothelioma cell lines increased chemotherapy resistance through increased expression of CALB2, upregulation of the E2F pathway and suppression of the p53 pathway. CONCLUSIONS:Cytoplasmic HuR expression increases the chemoresistance and postoperative recurrence risk of pleural mesothelioma, making it a potential biomarker for predicting therapeutic prognosis. However, the mechanism of HuR transfer to the cytoplasm remains unclear for therapeutic application. |
| Volume | 16(7) |
| Pages | e70062 |
| Published | 2025-4-1 |
| DOI | 10.1111/1759-7714.70062 |
| PMID | 40200787 |
| PMC | PMC11979354 |
| MeSH | Aged Biomarkers, Tumor / metabolism Cell Line, Tumor Cytoplasm / metabolism Drug Resistance, Neoplasm* E2F Transcription Factors* / genetics E2F Transcription Factors* / metabolism ELAV-Like Protein 1* / genetics ELAV-Like Protein 1* / metabolism Female Gene Expression Regulation, Neoplastic Humans Male Mesothelioma* / drug therapy Mesothelioma* / genetics Mesothelioma* / metabolism Mesothelioma* / pathology Mesothelioma, Malignant Middle Aged Pleural Neoplasms* / drug therapy Pleural Neoplasms* / genetics Pleural Neoplasms* / metabolism Pleural Neoplasms* / pathology Prognosis Retrospective Studies Signal Transduction Tumor Suppressor Protein p53* / metabolism |
| IF | 2.524 |
| Resource | |
| Human and Animal Cells | ACC-MESO-1(RCB2292) |