Zhilei Cui1, Zhen Liu2, Junxiang Zeng3, Shulin Zhang4, Lei Chen5, Guorui Zhang1, Weiguo Xu1, Lin Song6, Xuejun Guo7. 1. Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. 2. State Key Laboratory of Microbial Metabolism, School of Life Science and Biotechnology, Shanghai Jiao Tong University, China. 3. Department of Laboratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. 4. Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, China. 5. Department of Pathology, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. 6. Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. Electronic address: everlasting1981@126.com. 7. Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. Electronic address: guoxuejun@xinhuamed.com.cn.
Abstract
AIMS: The relationship between TRIM59 and drug resistance is elusive despite of its multiple uncovered roles in human cancers. Here we aimed to characterize the expression status of TRIM59 in gefitinib-resistant EGFR mutant lung adenocarcinoma cells and elucidate its mechanism underlying the drug resistance. MAIN METHODS: Gefitinib-resistant cell lines were established by progressive dosage. Relative expression of TRIM59 was determined by both real-time PCR and Western blot. Target gene knockdown was achieved by specific shRNAs. Cell viability was measured by MTT assay. Cell apoptosis was analyzed by flow cytometry with Annexin V/7-AAD double staining. Cell proliferation was determined by clonogenic formation assay. Migration and invasion capacities were detected using transwell chamber assay. Direct interaction between TRIM59 and STAT3 was analyzed by co-immunoprecipitation assay. KEY FINDINGS: We first observed overexpression of TRIM59 in gefitinib-resistant EGFR mutant lung adenocarcinoma cells. ShRNA-mediated knockdown of TRIM59 significantly inhibited cell viability and stimulated apoptosis. Meanwhile, TRIM59-deficiency suppressed cell migration and invasion. We further identified the interaction between TRIM59 and STAT3. TRIM59-deficiency remarkably impaired the activation of STAT3 signaling. STAT3-specific shRNAs significantly re-sensitized TRIM59-proficient EGFR mutant lung adenocarcinoma cells to gefitinib. SIGNIFICANCE: Our data characterized aberrant TRIM59 overexpression in gefitinib-resistance EGFR mutant lung adenocarcinoma cells, and indicated the potential involvement of TRIM59-STAT3 signaling in the occurrence of gefitinib-resistance.
AIMS: The relationship between TRIM59 and drug resistance is elusive despite of its multiple uncovered roles in humancancers. Here we aimed to characterize the expression status of TRIM59 in gefitinib-resistant EGFR mutant lung adenocarcinoma cells and elucidate its mechanism underlying the drug resistance. MAIN METHODS:Gefitinib-resistant cell lines were established by progressive dosage. Relative expression of TRIM59 was determined by both real-time PCR and Western blot. Target gene knockdown was achieved by specific shRNAs. Cell viability was measured by MTT assay. Cell apoptosis was analyzed by flow cytometry with Annexin V/7-AAD double staining. Cell proliferation was determined by clonogenic formation assay. Migration and invasion capacities were detected using transwell chamber assay. Direct interaction between TRIM59 and STAT3 was analyzed by co-immunoprecipitation assay. KEY FINDINGS: We first observed overexpression of TRIM59 in gefitinib-resistant EGFR mutant lung adenocarcinoma cells. ShRNA-mediated knockdown of TRIM59 significantly inhibited cell viability and stimulated apoptosis. Meanwhile, TRIM59-deficiency suppressed cell migration and invasion. We further identified the interaction between TRIM59 and STAT3. TRIM59-deficiency remarkably impaired the activation of STAT3 signaling. STAT3-specific shRNAs significantly re-sensitized TRIM59-proficient EGFR mutant lung adenocarcinoma cells to gefitinib. SIGNIFICANCE: Our data characterized aberrant TRIM59 overexpression in gefitinib-resistance EGFR mutant lung adenocarcinoma cells, and indicated the potential involvement of TRIM59-STAT3 signaling in the occurrence of gefitinib-resistance.
Authors: Karolina Łuczkowska; Katarzyna Ewa Sokolowska; Tomasz K Wojdacz; Bogusław Machaliński; Olga Taryma-Lesniak; Krzysztof Pastuszak; Anna Supernat; Jonas Bybjerg-Grauholm; Lise Lotte Hansen; Edyta Paczkowska Journal: Sci Rep Date: 2021-05-10 Impact factor: 4.379
Authors: Dongkyoo Park; Abu Syed Md Anisuzzaman; Andrew T Magis; Guo Chen; Maohua Xie; Guojing Zhang; Madhusmita Behera; Gabriel L Sica; Suresh S Ramalingam; Taofeek K Owonikoko; Xingming Deng Journal: Theranostics Date: 2021-07-25 Impact factor: 11.556