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FOXO3-induced oncogenic lncRNA CASC9 enhances gefitinib resistance of non-small-cell lung cancer through feedback loop.
Bing, Zhongxing; Han, Jiashu; Zheng, Zhibo; Liang, Naixin.
Affiliation
  • Bing Z; Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing 100730, China.
  • Han J; Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing 100730, China.
  • Zheng Z; Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing 100730, China.
  • Liang N; Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing 100730, China. Electronic address: liangnaixin.edu@aliyun.cm.
Life Sci ; 287: 120012, 2021 Dec 15.
Article in En | MEDLINE | ID: mdl-34619168
ABSTRACT
Gefitinib is tyrosine kinase inhibitor of epidermal growth factor receptor, which exhibits notable clinical efficacy in non-small-cell lung cancer (NSCLC) treatment. However, gefitinib resistance is a critical obstacle for NSCLC targeted therapy. Here, we investigated the biological functions and mechanisms of lncRNA CASC9 in NSCLC gefitinib resistance. Screening analysis and RT-qPCR demonstrated that CASC9 was up-regulated in the gefitinib-resistant NSCLC cells (PC9/GR). Moreover, high-expression of CASC9 acted as an unfavorable factor for NSCLC patients. Functionally, CASC9 promoted the proliferation and gefitinib resistance of PC9/GR cells in vitro, and knockdown of CASC9 repressed the tumor growth in vivo. Mechanistically, CASC9 epigenetically promoted the FOXO3 expression via inhibiting miR-195-5p. In turn, transcription factor FOXO3 bound with the promoter region of CASC9 to enhance CASC9 transcriptional level, thereby forming CASC9/miR-195-5p/FOXO3 positive feedback loop. In conclusion, our research identified the regulation of CASC9/miR-195-5p/FOXO3 feedback loop on NSCLC gefitinib resistance, which might help researchers develop potential therapeutic targets for NSCLC.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Non-Small-Cell Lung / RNA, Long Noncoding / Carcinogenesis / Forkhead Box Protein O3 / Gefitinib / Lung Neoplasms Type of study: Prognostic_studies Limits: Aged / Animals / Female / Humans / Male / Middle aged Language: En Journal: Life Sci Year: 2021 Type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Non-Small-Cell Lung / RNA, Long Noncoding / Carcinogenesis / Forkhead Box Protein O3 / Gefitinib / Lung Neoplasms Type of study: Prognostic_studies Limits: Aged / Animals / Female / Humans / Male / Middle aged Language: En Journal: Life Sci Year: 2021 Type: Article Affiliation country: China