E2F1-induced ferritin heavy chain 1 pseudogene 3 (FTH1P3) accelerates non-small cell lung cancer gefitinib resistance
| Autor: | Guanying Zheng, Wenshu Chen, Wujin Li, Yun Ding, Pengjie Tu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Lung Neoplasms Pseudogene Biophysics Antineoplastic Agents Biology medicine.disease_cause Biochemistry 03 medical and health sciences 0302 clinical medicine Transcription (biology) Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Humans E2F1 neoplasms Molecular Biology Gene knockdown Microarray analysis techniques Gefitinib Cell Biology Middle Aged Prognosis Up-Regulation respiratory tract diseases Gene Expression Regulation Neoplastic 030104 developmental biology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research biology.protein Demethylase Female RNA Long Noncoding Carcinogenesis Chromatin immunoprecipitation |
| Zdroj: | Biochemical and Biophysical Research Communications. 530:624-631 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2020.07.044 |
| Popis: | Long noncoding RNAs (lncRNAs) have been identified to be critical regulator for various human diseases and emerging evidence illustrate the essential function of lncRNAs in the non-small cell lung cancer (NSCLC). Here, our research team tried to identify the roles of lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) in the NSCLC, as well as its molecular mechanism. LncRNA microarray analysis revealed that ferritin heavy chain 1 pseudogene 3 (FTH1P3) was up-regulated in the gefitinib-resistant cells (PC9/GR). Clinically, lncRNA FTH1P3 high-expression was closely correlated with NSCLC patients' unfavorable prognosis. Gain and loss of functional experiments revealed that FTH1P3 promoted the proliferation and invasion of NSCLC cells in vitro, and FTH1P3 knockdown repressed the tumor growth in vivo. Mechanistically, transcription factor E2F1 accelerated the transcription of FTH1P3. RNA immunoprecipitation and chromatin immunoprecipitation experiments showed that FTH1P3 can recruit lysine-specific demethylase 1 (LSD1) and epigenetically repress the TIMP3, thereby accelerating the tumorigenesis of NSCLC. In summary, these findings suggest that FTH1P3 plays a critical role in the gefitinib resistance and progression of NSCLC, providing a potential novel prognostic marker for NSCLC. |
| Databáze: | OpenAIRE |
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