VPS33B modulates c-Myc/p53/miR-192-3p to target CCNB1 suppressing the growth of non-small cell lung cancer
| Autor: | Zhen Liu, Shu Liu, Guifang Yu, Jingwen Jiang, Rongcheng Luo, Shuting Deng, Yinghao Wen, Jiahao Liu, Yan Xu, Shulu Hu, Ping Xu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway p53 miR-192-3p Colorectal cancer Cell CCNB1 03 medical and health sciences 0302 clinical medicine Drug Discovery medicine VPS33B Lung cancer Transcription factor non-small cell lung cancer Chemistry Cell growth lcsh:RM1-950 medicine.disease respiratory tract diseases 030104 developmental biology medicine.anatomical_structure lcsh:Therapeutics. Pharmacology Nasopharyngeal carcinoma 030220 oncology & carcinogenesis Cancer research Molecular Medicine Adenocarcinoma Original Article |
| Zdroj: | Molecular Therapy: Nucleic Acids, Vol 23, Iss, Pp 324-335 (2021) Molecular Therapy. Nucleic Acids |
| ISSN: | 2162-2531 |
| Popis: | VPS33B is reported to be a tumor suppressor in hepatocellular carcinoma, nasopharyngeal carcinoma, colon cancer, and lung adenocarcinoma. Here, we observed that reduced VPS33B protein level was an unfavorable factor that promoted the pathogenesis of non-small cell lung cancer (NSCLC) in clinical specimens. We achieved lentivirus-mediated stable overexpression of VPS33B in NSCLC cells. Increased VPS33B reduced cell cycle transition and cell proliferation of NSCLC cells in vivo and in vitro. Knocking down VPS33B restored cell growth. Mechanism analysis indicated that miR-192-3p was induced by VPS33B and acted as a tumor suppressor of cell growth in NSCLC. Further, c-Myc or p53 was identified as a transcription factor that bound to the miR-192-3p promoter and regulated its expression. miR-192-3p directly targeted cell cycle-promoted factor CCNB1 and suppressed NSCLC cell growth. VPS33B modulated c-Myc/p53/miR-192-3p signaling to target CCNB1 by reducing activation of the Ras/ERK pathway. Our study reveals a novel molecular basis for VPS33B as a tumor suppressor to participate in the pathogenesis of NSCLC. Graphical Abstract The dysfunction of a large number of genes participates in the pathogenesis of NSCLC. Liu and colleagues demonstrated that VPS33B acts as a tumor suppressor to halt NSCLC pathogenesis and elucidated the underlying mechanism by which VPS33B regulates c-Myc/p53/miR-192-3p to target CCNB1 via inactivating the Ras/ERK signal. |
| Databáze: | OpenAIRE |
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