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LncRNA PINK1-AS promotes Gαi1-driven gastric cancer tumorigenesis by sponging microRNA-200a.
Lv, Yan; Wang, Yin; Song, Yu; Wang, Shu-Sheng; Cheng, Kai-Wen; Zhang, Zhi-Qing; Yao, Jin; Zhou, Li-Na; Ling, Zhuo-Yan; Cao, Cong.
Afiliação
  • Lv Y; Center of Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China.
  • Wang Y; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China.
  • Song Y; Department of Oncology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China.
  • Wang SS; Department of General Surgery, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China.
  • Cheng KW; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China.
  • Zhang ZQ; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China.
  • Yao J; The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China. dryaojin@yahoo.com.
  • Zhou LN; Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China. zhoulinaks@163.com.
  • Ling ZY; Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou, China. lingzhuoyan@126.com.
  • Cao C; Center of Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China. caocong@suda.edu.cn.
Oncogene ; 40(22): 3826-3844, 2021 06.
Article em En | MEDLINE | ID: mdl-33958720
ABSTRACT
Gastric cancer (GC) is one of the leading causes of human mortality around the world. We have previously shown that Gαi1 (the inhibitory subunit 1 of the heterotrimeric guanine nucleotide-binding protein) recruitment to ligand-activated receptor tyrosine kinases (RTKs) is essential for signaling. Testing its role in GC cancer-promoting functions, we found that Gαi1 is upregulated in human GC, correlating with poor overall survival. In established and primary human GC cells, Gαi1 shRNA (small hairpin RNA) or knockout produced significant anti-GC cell activity, proliferation and migration was inhibited, and apoptosis was activated. Conversely, ectopic Gαi1 overexpression promoted proliferation and migration of GC cells in vitro. By examining the tumor-suppressive miRNA microRNA-200a (miR-200a), we found that miR-200a directly silenced Gαi1 to induce anti-GC cell activity. The expression of miR-200a was downregulated in human GC, correlating with upregulation of a novel miR-200a-targeting long non-coding RNA (LncRNA), PINK1 (PTEN Induced Kinase 1)-AS. RNA immunoprecipitation, RNA-pull down, and RNA fluorescence in situ hybridization assays confirmed that PINK1-AS directly binds to miR-200a. Silencing PINK1-AS in GC cells led to miR-200a accumulation, Gαi1 downregulation, and inhibition of GC cell progression in vitro, whereas PINK1-AS upregulation produced the converse results. Significantly, anti-GC cell activity induced by PINK1-AS shRNA was ameliorated by the expression of miR-200a antisense or the 3'-UTR (untranslated region)-depleted Gαi1. In vivo, the growth of subcutaneous MGC-803 xenografts in nude mice was inhibited by PINK1-AS shRNA, but accelerated by PINK1-AS overexpression. Patient-derived GC xenograft growth in nude mice was largely inhibited after intratumoral injection of PINK1-AS shRNA lentivirus. In conclusion, PINK1-AS promotes Gαi1-driven GC progression by sponging miR-200a.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP / MicroRNAs / RNA Longo não Codificante Limite: Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP / MicroRNAs / RNA Longo não Codificante Limite: Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2021 Tipo de documento: Article