Lnc-GAN1 expression is associated with good survival and suppresses tumor progression by sponging mir-26a-5p to activate PTEN signaling in non-small cell lung cancer
| Autor: | Zhe-Sheng Wen, Lan-Jun Zhang, Rui-Qi Wang, Shi-Juan Mai, Hui-Yun Wang, Fa-Zhong He, Dongni Chen, Xiaoran Long, Zhi-Lin Zhou, Mei-Yin Zhang, Ningning Zhou |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine PTEN Cancer Research Lung Neoplasms Mice Nude Biology Transfection lcsh:RC254-282 Mice Lnc-GAN1 03 medical and health sciences 0302 clinical medicine Carcinoma Non-Small-Cell Lung microRNA medicine Animals Humans Lung cancer Cell Proliferation Cell growth Research PTEN Phosphohydrolase miR-26a-5p Cell cycle lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Survival Analysis respiratory tract diseases MicroRNAs 030104 developmental biology Oncology Tumor progression 030220 oncology & carcinogenesis Disease Progression Cancer research biology.protein Female RNA Long Noncoding Ectopic expression Signal transduction Signal Transduction |
| Zdroj: | Journal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-19 (2021) Journal of Experimental & Clinical Cancer Research : CR |
| ISSN: | 1756-9966 |
| DOI: | 10.1186/s13046-020-01819-0 |
| Popis: | Background Long non-coding RNAs (lncRNAs) play vital roles in the development and progression of non-small-cell lung cancer (NSCLC); however, the role of most lncRNAs in NSCLC remains unknown. This study explored the clinical significance, biological function and underlying mechanism of lnc-GAN1 in NSCLC. Methods With a custom lncRNA microarray we found that lnc-GAN1 is markedly downregulated in NSCLC tissues. Then lnc-GAN1 expression level was measured using qRT-PCR in NSCLC tissues and cell lines. Survival was assessed using the Kaplan-Meier method. The biological functions of lnc-GAN1 in lung cancer cells were evaluated in vitro and in vivo. RNA fluorescence in situ hybridization and subcellular localization assays revealed the subcellular distribution of lnc-GAN1 in cells. Bioinformatic analysis was adopted to predict miRNAs and signaling pathways regulated by lnc-GAN1. RNA immunoprecipitation and Dual-luciferase reporter assays were used to assess the interaction between lnc-GAN1 and miR-26a-5p in lung cancer cells. Results lnc-GAN1 is downregulated in HCC tissues and associated with larger tumor size and poor overall survival and disease-free survival; its ectopic expression suppresses cell proliferation, colony formation, and cell cycle progression and induces apoptosis in NSCLC cells; it also inhibits tumor growth in the NSCLC xenograft model. We further proved that lnc-GAN1 is localized in cytoplasm and transcribed independently from its parental gene GAN. Mechanistically, lnc-GAN1 acts as a sponge for miR-26a-5p by two seed sequences, and the two non-coding RNAs have a negative relationship in NSCLC tissues; we further prove that PTEN is a direct target of miR-26a-5p and lnc-GAN1 inhibits cell cycle signaling pathway by activating PTEN, whose expression level correlated negatively with miR-26a-5p level but positively with lnc-GAN1 level in NSCLC samples. Conclusions Lnc-GAN1 is downregulated and associated with poor survival of NSCLC patients, and mechanistically acts as a tumor suppressor via sponging and inhibiting miR-26a-5p to upregulate PTEN. This study provides a potential prognostic biomarker and treatment target for NSCLC. |
| Databáze: | OpenAIRE |
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