Gastric Adenocarcinoma Predictive Long Intergenic Non-Coding RNA Promotes Tumor Occurrence and Progression in Non-Small Cell Lung Cancer via Regulation of the miR-661/eEF2K Signaling Pathway
| Autor: | Yukang Song, Haiting Gu, Junfeng Chen, Haiyan Shao |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Elongation Factor 2 Kinase
Male 0301 basic medicine Lung Neoplasms Cell cycle checkpoint Carcinogenesis Physiology Eukaryotic elongation factor-2 kinase (eEF2K) Mice Nude Pathogenesis Biology medicine.disease_cause Long non-coding RNAs (lncRNAs) lcsh:Physiology lcsh:Biochemistry 03 medical and health sciences 0302 clinical medicine Gastric adenocarcinoma predictive long intergenic non-coding RNA (GAPLINC) Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Animals Humans Gene silencing lcsh:QD415-436 Mice Inbred BALB C lcsh:QP1-981 Cell growth RNA Middle Aged Cell cycle Non-coding RNA miR-661 Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Disease Progression Cancer research Female RNA Long Noncoding Signal transduction Signal Transduction |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 51, Iss 5, Pp 2136-2147 (2018) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background/Aims: Long non-coding RNAs (lncRNAs) play vital roles in carcinogenesis as oncogenes or tumor suppressor genes. This study explored the biological function of lncRNA gastric adenocarcinoma predictive long intergenic non-coding RNA (GAPLINC) in human non-small cell lung cancer (NSCLC). Methods: GAPLINC expression in NSCLC specimens and cell lines was detected by qRT-PCR and Western blot. The effect of GAPLINC on cell proliferation was investigated using CCK8-assay, colony formation assay, and xenograft model. The effects of GAPLINC on apoptosis and cell cycle were determined using flow cytometry. The mechanism of GAPLINC involved in NSCLC was explored using Western blot, luciferase reporter assay, and RNA fluorescence in situ hybridization. Results: We found that GAPLINC expression was up-regulated in NSCLC tissues and cell lines. Overexpression of GAPLINC was associated with poor prognosis in patients with NSCLC. Silencing of GAPLINC significantly inhibited cell proliferation, promoted apoptosis, and induced cell cycle arrest in the G0/G1 phase. Results from xenograft transplantation showed that GAPLINC silencing inhibited the tumor growth in vivo. Interestingly, GAPLINC silencing decreased the expression of eukaryotic elongation factor-2 kinase (eEF2K) protein both in vivo and in vitro. Bioinformatic analysis and luciferase reporter confirmed that miR-661 targeted GAPLINC and eEF2K 3’-UTR and was negatively correlated with the expression of GAPLINC and eEF2K. Conclusion: Our findings indicate that GAPLINC promotes NSCLC tumorigenesis by regulating miR-661/eEF2K cascade and provide new insights for the pathogenesis underlying NSCLC and potential targets for therapeutic strategy. |
| Databáze: | OpenAIRE |
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