MiR-218-5p Suppresses the Killing Effect of Natural Killer Cell to Lung Adenocarcinoma by Targeting SHMT1
| Autor: | Dian-Dian Chen, Yi-Li Hu, Xiaofei Tang, Li-Hua Dong, Jingjing Li, Quan-Jun Yang, Lili Yu |
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| Rok vydání: | 2019 |
| Předmět: |
Lung adenocarcinoma
Male miR-218-5p Mice Nude Adenocarcinoma of Lung Apoptosis 030204 cardiovascular system & hematology Cell Line Natural killer cell 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Lactate dehydrogenase medicine Animals Humans Luciferase Secretion Cytotoxicity Cell Proliferation Glycine Hydroxymethyltransferase Mice Inbred BALB C natural killer cells Base Sequence Chemistry General Medicine SHMT1 Gene Expression Regulation Neoplastic Killer Cells Natural Blot MicroRNAs medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Cytokines Original Article Tumor necrosis factor alpha |
| Zdroj: | Yonsei Medical Journal |
| ISSN: | 1976-2437 0513-5796 |
| Popis: | Purpose Lung adenocarcinoma (LA) is one of the major types of lung cancer. MicroRNAs (miRNAs) play an essential role in regulating responses of natural killer (NK) cells to cancer malignancy. However, the mechanism of miR-218-5p involved in the killing effect of NK cells to LA cells remains poorly understood. Materials and methods The expression of miR-218-5p was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Serine hydroxymethyl transferase 1 (SHMT1) level was detected by qRT-PCR or western blots. Cytokines production of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by ELISA. The killing effect of NK cells to LA cells was investigated using lactate dehydrogenase cytotoxicity assay kit. The interaction of miR-218-5p and SHMT1 was probed by luciferase activity assay. Xenograft model was established to investigate the killing effect of NK cells in vivo. Results miR-218-5p was enhanced and SHMT1 was inhibited in NK cells of LA patients, whereas stimulation of interleukin-2 (IL-2) reversed their abundances. Addition of miR-218-5p reduced IL-2-induced cytokines expression and cytotoxicity in NK-92 against LA cells. Moreover, SHMT1 was negatively regulated by miR-218-5p and attenuated miR-218-5p-mediated effect on cytotoxicity, IFN-γ and TNF-α secretion in IL-2-activated NK cells. In addition, miR-218-5p exhaustion inhibited tumor growth by promoting killing effect of NK cells. Conclusion miR-218-5p suppresses the killing effect of NK cells to LA cells by targeting SHMT1, providing a potential target for LA treatment by ameliorating NK cells function. |
| Databáze: | OpenAIRE |
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