MiR-506 Promotes Natural Killer Cell Cytotoxicity against Human Hepatocellular Carcinoma Cells by Targeting STAT3
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Purpose: It is well documented that natural killer (NK) cytotoxicity against hepatocellular carcinoma (HCC) cells is impaired inHCC, which might account for the failure of anti-tumor immune response. miRNAs are considered as important regulators forthe development and functions of NK cells. However, the entire role of miR-506 in NK cells remains far from being addressed. Materials and Methods: The expressions of miR-506 and signal transducer and activator of transcription 3 (STAT3) mRNA in primaryNK cells from HCC patients and healthy controls were detected by quantitative real-time PCR. NK cell cytotoxicity was assessedby CFSE/7AAD cytotoxicity assay and lactate dehydrogenase assay. Luciferase reporter assay, RNA immunoprecipitationassay, and western blot were conducted to confirm the interaction between miR-506 and STAT3. Results: miR-506 expression was downregulated and STAT3 mRNA was upregulated in primary NK cells from HCC patients. PrimaryNK cells from HCC patients showed remarkably reduced cytotoxicity against SMMC7721 or HepG2 cells. NK cell cytotoxicitywas positively correlated with miR-506 expression and negatively correlated with STAT3 mRNA expression. Additionally, miR-506 overexpression enhanced NK cell cytotoxicity against HCC cells, while miR-506 inhibitor showed the reverse effect. Moreover,miR-506 could suppress STAT3 expression by directly targeting 3'-untranslated regions of STAT3. A negative correlation betweenmiR-506 and STAT3 mRNA expression in HCC patients was observed. Mechanistically, overexpressing STAT3 greatly reversedmiR-506-mediated promotion of NK cell cytotoxicity against HCC cells. Conclusion: miR-506 enhanced NK cell cytotoxicity against HCC cells by targeting STAT3, suggesting that modulating miR-506expression maybe a promising approach for enhancing NK cell-based antitumor therapies.
Abstract
Purpose: It is well documented that natural killer (NK) cytotoxicity against hepatocellular carcinoma (HCC) cells is impaired inHCC, which might account for the failure of anti-tumor immune response. miRNAs are considered as important regulators forthe development and functions of NK cells. However, the entire role of miR-506 in NK cells remains far from being addressed. Materials and Methods: The expressions of miR-506 and signal transducer and activator of transcription 3 (STAT3) mRNA in primaryNK cells from HCC patients and healthy controls were detected by quantitative real-time PCR. NK cell cytotoxicity was assessedby CFSE/7AAD cytotoxicity assay and lactate dehydrogenase assay. Luciferase reporter assay, RNA immunoprecipitationassay, and western blot were conducted to confirm the interaction between miR-506 and STAT3. Results: miR-506 expression was downregulated and STAT3 mRNA was upregulated in primary NK cells from HCC patients. PrimaryNK cells from HCC patients showed remarkably reduced cytotoxicity against SMMC7721 or HepG2 cells. NK cell cytotoxicitywas positively correlated with miR-506 expression and negatively correlated with STAT3 mRNA expression. Additionally, miR-506 overexpression enhanced NK cell cytotoxicity against HCC cells, while miR-506 inhibitor showed the reverse effect. Moreover,miR-506 could suppress STAT3 expression by directly targeting 3'-untranslated regions of STAT3. A negative correlation betweenmiR-506 and STAT3 mRNA expression in HCC patients was observed. Mechanistically, overexpressing STAT3 greatly reversedmiR-506-mediated promotion of NK cell cytotoxicity against HCC cells. Conclusion: miR-506 enhanced NK cell cytotoxicity against HCC cells by targeting STAT3, suggesting that modulating miR-506expression maybe a promising approach for enhancing NK cell-based antitumor therapies.
참고문헌 (26)
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