miR-24 inhibited the killing effect of natural killer cells to colorectal cancer cells by downregulating Paxillin

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Ling-li Zhang, Lian-feng Zhang, Yun-bo Shi
ObjectiveTo identify the molecular mechanism that modulates the killing effect of natural killer (NK) cells to colorectal cancer cells.Materials and methods: Expressions of miR-24 and Paxillin were detected by qRT-PCR and Western blot. Secretions of IFN-γ and TNF-α were measured by ELISA. The killing effect of NK cells was detected by CytoTox 96 non-radioactive cytotoxicity assay. Luciferase reporter assay was conducted to confirm the regulation of miR-24 on Paxillin.ResultsmiR-24 was overexpressed in NK cells from patients with colorectal cancer than healthy volunteers. Secretions of IFN-γ and TNF-α in activated NK cells were significantly increased, indicating the enhancement of the killing effect of NK cells. Paxillin expression was overexpressed in activated NK cells. Interference of Paxillin significantly decreased Paxillin expression, secretions of IFN-γ and TNF-α, and the killing effect of NK cells to colorectal cancer cells. In addition, we confirmed that Paxillin was a direct target of miR-24, and miR-24 was negatively correlated with Paxillin. Moreover, overexpression of miR-24 inhibited secretions of IFN-γ and TNF-α, and decreased cytotoxicity by downregulating Paxillin expression. Finally, we observed that overexpression of Paxillin significantly decreased tumor volume of colorectal cancer.ConclusionOverexpression of miR-24 supressed the killing effect of NK cells to colorectal cancer cells by downregulating Paxillin expression.



http://ift.tt/2EXffqQ