MiR-214 promotes the antitumor effect of NK cells in colorectal cancer liver metastasis through USP27X/Bim

Jinlan He; Zhe Qing; Yifei Li; Jie Lin; Dan Wang; Wanggang Xu; Xiyuan Chen; Xiangyu Meng; Jian Duan

doi:10.1007/s10616-024-00642-1

MiR-214 promotes the antitumor effect of NK cells in colorectal cancer liver metastasis through USP27X/Bim

Cytotechnology. 2024 Dec;76(6):667-681. doi: 10.1007/s10616-024-00642-1. Epub 2024 Jun 28.

Authors

Jinlan He^#¹, Zhe Qing^#¹, Yifei Li², Jie Lin², Dan Wang², Wanggang Xu², Xiyuan Chen³, Xiangyu Meng⁴, Jian Duan¹

Affiliations

¹ Department of General Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, 650000 Yunnan China.
² Department of Organ Transplantation, The First Affiliated Hospital of Kunming Medical University, Kunming, 650000 Yunnan China.
³ Department of Hepatological Surgery, The Third People's Hospital of Honghe Hani and Yi Autonomous Prefecture, Gejiu, 661000 Yunnan China.
⁴ Department of Hepatological Surgery, Peace Hospital Affiliated to Changzhi Medical College, Changzhi, 046000 Shanxi China.

^# Contributed equally.

PMID: 39435421
PMCID: PMC11490475 (available on 2025-12-01)
DOI: 10.1007/s10616-024-00642-1

Abstract

Colorectal cancer (CRC) is a common tumor type, and liver metastasis reduces the long-term survival in CRC patients. Natural killer (NK) cells play an important role in anti-tumor immunity. The aim of this study was to investigate the mechanism of miR-214-5p on NK cells in CRC liver metastasis. We collected clinical samples of CRC liver metastasis and nonmetastatic tissues and purchased the human NK cell lines NK92 and liver metastatic CRC cells KM12L4 for research. RT‒qPCR, Western blot, CCK-8, Transwell, and flow cytometry methods were used to evaluate the effect of miR-214-5p/USP27X/Bim pathway regulating NK cell activity on CRC liver metastasis. In addition, we also investigated the potential targets and regulatory mechanisms of the signaling pathway of miR-214-5p. In this study, we found that miR-214-5p was downregulated in CRC liver metastasis tissues. After transfection of miR-214-5p mimic, the activity of NK cells was significantly enhanced, and the proliferation and migration ability of CRC liver metastasis cells were inhibited, while inducing tumor cell apoptosis. Further research proved that USP27X is a potential target for miR-214-5p and upregulates Bim level through deubiquitination. In addition, miR-214-5p mimic reduced the level of USP27X and Bim, thereby enhancing the antitumor effect of NK cells. In conclusion, our research results show that miR-214-5p promotes the antitumor effect of NK cells by regulating the USP27X/Bim pathway, thereby inhibiting CRC liver metastasis. This finding reveals the important role of miR-214-5p in regulating the immune function of NK cells, and provides new ideas for developing new immunotherapy strategies.

Supplementary information: The online version contains supplementary material available at 10.1007/s10616-024-00642-1.

Keywords: Colorectal cancer with liver metastasis; NK cells; USP27X/Bim; miR-214-5p.

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