Restoration of MiR17/20a in Solid Tumor Cells Enhances the Natural Killer Cell Antitumor Activity by Targeting Mekk2

Overview

Journal Cancer Immunol Res

Specialties Allergy & Immunology
Oncology

Date 2014 May 8

PMID 24801835

Citations 20

Authors

Hong Jiang

Ping Wang

Xiaohua Li

Qilong Wang

Zhong-Bin Deng

Xiaoying Zhuang

Jingyao Mu

Lifeng Zhang

Baomei Wang

Jun Yan

Donald Miller

Huang-Ge Zhang

Affiliations

Soon will be listed here.

Abstract

Aberrant microRNA (miRNA) expression has been identified in various human solid cancers. However, whether the levels of miRNA expression in tumor cells have any effect on tumor progression has not been determined. In this proof-of-concept study, the restoration of high-level expression of the miR17-92 cluster of miRNAs reveals its function as a tumor suppressor in murine solid cancer cells. Specifically, genetically engineered expression of higher levels of miR17/20a in the miR17-92 cluster in both murine breast cancer and colon cancer cells triggered natural killer (NK)-cell recognition by inhibiting the expression of MHC class I (H-2D) through the Mekk2-Mek5-Erk5 pathway. Results from the mouse tumor studies were recapitulated using samples of human solid tumors. Together, these data indicate that miR17/20a miRNAs function as tumor suppressors by reprogramming tumor cells for NK cell-mediated cytotoxicity.

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