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Title 

Tumor suppressor microRNA-204-5p regulates growth, metastasis, and immune microenvironment remodeling in breast cancer

Authors 

B S HongH S RyuNamshin KimJ KimE LeeH MoonKyoung Hyoun KimM S JinN H KwonS KimD KimD H ChungK JeongK KimK Y KimH B LeeW HaJ YunJ I KimD Y NohH G Moon

Publisher 

American Association for Cancer Research

Issue Date 

2019

Citation 

Cancer Research

Abstract 

Various miRNAs play critical roles in the development and progression of solid tumors. In this study, we describe the role of miR-204-5p in limiting growth and progression of breast cancer. In breast cancer tissues, miR-204-5p was significantly downregulated compared with normal breast tissues, and its expression levels were associated with increased survival outcome in patients with breast cancer. Overexpression of miR-204-5p inhibited viability, proliferation, and migration capacity in human and murine breast cancer cells. In addition, miR-204-5p overexpression resulted in a significant alteration in metabolic properties of cancer cells and suppression of tumor growth and metastasis in mouse breast cancer models. The association between miR-204-5p expression and clinical outcomes of patients with breast cancer showed a nonlinear pattern that was reproduced in experimental assays of cancer cell behavior and metastatic capacities. Transcriptome and proteomic analysis revealed that various cancer-related pathways including PI3K/Akt and tumor? immune interactions were significantly associated with miR-204-5p expression. PIK3CB, a major regulator of PI3K/ Akt pathway, was a direct target for miR-204-5p, and the association between PIK3CB-related PI3K/Akt signaling and miR-204-5p was most evident in the basal subtype. The sensitivity of breast cancer cells to various anticancer drugs including PIK3CB inhibitors was significantly affected by miR-204-5p expression. In addition, miR-204-5p regulated expression of key cytokines in tumor cells and reprogrammed the immune microenvironment by shifting myeloid and lymphocyte populations. These data demonstrate both cellautonomous and non-cell?autonomous impacts of tumor suppressor miR-204-5p in breast cancer progression and metastasis.

URI 

https://doi.org/10.1158/0008-5472.CAN-18-0891

ISSN 

0008-5472

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-07-10


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