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Breast Cancer Research
Published in: Breast Cancer Research 1/2021

01-12-2021 | Breast Cancer | Research article

MicroRNA-3613-3p functions as a tumor suppressor and represents a novel therapeutic target in breast cancer

Authors: Chong Chen, Yundi Pan, Lipeng Bai, Huilin Chen, Zhaojun Duan, Qin Si, Ruizhe Zhu, Tsung-Hsien Chuang, Yunping Luo

Published in: Breast Cancer Research | Issue 1/2021

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Abstract

Background

MicroRNAs have been reported to participate in tumorigenesis, treatment resistance, and tumor metastasis. Novel microRNAs need to be identified and investigated to guide the clinical prognosis or therapy for breast cancer.

Method

The copy number variations (CNVs) of MIR3613 from Cancer Genome Atlas (TCGA) or Cancer Cell Line Encyclopedia (CCLE) were analyzed, and its correlation with breast cancer subtypes or prognosis was investigated. The expression level of miR-3613-3p in tumor tissues or serum of breast cancer patients was detected using in situ hybridization and qPCR. Gain-of-function studies were performed to determine the regulatory role of miR-3613-3p on proliferation, apoptosis, and tumor sphere formation of human breast cancer cells MDA-MB-231 or MCF-7. The effects of miR-3613-3p on tumor growth or metastasis in an immunocompromised mouse model of MDA-MB-231-luciferase were explored by intratumor injection of miR-3613-3p analogue. The target genes, interactive lncRNAs, and related signaling pathways of miR-3613-3p were identified by bioinformatic prediction and 3′-UTR assays.

Results

We found that MIR3613 was frequently deleted in breast cancer genome and its deletion was correlated with the molecular typing, and an unfavorable prognosis in estrogen receptor-positive patients. MiR-3613-3p level was also dramatically lower in tumor tissues or serum of breast cancer patients. Gain-of-function studies revealed that miR-3613-3p could suppress proliferation and sphere formation and promote apoptosis in vitro and impeded tumor growth and metastasis in vivo. Additionally, miR-3613-3p might regulate cell cycle by targeting SMS, PAFAH1B2, or PDK3 to restrain tumor progression.

Conclusion

Our findings indicate a suppressive role of miR-3613-3p in breast cancer progression, which may provide an innovative marker or treatment for breast cancer patients.
Appendix
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Metadata
Title
MicroRNA-3613-3p functions as a tumor suppressor and represents a novel therapeutic target in breast cancer
Authors
Chong Chen
Yundi Pan
Lipeng Bai
Huilin Chen
Zhaojun Duan
Qin Si
Ruizhe Zhu
Tsung-Hsien Chuang
Yunping Luo
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2021
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-021-01389-9

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