Abstract
BackgroundMicroRNAs 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.MethodThe 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.ResultsWe 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.ConclusionOur 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.
Highlights
Breast cancer is the most common cancer and the second cause of cancer-related death in women [1]
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
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
Summary
Breast cancer is the most common cancer and the second cause of cancer-related death in women [1]. Improved treatments with combination of surgery, radiotherapy, and chemotherapy have increased the overall survival rate for breast cancer patients, but some patients still undergo tumor relapse, metastasis, or therapy resistance. Cancer stem cells (CSCs) possess a potent capacity for self-renewal and differentiation and, are responsible for the unrestricted growth of tumors [3]. Treatments targeting CSCs may be a more effective strategy to eliminate the source of tumor growth, leading to considerable clinical benefit. It is important to identify specific miRNAs associated with the tumor subtype when developing miRNA-targeted therapeutics. 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
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