Abstract
In this study, we evaluated the function and regulation of the long non-coding RNA (lncRNA) FAM83H-AS1 in triple-negative breast cancer (TNBC). Our data show that the FAM83H-AS1 levels are increased in human TNBC cells and tissues. Proliferation, migration, and invasion of TNBC cells are decreased by FAM83H-AS1 suppression, but increased by FAM83H-AS1 overexpression. Bioinformatics analysis revealed that miR-136-5p is a potential target of FAM83H-AS1. MiR-136-5p expression is decreased in TNBC tissues, and its overexpression suppresses TNBC cell proliferation, migration, and invasion. MiR-136-5p suppression reverses the FAM83H-AS1 silencing-mediated inhibition of TNBC cell proliferation, migration, and invasion, suggesting that FAM83H-AS1 exerts its oncogenic effect by inhibiting miR-136-5p. Our data identify metadherin (MTDH) as the target gene of miR-136-5p, and demonstrate that the MTDH expression is increased in human TNBC tissues, which induces proliferation, migration, and invasion of TNBC cells. Importantly, our in vivo data show that FAM83H-AS1 also promotes tumor growth in TNBC mouse xenografts. Together, our results demonstrate that FAM83H-AS1 functions as an oncogenic lncRNA that regulates miR-136-5p and MTDH expression during TNBC progression, and suggest that targeting the FAM83H-AS1/miR-136-5p/MTDH axis may serve as a novel therapeutic target in TNBC.
Highlights
Triple-negative breast cancer (TNBC) cells lack expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2)
Our results demonstrate that FAM83H-AS1 functions as an oncogenic Long noncoding RNAs (lncRNAs) that regulates miR-136-5p and MTDH expression during triple-negative breast cancer (TNBC) progression, and suggest that targeting the FAM83H-AS1/miR-136-5p/MTDH axis may serve as a novel therapeutic target in TNBC
Our results demonstrate that the expression of FAM83H-AS1 is increased in TNBC cells and tissues, and promotes TNBC cell proliferation, migration, and invasion by regulating miR-136-5p and metadherin (MTDH) expression
Summary
Triple-negative breast cancer (TNBC) cells lack expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). TNBC accounts for approximately 15% of invasive breast cancers, and is the most aggressive breast cancer subtype with a poor prognosis. Conventional chemotherapy remains the standard of care for patients with advanced TNBC [1, 2]. It is www.aging-us.com imperative to identify the underlying mechanisms, and develop diagnostic and prognostic biomarkers for TNBC treatment. Dysregulation of lncRNAs has been implicated in cancer cell proliferation, invasion, and metastasis [8,9,10]. Elevated lncRNA TTTY15 promotes prostate cancer progression through targeting miRNA let-7 [12], while lncRNA n384546 promotes thyroid papillary cancer cell proliferation, invasion, and migration by regulating miR-1455p /AKT3 signaling [13]
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