Abstract
MicroRNAs are small noncoding RNAs acting as novel biomarkers of various diseases and potential regulators of protein expression and functions. Syndecan-1 is the heparan sulfate proteoglycan associated with malignancy of various cancers, including breast cancer. In this study, we proposed a experimental workflow to investigate potential microRNAs that regulate SDC1 expression and affect breast cancer cell mobility.MicroRNA candidates were selected from available Gene Expression Omnibus datasets on breast malignancy. Further in silico duplex hybridization and multiplex PCR approach were used to screen potential microRNAs. Analysis showed increased syndecan-1 expression but decreased miR-122-5p level upon breast malignancy. Western blot and in vitro luciferase assay confirmed the targeting of 3′-untranslated region of syndecan-1 and suppression of syndecan-1 expression by miR-122-5p. The suppression of syndecan-1 expression by miR-122-5p or shRNAs against syndecan-1 increased breast cancer cell mobility; while overexpression of syndecan-1 inhibited cell mobility. In further, miR-122-5p was enriched in liver cell-derived exosomes that was able to suppress syndecan-1 expression and increase cell mobility in breast cancer cells.In conclusion, our results suggested the downregulation of SDC1 by miR-122-5p or liver-cell-derived exosomes would enhance breast cancer cell mobility. Metastasis or mobility of breast cancer cells might be affected by circulating miR-122-5p and not directly correlated with progression of breast cancer.
Highlights
Syndecan-1 (SDC1) is a heparan sulfate proteoglycan that acts as a binding acceptor for many soluble growth factors, cytokines, chemokines, and membrane-bound receptors [1]
SDC1 was demonstrated to be highly expressed in patients with malignant breast cancer, which was correlated with poor prognoses and aggressive phenotypes [6, 16]
We had demonstrated that miR-122-5p suppressed SDC1 expression and enhanced the mobility of MCF-7 breast cancer cells, we examined whether liverderived exosomes containing miR-122-5p would affect the mobility of breast cancer cells
Summary
Syndecan-1 (SDC1) is a heparan sulfate proteoglycan that acts as a binding acceptor for many soluble growth factors, cytokines, chemokines, and membrane-bound receptors [1]. SDC-1 regulates cellular activity through cell signaling associated with cell proliferation, differentiation, and cell–matrix interaction [2,3,4]. Increased levels of SDC1 are associated with the malignancy of various cancers [5], including breast cancer [6, 7]. SDC1 expression was decreased or increased in various tumor types and associated with histologic grades or malignancy. Higher SDC1 expression was associated with higher histologic grade and inversely related to hormonal receptor status of breast cancer cells [8]. Several literatures implied that distant metastasis of breast cancer would correlate with www.oncotarget.com acute liver failure [9, 10]. No possible mechanism was proposed to explain the liver-specific metastasis
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