Mining of potential microRNAs with clinical correlation - regulation of syndecan-1 expression by miR-122-5p altered mobility of breast cancer cells and possible correlation with liver injury
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YihHuei Uen1,2,3, Jin-Wun Wang4, ChiaChen Wang5,6, Yaoyun Jhang5, Jo-Yun Chung5, TingTing Tseng5, MingJen Sheu7 and ShaoChen Lee5
1Department of Surgery, ChiMei Hospital, Chiali, Jiali Dist., Tainan City, Taiwan
2Department of Surgery, Asia University Hospital, Taichung City, Taiwan
3Department of Biotechnology, Asia University, Taichung City, Taiwan
4Department of Surgery, ChiMei Hospital, Chiali, Jiali Dist., Tainan City, Taiwan
5School of Medicine, Fu Jen Catholic University, Xinzhuang Dist., New Taipei City, Taiwan
6Department of Dermatology, Cardinal Tien Hospital, Xindian Dist., New Taipei City, Taiwan
7Department of Hepato-Gastroenterology, ChiMei Hospital, Yongkang Dist., Tainan City, Taiwan
ShaoChen Lee, email: [email protected]
Keywords: microRNA; syndecan-1; breast cancer; exosome
Received: November 14, 2016 Accepted: May 24, 2018 Published: June 15, 2018
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.
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