Fatty acid synthase is a primary target of MiR-15a and MiR-16-1 in breast cancer
| Autor: | Jinming Shi, Meimei Wan, Paul Cao, Qiang Zhang, Qingyuan Zhang, Yunxuan Wang, Jingxuan Wang, Guangchao Sui, Xiao Zhang, Wennuan Liu, Steven J. Kridel, Jianfeng Xu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Time Factors Down-Regulation Breast Neoplasms 3′-UTR Transfection Bioinformatics medicine.disease_cause Gene Expression Regulation Enzymologic 03 medical and health sciences breast cancer 0302 clinical medicine Breast cancer Gene expression microRNA Humans Medicine Fatty acid synthase (FASN) 3' Untranslated Regions Cell Proliferation Binding Sites biology business.industry Three prime untranslated region Cancer medicine.disease 3. Good health Fatty Acid Synthase Type I Gene Expression Regulation Neoplastic MicroRNAs Fatty acid synthase 030104 developmental biology miR-15a and miR-16-1 Oncology 030220 oncology & carcinogenesis MCF-7 Cells gene expression biology.protein Cancer research Female Ectopic expression business Carcinogenesis Signal Transduction Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Jingxuan Wang 1, 3 , Xiao Zhang 2 , Jinming Shi 2 , Paul Cao 3 , Meimei Wan 3 , Qiang Zhang 3 , Yunxuan Wang 1 , Steven J. Kridel 3 , Wennuan Liu 4 , Jianfeng Xu 3, 4 , Qingyuan Zhang 1 , Guangchao Sui 2, 3 1 Department of Medical Oncology, the Third Affiliated Hospital of Harbin Medical University, Harbin P. R. China 2 College of Life Science, Northeast Forestry University, Harbin, China 3 Department of Cancer Biology and Comprehensive Cancer Center 4 Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem Correspondence to: Qingyuan Zhang, email: zhma19650210@163.com Guangchao Sui, email: gsui@wakehealth.edu , gcsui@nefu.edu.cn Keywords: Fatty acid synthase (FASN), miR-15a and miR-16-1, 3’-UTR, breast cancer, gene expression Received: December 13, 2015 Accepted: September 26, 2016 Published: October 05, 2016 ABSTRACT Fatty acid synthase (FASN) is upregulated in breast cancer and correlates with poor prognosis. FASN contributes to mammary oncogenesis and serves as a bona fide target in cancer therapies. MicroRNAs inhibit gene expression through blocking mRNA translation or promoting mRNA degradation by targeting their 3’-UTRs. We identified four microRNAs in two microRNA clusters miR-15a-16-1 and miR-497-195 that share a common seed sequence to target the 3′-UTR of the FASN mRNA. In reporter assays, both of these microRNA clusters inhibited the expression of a reporter construct containing the FASN 3’-UTR. However, only ectopic miR-15a-16-1, but not miR-497-195, markedly reduced the levels of endogenous FASN in breast cancer cells. Both miR-15a and miR-16-1 contributes to inhibiting FASN expression and breast cancer cell proliferation. Consistently, a sponge construct consisting of eight repeats of the FASN 3’-UTR region targeted by these microRNAs could markedly increase endogenous FASN levels in mammary cells. When FASN expression was restored by ectopic expression in breast cancer cells, retarded cell proliferation caused by miR-15a-16-1 was partially rescued. In conclusion, we demonstrated that FASN expression is primarily downregulated by miR-15a and miR-16-1 in mammary cells and FASN is one of the major targets of these two tumor suppressive microRNAs. |
| Databáze: | OpenAIRE |
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