title: Fatty acid synthase is a primary target of MiR-15a and MiR-16-1 in breast cancer.
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.
authors.affiliation: Department of Medical Oncology, the Third Affiliated Hospital of Harbin Medical University, Harbin P. R. China.|Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Life Science, Northeast Forestry University, Harbin, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Life Science, Northeast Forestry University, Harbin, China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Cao
authors.affiliation: Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Meimei
authors.initials: M
authors.lastname: Wan
authors.affiliation: Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin P. R. China.
authors.forename: Yunxuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kridel
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Wennuan
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.|Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin P. R. China.
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: College of Life Science, Northeast Forestry University, Harbin, China.|Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Guangchao
authors.initials: G
authors.lastname: Sui
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D015536:Down-Regulation; D054890:Fatty Acid Synthase, Type I / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I
keywords: 3’-UTR; Fatty acid synthase (FASN); breast cancer; gene expression; miR-15a and miR-16-1