title: RNA-Binding Protein Dnd1 Promotes Breast Cancer Apoptosis by Stabilizing the Bim mRNA in a miR-221 Binding Site.
abstract: RNA-binding proteins (RBPs) and miRNAs are capable of controlling processes in normal development and cancer. Both of them could determine RNA transcripts fate from synthesis to decay. One such RBP, Dead end (Dnd1), is essential for regulating germ-cell viability and suppresses the germ-cell tumors development, yet how it exerts its functions in breast cancer has remained unresolved. The level of Dnd1 was detected in 21 cancerous tissues paired with neighboring normal tissues by qRT-PCR. We further annotated TCGA (The Cancer Genome Atlas) mRNA expression profiles and found that the expression of Dnd1 and Bim is positively correlated (p= 0.04). Patients with higher Dnd1 expression level had longer overall survival (p= 0.0014) by KM Plotter tool. Dnd1 knockdown in MCF-7 cells decreased Bim expression levels and inhibited apoptosis. While knockdown of Dnd1 promoted the decay of Bim mRNA 3'UTR, the stability of Bim-5'UTR was not affected. In addition, mutation of miR-221-binding site in Bim-3'UTR canceled the effect of Dnd1 on Bim mRNA. Knockdown of Dnd1 in MCF-7 cells confirmed that Dnd1 antagonized miR-221-inhibitory effects on Bim expression. Overall, our findings indicate that Dnd1 facilitates apoptosis by increasing the expression of Bim via its competitive combining with miR-221 in Bim-3'UTR. The new function of Dnd1 may contribute to a vital role in breast cancer development.
authors.affiliation: Department of Thyroid-Breast Surgery, Lishui Municipal Central Hospital, Lishui Hospital of Zhejiang University, The 5th Affiliated Hospital of Wenzhou Medical University, Zhejiang 323000, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Cheng
authors.affiliation: Department of Thyroid-Breast Surgery, Lishui Municipal Central Hospital, Lishui Hospital of Zhejiang University, The 5th Affiliated Hospital of Wenzhou Medical University, Zhejiang 323000, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Oncology Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Lu
authors.affiliation: Department of Thyroid-Breast Surgery, Lishui Municipal Central Hospital, Lishui Hospital of Zhejiang University, The 5th Affiliated Hospital of Wenzhou Medical University, Zhejiang 323000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Thyroid-Breast Surgery, Lishui Municipal Central Hospital, Lishui Hospital of Zhejiang University, The 5th Affiliated Hospital of Wenzhou Medical University, Zhejiang 323000, China.
authors.forename: Shuzheng
authors.identifier: 0000-0002-0084-6001
authors.initials: S
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics*; D000072224:Bcl-2-Like Protein 11 / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000072224:Bcl-2-Like Protein 11; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C528453:Dnd1 protein, human; C525709:MIR221, human