title: Suppressive role of miR-502-5p in breast cancer via downregulation of TRAF2.
abstract: TRAF2 promotes cancer cell survival, proliferation and metastasis through the NF-κB pathway by directly interacting with various TNF recepors. However, the molecular mechanism of TRAF2 dysregulation in breast cancer remains to be elucidated. In the present study, miR-502-5p was predicted as a potential regulator of TRAF2. miR-502-5p was significantly downregulated in breast cancer tissues when compared to the level in paired normal breast tissues. The breast cancer cell lines including MCF-7 and MDA-MB-231 expressed a lower level of miR-502-5p when compared to the level in the non-malignant breast epithelial cell line MCF-10A. In vitro, miR-502-5p enhanced early apoptosis and inhibited proliferation of breast cancer cells. Luciferase reporter assay results showed that miR-502-5p could bind to the 3'-untranslated region of the TRAF2 gene, thus, exerting an inhibitory effect on TRAF2. Furthermore, silencing of TRAF2 exhibited effects similar to those of exogenous miR‑502-5p, while overexpression of TRAF2 partially abrogated miR-502-5p-mediated suppression in breast cancer cells. In conclusion, miR-502-5p may act as a tumor-suppressor gene by targeting oncogenic TRAF2 in breast cancer and, therefore, may be a potential diagnostic and anticancer therapeutic marker for breast cancer.
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Sun
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Zhi-Juan
authors.initials: ZJ
authors.lastname: Zhao
authors.affiliation: Department of Pancreatic Surgery, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Ai-Lian
authors.initials: AL
authors.lastname: Wang
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Hua-Yan
authors.initials: HY
authors.lastname: Ren
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Ke-Xin
authors.initials: KX
authors.lastname: Diao
authors.affiliation: Department of Medical Genetics, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Wei-Neng
authors.initials: WN
authors.lastname: Fu
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: En-Hua
authors.initials: EH
authors.lastname: Wan
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Mi
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B; D009362:Neoplasm Metastasis / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D047992:TNF Receptor-Associated Factor 2 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C545730:MIRN502 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D034741:RNA, Small Interfering; D047992:TNF Receptor-Associated Factor 2