title: Regulation of cancerous progression and epithelial-mesenchymal transition by miR-34c-3p via modulation of MAP3K2 signaling in triple-negative breast cancer cells.
abstract: Emerging but limited data have evidenced an essential involvement of microRNAs (miRNAs) in the development and progression of triple negative breast cancer (TNBC), which empowers these small regulators as an innovative therapeutic approach, especially for this unique tumor subgroup still lacking an efficient and specific therapeutic target. Herein, we reported the down-regulation of miR-34c-3p level in TNBC tissues, and its expression was closely associated with estrogen receptor alpha (ERα), but not other receptors, in well-characterized breast cancer (BCa) cells. Functionally, ectopic expression of miR-34c-3p inhibited migration, invasion and epithelial-mesenchymal transition (EMT) in TNBC cells. From a mechanistic standpoint, bioinformatics coupled with luciferase and gain-of-function, loss-of-function assays showed that miR-34c-3p may regulate TNBC progression by directly targeting the 3'-untranslated region (UTR) of mitogen-activated protein kinase kinase kinase 2 (MAP3K2). Consistently, MAP3K2 overexpression could effectively rescue miR-34c-3p mimics-induced suppression of cell invasion and EMT. In light of these findings, miR-34c-3p may function as a tumor suppressor in regulating of TNBC invasiveness and EMT through negatively modulating MAP3K2 pathway. Future endeavor in this field may help to identify a novel biomarker to predict prognosis and response to therapy in TNBC.
authors.affiliation: Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Ultrasound, Xianyang Central Hospital, Xianyang 712000, China.
authors.forename: Wei-Zhi
authors.initials: WZ
authors.lastname: Li
authors.affiliation: Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Huang
authors.affiliation: Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Wei
authors.affiliation: Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Nan-Lin
authors.initials: NL
authors.lastname: Li
authors.affiliation: Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: lingrui0105@163.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Ling
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048730:MAP Kinase Kinase Kinase 2; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D048730:MAP Kinase Kinase Kinase 2; D020930:MAP Kinase Kinase Kinases; C482618:MAP3K2 protein, human
keywords: Epithelial-mesenchymal transition (EMT); Estrogen receptor alpha (ERα); MAP3K2; Triple negative breast cancer (TNBC); miR-34c-3p