title: MiR-199a/b-3p suppresses migration and invasion of breast cancer cells by downregulating PAK4/MEK/ERK signaling pathway.
abstract: MicroRNA-199a/b-3p is downregulated in several types of aggressive cancer, and its decrement significantly correlates with poor survival. Here, we aim to investigate the biological function of miR-199a/b-3p and its regulation of target genes in breast cancer cells with highly metastatic potential. In addition, we found that miR-199a/b-3p expression was much lower in MDA-MB-231, CAL120, and HCC1395 breast cancer cells with highly metastatic potential. Functional assays showed that restored miR-199a/b-3p expression inhibited MDA-MB-231 cell growth, cell-cycle progression, migration, and invasion. In addition, we experimentally demonstrated that PAK4 was the direct target of miR-199a/b-3p, hypo-expression of PAK4 suppressed proliferation, migration and invasion of MDA-MB-231 cells, and overexpression of PAK4 significantly rescued the inhibitory effect of miR-199a/b-3p on MDA-MB-231 cell growth, migration, and invasion. Further, we also observed that miR-199a/b-3p could inactivate the PAK4/MEK/ERK signaling pathway. Thus, miR-199a/b-3p functions as a tumor suppressor and has an important role in breast cancer metastasis through PAK4/MEK/ERK signaling pathway.
authors.affiliation: Laboratory Center, The First Hospital of Jilin University, Changchun, China.|Tumor Biotherapy Center, Jilin Province People's Hospital, Changchun, China.
authors.forename: Shou-Qing
authors.initials: SQ
authors.lastname: Li
authors.affiliation: Medical College, Yanbian University, Yanbian, China.
authors.forename: Zi-Hang
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Tumor Biotherapy Center, Jilin Province People's Hospital, Changchun, China.
authors.forename: Xu-Guang
authors.initials: XG
authors.lastname: Mi
authors.affiliation: Tumor Biotherapy Center, Jilin Province People's Hospital, Changchun, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Laboratory Center, The First Hospital of Jilin University, Changchun, China.|Tumor Biotherapy Center, Jilin Province People's Hospital, Changchun, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tan
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D035683:MicroRNAs / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C531408:mirn199 microRNA, human; C116367:PAK4 protein, human; D054462:p21-Activated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: PAK4; breast cancer; cancer metastasis; miR-199a/b-3p