title: MicroRNA-133b is a key promoter of cervical carcinoma development through the activation of the ERK and AKT1 pathways.
abstract: We report that elevated microRNA-133b (miR-133b) acts as an oncogene in human cervical carcinoma to promote tumorigenesis and metastasis. In situ hybridization confirmed that miR-133b is localized in proliferating human cervical carcinoma cells with levels progressively elevating throughout advancing stages. Cellular studies showed that miR-133b enhances cell proliferation and colony formation by targeting mammalian sterile 20-like kinase 2 (MST2), cell division control protein 42 homolog (CDC42) and ras homolog gene family member A (RHOA), which subsequently results in activation of the tumorigenic protein kinase B alpha (AKT1) and mitogen-activated protein kinase (ERK1 and ERK2, here abbreviated as ERK) signaling pathways. Mouse experiments revealed that upregulation of miR-133b in cervical carcinoma cells strongly promotes both in vivo tumorigenesis and independent metastasis to the mouse lung. The data indicates that upregulation of miR-133b shortens the latency of cervical carcinoma. Together, these findings suggest that miR-133b could be a potent marker for the early onset of cervical carcinoma.
authors.affiliation: Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Qin
authors.forename: P
authors.initials: P
authors.lastname: Dong
authors.forename: C
authors.initials: C
authors.lastname: Ma
authors.forename: K
authors.initials: K
authors.lastname: Mitchelson
authors.forename: T
authors.initials: T
authors.lastname: Deng
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: X
authors.initials: X
authors.lastname: Feng
authors.forename: Y
authors.initials: Y
authors.lastname: Ding
authors.forename: X
authors.initials: X
authors.lastname: Lu
authors.forename: J
authors.initials: J
authors.lastname: He
authors.forename: H
authors.initials: H
authors.lastname: Wen
authors.forename: J
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001483:Base Sequence; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D000090742:Serine-Threonine Kinase 3; D014158:Transcription, Genetic; D047368:Tumor Burden; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D000099317:Hippo Kinases
chemical_list: D035683:MicroRNAs; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000090742:Serine-Threonine Kinase 3; D020764:cdc42 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; C548234:MIRN133 microRNA, human; C066737:RHOA protein, human; C494918:AKT1 protein, human; C097835:STK3 protein, human; D000099317:Hippo Kinases