title: MiR-29c suppresses invasion and metastasis by targeting TIAM1 in nasopharyngeal carcinoma.
abstract: Based on microarray analysis, we previously reported that miR-29c is significantly downregulated in nasopharyngeal carcinoma (NPC). However, little is known about the effect and molecular mechanisms of action of miR-29c deregulation during the development and progression of NPC. Quantitative RT-PCR demonstrated that miR-29c was significantly downregulated in NPC cell lines and clinical specimens. Wound healing, Transwell migration and lung metastasis assays demonstrated that ectopic expression of miR-29c inhibited NPC cell migration and invasion in vitro and suppressed the formation of lung metastases in vivo. T cell lymphoma invasion and metastasis 1 (TIAM1) was confirmed as a miR-29c target gene using luciferase reporter assays, quantitative RT-PCR and Western blotting. Ectopic expression of TIAM1 significantly promoted the migration and invasion of SUNE-1 cell line stably overexpressing miR-29c. The prognostic value of TIAM1 was analyzed in 217 NPC patients using immunohistochemistry. Strikingly, patients with high TIAM1 expression had poorer overall, disease-free and distant metastasis-free survival than patients with low TIAM1 expression. Furthermore, multivariate Cox regression analysis revealed that TIAM1 could serve as an independent prognostic factor in NPC. The newly identified miR-29c/TIAM1 pathway further elucidates the molecular mechanisms regulating invasion and metastasis in NPC, and may provide novel prognostic and treatment strategies for NPC patients.
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Ling-Long
authors.initials: LL
authors.lastname: Tang
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Rui-Xue
authors.initials: RX
authors.lastname: Cui
authors.forename: Hui-Yun
authors.initials: HY
authors.lastname: Wang
authors.forename: Bi-Jun
authors.initials: BJ
authors.lastname: Huang
authors.forename: Qing-Mei
authors.initials: QM
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D015999:Multivariate Analysis; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D016016:Proportional Hazards Models; D034622:RNA Interference; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1
chemical_list: D020413:3' Untranslated Regions; D020662:Guanine Nucleotide Exchange Factors; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human