| Experiment ID | EXP00279 |
| Reference | Title: TGFβR2 is a major target of miR-93 in nasopharyngeal carcinoma aggressiveness. Author: Lyu X, Fang W, Cai L, Zheng H, Ye Y, Zhang L, Li J, Peng H, Cho WC, Wang E,Marincola FM, Yao K, Cai H, Li J, Li X. Journal: Mol Cancer. 2014 Mar 8;13:51. doi: 10.1186/1476-4598-13-51. Abstract: BACKGROUND: MiR-17-92 cluster and its paralogues have emerged as crucialregulators of many oncogenes and tumor suppressors. Transforming growth factor-β receptor II (TGFβR2), as an important tumor suppressor, is involved in variouscancer types. However, it is in cancer that only two miRNAs of this cluster andits paralogues have been reported so far to regulate TGFβR2. MiR-93 is oncogenic,but its targetome in cancer has not been fully defined. The role of miR-93 innasopharyngeal carcinoma (NPC) still remains largely unknown.METHODS: We firstly evaluated the clinical signature of TGFβR2 down-regulation inclinical samples, and next used a miRNA expression profiling analysis followed bymulti-validations, including Luciferase reporter assay, to identify miRNAstargeting TGFβR2 in NPC. In vitro and in vivo studies were performed to furtherinvestigate the effects of miRNA-mediated TGFβR2 down-regulation on NPCaggressiveness. Finally, mechanism studies were conducted to explore theassociated pathway and genes influenced by this miRNA-mediated TGFβR2down-regulation.RESULTS: TGFβR2 was down-regulated in more than 50% of NPC patients. It is anunfavorable prognosis factor contributing to clinical NPC aggressiveness. Acluster set of 4 TGFβR2-associated miRNAs was identified; they are all frommiR-17-92 cluster and its paralogues, of which miR-93 was one of the mostsignificant miRNAs, directly targeting TGFβR2, promoting cell proliferation,invasion and metastasis in vitro and in vivo. Moreover, miR-93 resulted in theattenuation of Smad-dependent TGF-β signaling and the activation of PI3K/Aktpathway by suppressing TGFβR2, further promoting NPC cell uncontrolled growth,invasion, metastasis and EMT-like process. Impressively, the knockdown of TGFβR2 by siRNA displayed a consentaneous phenocopy with the effect of miR-93 in NPCcells, supporting TGFβR2 is a major target of miR-93. Our findings were alsosubstantiated by investigation of the clinical signatures of miR-93 and TGFβR2 inNPC.CONCLUSION: The present study reports an involvement of miR-93-mediated TGFβR2down-regulation in NPC aggressiveness, thus giving extended insights intomolecular mechanisms underlying cancer aggressiveness. Approaches aimed atblocking miR-93 may serve as a promising therapeutic strategy for treating NPCpatients. PMID: 24606633 |
| Expressiion Profile | Description: microRNA expression profiling of human nasopharyngeal Carcinoma tissues and Chronic Nasopharyngitis specimens Organism: Homo sapiens GEO ID: GSE43039 Platform: GPL16414 Number of samples: 40 |
| Design and Sample | Cancer Type: nasopharyngeal cancer Cancer SubType: N/D Cell Line: N/D Experimental Design: cancer vs normal Case Sample: nasopharyngeal carcinoma Control Sample: normal tissue Num of Case: 20 Num of Control: 20 Quantification Software: Limma Num of miRNAs: 315 |
| Identification | Num of Up: 4 Num of Down: 20 |