MicroRNA‐224 inhibits progression of human prostate cancer by downregulating TRIB1

• Published in: International journal of cancer 2014-08, Vol.135 (3), p.541-550
• Main Authors: Lin, Zhuo‐Yuan, Huang, Ya‐Qiang, Zhang, Yan‐Qiong, Han, Zhao‐Dong, He, Hui‐Chan, Ling, Xiao‐Hui, Fu, Xin, Dai, Qi‐Shan, Cai, Chao, Chen, Jia‐Hong, Liang, Yu‐Xiang, Jiang, Fu‐Neng, Zhong, Wei‐De, Wang, Fen, Wu, Chin‐Lee
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Apoptosis; biochemical recurrence‐free survival; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Blotting, Western; Cancer; Cell Movement; Cell Proliferation; clinicopathological feature; Disease Progression; Flow Cytometry; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; In Situ Hybridization; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Male; Medical prognosis; Medical research; Metastasis; MicroRNAs; MicroRNAs - genetics; microRNA‐224; Middle Aged; Neoplasm Grading; Neoplasm Staging; Prognosis; Prostate - metabolism; Prostate - pathology; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Survival Rate; Tissue Array Analysis; TRIB1; Tumor Cells, Cultured
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.28707

Our previous microarray data showed that microRNA‐224 (miR‐224) was downregulated in human prostate cancer (PCa) tissues compared with adjacent benign tissues. However, the underlying mechanisms by which miR‐224 is involved in PCa remain unclear. In this study, we identified TRIB1 as a target gene of miR‐224. Forced expression of miR‐224 suppressed PCa cell proliferation, invasion and migration, and promoted cell apoptosis by downregulating TRIB1. Moreover, the expression level of miR‐224 in PCa tissues was negatively correlated with that of TRIB1. miR‐224 downregulation was frequently found in PCa tissues with metastasis, higher PSA level and clinical stage, whereas TRIB1 upregulation was significantly associated with metastasis. Both miR‐224 downregulation and TRIB1 upregulation were significantly associated with poor biochemical recurrence‐free survival of patients with PCa. In conclusion, these findings reveal that the aberrant expression of miR‐224 and TRIB1 may promote PCa progression and have potentials to serve as novel biomarkers for PCa prognosis. What's new? Dysregulation of microRNA expression in cancer suggests that small, noncoding RNAs could be valuable biomarkers for disease detection and management. This study examined the role of miR‐224 expression in prostate cancer. The findings indicate that abnormal miR‐224 expression and its target TRIB1, a regulator of intracellular signalling, may be associated with aggressive progression and poor prognosis of prostate cancer. The tumor suppressive effects of miR‐224 in prostate cancer may be partially mediated by down‐regulating TRIB1 expression.