Tags

Type your tag names separated by a space and hit enter

MicroRNA-451: epithelial-mesenchymal transition inhibitor and prognostic biomarker of hepatocelluar carcinoma.
Oncotarget. 2015 Jul 30; 6(21):18613-30.O

Abstract

Increasing evidence indicates that dysregulation of microRNAs (miRNAs) plays critical roles in malignant transformation and tumor progression. Previously, we have shown that microRNA-451 (miR-451) inhibits growth, increases chemo- or radiosensitivity and reverses epithelial to mesenchymal transition (EMT) in lung cancer. However, the roles of miR-451 in hepatocelluar carcinoma (HCC) progression and metastasis are still largely unknown. Reduced miR-451 in HCC tissues was observed to be significantly correlated with advanced clinical stage, metastasis and worse disease-free or overall survival. Through gain- and loss-of function experiments, we demonstrated that miR-451 inhibited cell growth, induced G0/G1 arrest and promoted apoptosis in HCC cells. Importantly, miR-451 could inhibit the migration and invasion in vitro, as well as in vivo metastasis of HCC cells through regulating EMT process. Moreover, the oncogene c-Myc was identified as a direct and functional target of miR-451 in HCC cells. Knockdown of c-Myc phenocopied the effects of miR-451 on EMT and metastasis of HCC cells, whereas overexpression of c-Myc partially attenuated the functions of miR-451 restoration. Furthermore, miR-451 downregulation-induced c-Myc overexpression leads to the activation of Erk1/2 signaling, which induces acquisition of EMT phenotype through regulation of GSK-3β/snail/E-cadherin and the increased expression of MMPs family members in HCC cells. Collectively, these data demonstrated that miR-451 is a novel prognostic biomarker for HCC patients and that function as a potential metastasis inhibitor in HCC cells through activation of the Erk1/2 signaling, at least partially by targeting c-Myc. Thus, targeting miR-451/c-Myc/Erk1/2 axis may be a potential strategy for the treatment of metastatic HCC.

Authors+Show Affiliations

Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.Department of Hepatobiliary Surgery, First Hospital Affiliated to The Chinese PLA General Hospital, Beijing, China.Liver Disease Center of PLA, The 81th Hospital of PLA, Nanjing, Jiangsu, China.Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26164082

Citation

Huang, Jia-Yuan, et al. "MicroRNA-451: Epithelial-mesenchymal Transition Inhibitor and Prognostic Biomarker of Hepatocelluar Carcinoma." Oncotarget, vol. 6, no. 21, 2015, pp. 18613-30.
Huang JY, Zhang K, Chen DQ, et al. MicroRNA-451: epithelial-mesenchymal transition inhibitor and prognostic biomarker of hepatocelluar carcinoma. Oncotarget. 2015;6(21):18613-30.
Huang, J. Y., Zhang, K., Chen, D. Q., Chen, J., Feng, B., Song, H., Chen, Y., Zhu, Z., Lu, L., De, W., Wang, R., & Chen, L. B. (2015). MicroRNA-451: epithelial-mesenchymal transition inhibitor and prognostic biomarker of hepatocelluar carcinoma. Oncotarget, 6(21), 18613-30.
Huang JY, et al. MicroRNA-451: Epithelial-mesenchymal Transition Inhibitor and Prognostic Biomarker of Hepatocelluar Carcinoma. Oncotarget. 2015 Jul 30;6(21):18613-30. PubMed PMID: 26164082.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-451: epithelial-mesenchymal transition inhibitor and prognostic biomarker of hepatocelluar carcinoma. AU - Huang,Jia-Yuan, AU - Zhang,Kai, AU - Chen,Dong-Qin, AU - Chen,Jing, AU - Feng,Bing, AU - Song,Haizhu, AU - Chen,Yitian, AU - Zhu,Ziman, AU - Lu,Lei, AU - De,Wei, AU - Wang,Rui, AU - Chen,Long-Bang, PY - 2014/12/12/received PY - 2015/05/12/accepted PY - 2015/7/13/entrez PY - 2015/7/15/pubmed PY - 2016/6/1/medline KW - c-Myc KW - epithelial-mesenchymal transition KW - hepatocellular carcinoma KW - invasion KW - miR-451 SP - 18613 EP - 30 JF - Oncotarget JO - Oncotarget VL - 6 IS - 21 N2 - Increasing evidence indicates that dysregulation of microRNAs (miRNAs) plays critical roles in malignant transformation and tumor progression. Previously, we have shown that microRNA-451 (miR-451) inhibits growth, increases chemo- or radiosensitivity and reverses epithelial to mesenchymal transition (EMT) in lung cancer. However, the roles of miR-451 in hepatocelluar carcinoma (HCC) progression and metastasis are still largely unknown. Reduced miR-451 in HCC tissues was observed to be significantly correlated with advanced clinical stage, metastasis and worse disease-free or overall survival. Through gain- and loss-of function experiments, we demonstrated that miR-451 inhibited cell growth, induced G0/G1 arrest and promoted apoptosis in HCC cells. Importantly, miR-451 could inhibit the migration and invasion in vitro, as well as in vivo metastasis of HCC cells through regulating EMT process. Moreover, the oncogene c-Myc was identified as a direct and functional target of miR-451 in HCC cells. Knockdown of c-Myc phenocopied the effects of miR-451 on EMT and metastasis of HCC cells, whereas overexpression of c-Myc partially attenuated the functions of miR-451 restoration. Furthermore, miR-451 downregulation-induced c-Myc overexpression leads to the activation of Erk1/2 signaling, which induces acquisition of EMT phenotype through regulation of GSK-3β/snail/E-cadherin and the increased expression of MMPs family members in HCC cells. Collectively, these data demonstrated that miR-451 is a novel prognostic biomarker for HCC patients and that function as a potential metastasis inhibitor in HCC cells through activation of the Erk1/2 signaling, at least partially by targeting c-Myc. Thus, targeting miR-451/c-Myc/Erk1/2 axis may be a potential strategy for the treatment of metastatic HCC. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/26164082/MicroRNA_451:_epithelial_mesenchymal_transition_inhibitor_and_prognostic_biomarker_of_hepatocelluar_carcinoma_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=4317 DB - PRIME DP - Unbound Medicine ER -