miR‐224 promotion of cell migration and invasion by targeting Homeobox D 10 gene in human hepatocellular carcinoma

作者: Qiong Li , Chenchen Ding , Chuan Chen , Zhimin Zhang , He Xiao

DOI: 10.1111/JGH.12429

关键词:

摘要: Background and Aim MicroRNAs (miRNAs) are small noncoding RNA molecules that control target gene expression implicated in the regulation of diverse cellular pathways. In our previous research, we have demonstrated miR-224 was overexpressed liver cancer cells tissues, which an important factor cell migration invasion. This study aimed to further explore regulatory mechanism invasion cells. Methods A luciferase reporter assay used confirm HOXD10 a direct miR-224. Quantitative reverse transcriptase-polymerase chain reaction, Western blotting, Transwell migration, Matrigel assays were performed clarify molecular human hepatocellular carcinoma (HCC). Results  (i) The strongly upregulated MHHC97H MHCC97L cells, its level significantly associated with invasive potential. (ii) confirmed be Compared normal tissues had lower HCC inversely regulated (iii) promoted tumor invasion-associated proteins p-PAK4 MMP-9 by directly targeting HOXD10. Conclusion Our findings suggest previously undescribed pathway miR-224/HOXD10/p-PAK4/MMP-9 signaling contributes provides new biotarget for treatment.

参考文章(40)
Yan Li, Zhao-You Tang, Sheng-Long Ye, Yin-Kun Liu, Jie Chen, Qiong Xue, Jun Chen, Dong-Mei Gao, Wei-Hua Bao, Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97 World Journal of Gastroenterology. ,vol. 7, pp. 630- 636 ,(2001) , 10.3748/WJG.V7.I5.630
Liangjing Wang, Shujie Chen, Meng Xue, Jing Zhong, Xian Wang, Lihong Gan, Emily KY Lam, Xin Liu, Jianbin Zhang, Tianhua Zhou, Jun Yu, Hongchuan Jin, Jianmin Si, None, Homeobox D10 gene, a candidate tumor suppressor, is downregulated through promoter hypermethylation and associated with gastric carcinogenesis. Molecular Medicine. ,vol. 18, pp. 389- 400 ,(2012) , 10.2119/MOLMED.2011.00172
Yizhou Zhang, Shoichi Takahashi, Akiko Tasaka, Tadahiko Yoshima, Hidenori Ochi, Kazuaki Chayama, Involvement of microRNA-224 in cell proliferation, migration, invasion, and anti-apoptosis in hepatocellular carcinoma. Journal of Gastroenterology and Hepatology. ,vol. 28, pp. 565- 575 ,(2013) , 10.1111/J.1440-1746.2012.07271.X
Edwin A. Clark, Todd R. Golub, Eric S. Lander, Richard O. Hynes, Genomic analysis of metastasis reveals an essential role for RhoC Nature. ,vol. 406, pp. 532- 535 ,(2000) , 10.1038/35020106
Grace Wing-Yan Mak, Mandy Man-Lok Chan, Veronica Yee-Law Leong, Joyce Man-Fong Lee, Tai-On Yau, Irene Oi-Lin Ng, Yick-Pang Ching, Overexpression of a Novel Activator of PAK4, the CDK5 Kinase–Associated Protein CDK5RAP3, Promotes Hepatocellular Carcinoma Metastasis Cancer Research. ,vol. 71, pp. 2949- 2958 ,(2011) , 10.1158/0008-5472.CAN-10-4046
Soeren Torge Mees, Wolf Arif Mardin, Sonja Sielker, Edith Willscher, Norbert Senninger, Christina Schleicher, Mario Colombo-Benkmann, Joerg Haier, Involvement of CD40 Targeting miR-224 and miR-486 on the Progression of Pancreatic Ductal Adenocarcinomas Annals of Surgical Oncology. ,vol. 16, pp. 2339- 2350 ,(2009) , 10.1245/S10434-009-0531-4
Lihua Sun, Wei Yan, Yingyi Wang, Guan Sun, Hui Luo, Junxia Zhang, Xiefeng Wang, Yongping You, Zhengxiang Yang, Ning Liu, MicroRNA-10b induces glioma cell invasion by modulating MMP-14 and uPAR expression via HOXD10 Brain Research. ,vol. 1389, pp. 9- 18 ,(2011) , 10.1016/J.BRAINRES.2011.03.013
Marina N. Nikiforova, George C. Tseng, David Steward, Donna Diorio, Yuri E. Nikiforov, MicroRNA Expression Profiling of Thyroid Tumors: Biological Significance and Diagnostic Utility The Journal of Clinical Endocrinology and Metabolism. ,vol. 93, pp. 1600- 1608 ,(2008) , 10.1210/JC.2007-2696
Qiong Li, Ge Wang, Jin-Lu Shan, Zhi-Xiang Yang, Hong-Zhong Wang, Jin Feng, Ji-Jun Zhen, Chuan Chen, Zhi-Min Zhang, Wen Xu, Xi-Zhong Luo, Dong Wang, MicroRNA-224 is upregulated in HepG2 cells and involved in cellular migration and invasion. Journal of Gastroenterology and Hepatology. ,vol. 25, pp. 164- 171 ,(2010) , 10.1111/J.1440-1746.2009.05971.X
Xiaofei Zheng, Na Li, Hanjiang Fu, Yi Tie, Zheng Hu, Wei Kong, Yongge Wu, miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells Cancer Letters. ,vol. 275, pp. 44- 53 ,(2009) , 10.1016/J.CANLET.2008.09.035