有哪些信誉好的足球投注网站an artificial mirna against hpse suppresses melanoma invasion properties, correlating with a down-regulation of chemokines and mapk phosphorylation人造microrna与hpse抑制黑素瘤入侵属性,关联的下调趋化因子和mapk磷酸化.pdfVIP
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an artificial mirna against hpse suppresses melanoma invasion properties, correlating with a down-regulation of chemokines and mapk phosphorylation人造microrna与hpse抑制黑素瘤入侵属性,关联的下调趋化因子和mapk磷酸化
An Artificial miRNA against HPSE Suppresses Melanoma
Invasion Properties, Correlating with a Down-Regulation
of Chemokines and MAPK Phosphorylation
Xiaoyan Liu, Hong Fang*, Hongchao Chen, Xiaoling Jiang, Deren Fang, Yan Wang, Dingxian Zhu
Department of Dermatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China
Abstract
Ribonucleic acid interference (RNAi) based on microRNA (miRNA) context may provide an efficient and safe therapeutic
knockdown effect and can be driven by ribonucleic acid polymerase II (RNAP II). In this study, we designed and synthesized
miR155-based artificial miRNAs against heparanase (HPSE) constructed with BLOCK-iTTM Pol II miR RNAi Expression Vector
Kit. The expression levels of HPSE declined significantly in both the mRNA and protein levels in HPSE-miRNA transfected
melanoma cells that exhibited reduction of adhesion, migration, and invasion ability in vitro and in vivo. We also observed
that HPSE miRNA could inhibit the expressions of chemokines of interleukin-8 (IL8) and chemokine (C-X-C motif) ligand 1
(CXCL1), at both the transcriptional and translational levels. Further study on its probable mechanism declared that down-
regulation of IL8 and CXCL1 by HPSE-miRNA may be correlated with reduced growth-factor simulated mitogen-activated
kinase (MAPK) phosphorylation including p38 MAPK, c-Jun N-terminal kinase (JNK) and extracellular-signal-regulated kinase
(ERK) 1 and 2, which could be rescued by miRNA incompatible mutated HPSE cDNA. In conclusion, we demonstrated that
artificial miRNAs against HPSE might serve as an alterative mean of therapy to low HPSE expression and to block the
adhesion, invasion, and metastasis of melanoma cells. Furthermore, miRNA-based RNAi was also a powerful tool for gene
function study.
Citation: Liu X
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