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MiRNALet‐7a mediates prostate cancer PC‐3 cell invasion, migration by inducing epithelial‐mesenchymal transition through CCR7/MAPK pathway
Author(s) -
Tang Guanlin,
Du Ruoyang,
Tang Zhaobing,
Kuang Youlin
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26595
Subject(s) - prostate cancer , c c chemokine receptor type 7 , cancer research , microrna , epithelial–mesenchymal transition , transfection , metastasis , mapk/erk pathway , biology , cancer cell , cancer , microbiology and biotechnology , chemistry , cell culture , chemokine receptor , signal transduction , chemokine , immunology , gene , genetics , inflammation
Prostate cancer is one of the most common malignancies in older men. Recent evidence has demonstrated microRNA (miRNA) Let‐7a expression decreased in prostate cancer, while the expression of CC chemokine receptor type 7 (CCR7) increased. In this study, we investigated whether CCR7 overexpression was associated with a decrease in the expression of miRNA Let‐7a in invasion and metastasis of prostate cancer cell. Synthetic Let‐7a mimics and Let‐7a inhibitors were transfected into prostate cancer PC‐3 cells, respectively. Then Western blot was used to detect the expression of CCR7, ERK, p38, MMP‐9, and Epithelial‐Mesenchymal Transition (EMT)‐related proteins. Matrigel invasion assays were performed to assess the migratory and invasive activities of PC3 cells. To confirm the fact that 3′UTR of CCR7 is a direct target of Let‐7a, a luciferase assay for the reporter gene expressing the Let‐7a binding sites of CCR7 3′UTR was used. Synthetic Let‐7a mimics decreased prostate cancer cell migration and invasion, as well as the expression of CCR7, phospho‐p38, phospho‐ERK1/2, MMP‐9, N‐cadherin, and Snail in PC‐3 cells. The Let‐7a inhibitors reversed the effects of Let‐7a on PC‐3 cells. The 3′UTR of CCR7 was confirmed as a direct target of Let‐7a by using the luciferase assay. All findings demonstrated that Let‐7a/CCR7 axis regulated EMT progress in prostate cancer cells and mediated the tumor cell invasion and migration process via activation of P38/ERK signal pathway. Our results suggested that the therapeutic potential of Let‐7a as an antitumor and antimetastatic manager in prostate cancer and CCR7 may be regarded as a therapeutic target for the prostate cancer treatment.