MiR-199a-5p suppresses human bladder cancer cell metastasis by targeting CCR7.

Mi Zhou,Feng Liu,Dahong Zhang,Qi Zhang,Shuai Wang,Linyi Hu

doi:10.1186/s12894-016-0181-3

Mi Zhou, Feng Liu + Show 4 more

Open Access

https://doi.org/10.1186/s12894-016-0181-3

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Journal: BMC Urology	Publication Date: Nov 4, 2016
Citations: 40	License type: cc-by

Affiliation: Zhejiang Provincial People's Hospital

Abstract

BackgroundC-C chemokine receptor type 7 (CCR7) overexpression correlated with lymphatic metastasis and poor prognosis is a major obstacle to bladder cancer treatment. Recent studies have revealed that miR-199a-5p was significantly abnormal expressed in several solid tumors and functioned as oncogene or tumor suppressor. This study was aimed to further investigate the effects of miR-199a-5p on the cell metastasis mediated by CCR7 in bladder cancer.MethodsQuantitative Real Time PCR (qRT-PCR) was firstly performed to identified the expression of miR-199a-5p and CCR7 in human bladder cancer samples and cell lines. Following that, the effects of miR-199a-5p on cell migratory and invasive activities were assessed by wound healing and Matrigel invasion assays, respectively. Finally, luciferase reporter assay and western blot were employed to investigate whether CCR7 could directly interact with miR-199a-5p.ResultsmiR-199a-5p downregulation and CCR7 upregulation were firstly observed in bladder cancer samples and cell lines. In addition, both miR-199a-5p downregulation and CCR7 upregulation were significantly involved in bladder cancer clinicopathological features. Moreover, overexpression of miR-199a-5p could inhibit baldder cancer cell migration and invasion. miR-199a-5p was confirmed to be able to target the 3′ untranslated region (UTR) of CCR7 and regulate the expression of CCR7, Matrix metalloproteinases 9 (MMP-9) and Epithelial-Mesenchymal Transition (EMT)-related proteins.ConclusionOur findings added newer insights into the multifaceted role played by miR-199a-5p/CCR7 in bladder cancer, prompting for the first time this miRNA/chemokine axis that regulates cell metastasis. The results strongly supported miR-199a-5p as a potential therapeutic agent and diagnostic marker of bladder cancer.

Highlights

C-C chemokine receptor type 7 (CCR7) overexpression correlated with lymphatic metastasis and poor prognosis is a major obstacle to bladder cancer treatment
Results miR-199a-5p expression was downregulated and CCR7 expression was upregulated in human bladder cancer tissue samples and cell lines To determine whether miR-199a-5p was involved in the tumourigenesis of human bladder cancer, we evaluated the expression levels of miR-199a-5p in human bladder cancer tissue samples and cell lines by Quantitative Real Time PCR (qRT-PCR)
Correlation of miR-199a-5p and CCR7 expression with clinicopathological factors As shown in Table 1, miR-199a-5p downregulation was correlated with TNM stage (P < 0.001), Histological grade (P = 0.003), Tumor invasion depth (T) (P < 0.001) and Lymph node metastasis (N) (P < 0.001)

Summary

Introduction

C-C chemokine receptor type 7 (CCR7) overexpression correlated with lymphatic metastasis and poor prognosis is a major obstacle to bladder cancer treatment. This study was aimed to further investigate the effects of miR-199a-5p on the cell metastasis mediated by CCR7 in bladder cancer. 25 % of bladder cancer cases are muscle invasive which is more aggressive and with a much worse prognosis [1, 2]. While the recurrence and mortality is still high to those with muscleinvasive bladder cancer. Patients with recurrent or metastatic bladder cancer just remains 14–15 months. Previous studies have demonstrated CCR7 overexpression correlates with lymphatic metastasis and poor prognosis in breast cancer, colon cancer, prostate cancer and gastric cancer [9,10,11,12]. We have found that CCR7 and its ligand CCL21 promote T24 cell proliferation and enhance its migration and invasion via upregulation MMP-2 and MMP-9 [13]

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