MiR-455-5p Suppresses the Progression of Prostate Cancer by Targeting CCR5

Xing, Qianwei; Xie, Huyang; Zhu, Bingye; Sun, Zhiwei; Huang, Yeqing

doi:10.1155/2019/6394784

Cited by 29 publications

(26 citation statements)

References 19 publications

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“…Reduced tumor xenograft growth [82] Maraviroc Reduced metastasis and improved overall survival (in presence of chloroquine) [144] miR-455-5p Inducted apoptosis, suppressed cellular proliferation, and tumor xenograft growth [145] Cancer-associated fibroblast, CAF; C-C chemokine ligand 5, CCL5; C-C chemokine receptor type 5, CCR5; colorectal cancer, CRC; enhancer of zeste homolog 2, EZH2; mCCR5-Ig, fusion protein that neutralizes all three CCR5 ligands; mesenchymal stem cells, MSC; myeloid-derived suppressor cell, MDSC; platelet-derived growth factor receptor, PDGFR; programmed death ligand 1, PD-L1; peripheral blood mononuclear cell, PBMC; shRNA short hairpin RNA; small interfering RNA, siRNA; tumor-associated macrophage, TAM; regulatory T cell, Treg.…”

Section: Anibaminementioning

confidence: 99%

“…CCR5 antagonist anibamine inhibited prostate cancer cell line growth with and without CCL5 stimulation in vitro, and decreased prostate cancer xenograft growth [81]. CCR5 is a target of miR-455-5p [145]. The down-regulation of CCR5 by miR-455-5p overexpression inhibited prostate cancer cell growth and induced apoptosis [145].…”

Section: Prostate Cancermentioning

confidence: 99%

“…CCR5 is a target of miR-455-5p [145]. The down-regulation of CCR5 by miR-455-5p overexpression inhibited prostate cancer cell growth and induced apoptosis [145]. In human prostate cancer tissues, miR-455-5p levels are significantly lower than in healthy tissues, suggesting miR-455-5p as a possible prognostic and diagnostic biomarker [145].…”

Section: Prostate Cancermentioning

confidence: 99%

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The CCL5/CCR5 Axis in Cancer Progression

Aldinucci

Borghese

Casagrande

2020

Cancers

285

191

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Tumor cells can “hijack” chemokine networks to support tumor progression. In this context, the C-C chemokine ligand 5/C-C chemokine receptor type 5 (CCL5/CCR5) axis is gaining increasing attention, since abnormal expression and activity of CCL5 and its receptor CCR5 have been found in hematological malignancies and solid tumors. Numerous preclinical in vitro and in vivo studies have shown a key role of the CCL5/CCR5 axis in cancer, and thus provided the rationale for clinical trials using the repurposed drug maraviroc, a CCR5 antagonist used to treat HIV/AIDS. This review summarizes current knowledge on the role of the CCL5/CCR5 axis in cancer. First, it describes the involvement of the CCL5/CCR5 axis in cancer progression, including autocrine and paracrine tumor growth, ECM (extracellular matrix) remodeling and migration, cancer stem cell expansion, DNA damage repair, metabolic reprogramming, and angiogenesis. Then, it focuses on individual hematological and solid tumors in which CCL5 and CCR5 have been studied preclinically. Finally, it discusses clinical trials of strategies to counteract the CCL5/CCR5 axis in different cancers using maraviroc or therapeutic monoclonal antibodies.

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Section: Anibaminementioning

confidence: 99%

Section: Prostate Cancermentioning

confidence: 99%

Section: Prostate Cancermentioning

confidence: 99%

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The CCL5/CCR5 Axis in Cancer Progression

Aldinucci

Borghese

Casagrande

2020

Cancers

285

191

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“…In case of prostate cancer, the miR-455-5p tumor suppressor function has been shown to significantly suppress proliferation and initiate apoptosis of prostate cancer cells. The authors also experimentally determined a functional target for miR-455-5p -CCR5 gene [82].…”

Section: Downregulated Micrornas Associated With Lymphatic Disseminatmentioning

confidence: 99%

miRNAs expression signature potentially associated with lymphatic dissemination in locally advanced prostate cancer

et al. 2020

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Background Prostate cancer is one of the most common and socially significant cancers among men. The aim of our study was to reveal changes in miRNA expression profiles associated with lymphatic dissemination in prostate cancer and to identify the most prominent miRNAs as potential prognostic markers for future studies. Methods High-throughput miRNA sequencing was performed for 44 prostate cancer specimens taken from Russian patients, with and without lymphatic dissemination (N1 – 20 samples; N0 – 24 samples). Results We found at least 18 microRNAs with differential expression between N0 and N1 sample groups: miR-182-5p, miR-183-5p, miR-96-5p, miR-25-3p, miR-93-5p, miR-7-5p, miR-615-3p, miR-10b, miR-1248 (N1-miRs; elevated expression in N1 cohort; p < 0.05); miR-1271-5p, miR-184, miR-222-3p, miR-221-5p, miR-221-3p, miR-455-3p, miR-143-5p, miR-181c-3p and miR-455-5p (N0-miRs; elevated expression in N0; p < 0.05). The expression levels of N1-miRs were highly correlated between each other (the same is applied for N0-miRs) and the expression levels of N0-miRs and N1-miRs were anti-correlated. The tumor samples can be divided into two groups depending on the expression ratio between N0-miRs and N1-miRs. Conclusions We found the miRNA expression signature associated with lymphatic dissemination, in particular on the Russian patient cohort. Many of these miRNAs are well-known players in either oncogenic transformation or tumor suppression. Further experimental studies with extended sampling are required to validate these results.

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“…A high plasma level of CCL3 was associated with poor survival rate in chronic lymphocytic leukemia [ 66 ] and diffuse-large B-cell lymphoma [ 67 ]. CCR5 was reported to be associated with poor overall survival in breast cancer [ 34 ], poor relapse-free survival in prostate cancer [ 68 ], high histological grade in pancreatic cancer [ 35 ], and perineural invasion in salivary adenoid cystic carcinoma [ 36 ]. The present study is the first report which revealed that the expression of both CCL3 and CCR5 in human cancer tissue is associated with poor patient prognosis.…”

Section: Discussionmentioning

confidence: 99%

CCL3–CCR5 axis contributes to progression of esophageal squamous cell carcinoma by promoting cell migration and invasion via Akt and ERK pathways

Kodama

Koma

Arai

et al. 2020

Laboratory Investigation

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Tumor-associated macrophages (TAMs) contribute to the progression and mortality of various malignancies. We reported that high numbers of infiltrating TAMs were significantly associated with tumor progression and poor prognosis in esophageal squamous cell carcinoma (ESCC). In our previous investigation of TAMs’ actions in ESCC, we compared gene expression profiles between peripheral blood monocyte (PBMo)-derived macrophages and TAM-like macrophages stimulated with conditioned media of ESCC cell lines. Among the upregulated genes in the TAM-like macrophages, we focused on CC chemokine ligand 3 ( CCL3 ), which was reported to contribute to tumor progression in several malignancies. Herein, we observed that not only TAMs but also ESCC cell lines expressed CCL3. A CCL3 receptor, CC chemokine receptor 5 (CCR5) was expressed in the ESCC cell lines. Treating the ESCC cell lines with recombinant human (rh)CCL3 induced the phosphorylations of Akt and ERK, which were suppressed by CCR5 knockdown. Migration and invasion of ESCC cells were promoted by treatment with rhCCL3 and co-culture with TAMs. TAMs/rhCCL3-promoted cell migration and invasion were suppressed by inhibition of the CCL3–CCR5 axis, PI3K/Akt, and MEK/ERK pathways. Treatment with rhCCL3 upregulated MMP2 and VEGFA expressions in ESCC cell lines. Our immunohistochemical analysis of 68 resected ESCC cases showed that high expression of CCL3 and/or CCR5 in ESCC tissues was associated with poor prognosis. High CCR5 expression was associated with deeper invasion, presence of vascular invasion, higher pathological stage, higher numbers of infiltrating CD204 + TAMs, and higher microvascular density. High expression of both CCL3 and CCR5 was an independent prognostic factor for disease-free survival. These results suggest that CCL3 derived from both TAMs and cancer cells contributes to the progression and poor prognosis of ESCC by promoting cell migration and invasion via the binding of CCR5 and the phosphorylations of Akt and ERK. The CCL3–CCR5 axis could become the target of new therapies against ESCC.

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MiR-455-5p Suppresses the Progression of Prostate Cancer by Targeting CCR5

Cited by 29 publications

References 19 publications

The CCL5/CCR5 Axis in Cancer Progression

The CCL5/CCR5 Axis in Cancer Progression

miRNAs expression signature potentially associated with lymphatic dissemination in locally advanced prostate cancer

CCL3–CCR5 axis contributes to progression of esophageal squamous cell carcinoma by promoting cell migration and invasion via Akt and ERK pathways

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