Dysregulated microRNA-224/apelin axis associated with aggressive progression and poor prognosis in patients with prostate cancer

Wan, Yuqing; Zeng, Zhao Chong; Xi, Mian; Song, Wan; Hua, Wei; Liu, Yuanling; Zhou, Yanmin; Luo, Hongwei; Jiang, Funeng; Zhong, Weide

doi:10.1016/j.humpath.2014.10.027

Cited by 64 publications

(55 citation statements)

References 35 publications

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“…Studies in chronic liver diseases have also shown that hypoxia and inflammatory conditions are capable of inducing apelin expression, which creates an angiogenic and fibroproliferative response [40]. Additionally, Wan et al demonstrated that apelin is a target gene for microRNA-224 (miR-224) and that low miR-224 levels correlates with elevated apelin levels in prostate cancer tissues, which is associated with increased cancer progression, advanced stage, and decreased disease-free survival [41]. …”

Section: Discussionmentioning

confidence: 99%

Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth

et al. 2017

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Purpose Cholangiocarcinoma (CCA) is a malignancy of the biliary epithelium that is associated with low five-year survival. The apelin receptor (APLNR), which is activated by the apelin peptide, has not been studied in CCA. The purpose of this study is to determine if inhibition of the apelin/APLNR axis can inhibit CCA growth. Methods Immunohistochemistry, rtPCR, immunofluorescence, flow cytometry, and ELISA was used to measure APLNR expression in human CCA cells and tissues. Mz-ChA-1 cells were treated with increasing concentrations of apelin and ML221, an APLNR antagonist. Expression of proliferative and angiogenic genes were measured via rtPCR. In vivo, Mz-ChA-1 cells were injected into the flanks of nu/nu mice, which were treated with ML221 (150 μg/kg) via tail vein injection. Results Expression of the apelin/APLNR axis was increased in CCA. In vitro, CCA proliferation and angiogenesis was inhibited by ML221 treatment. ML221 treatment significantly decreased tumor growth in nu/nu mice. Conclusion The apelin/APLNR axis regulates CCA proliferation and angiogenesis. Inhibition of the apelin/APLNR axis decreases tumor growth in our xenograft model. Targeting APLNR signaling has the potential to serve as a novel, tumor directed therapy for CCA.

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Section: Discussionmentioning

confidence: 99%

Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth

et al. 2017

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“…In glioblastoma, miR-224 overexpression increases radiation sensitivity, thus improving outcomes, and patients with high miR-224 expression levels reportedly have a better overall survival [20]. Finally, miR22-4 downregulation was found to promote tumor progression in prostate cancer [33]. It is also worth mentioning the recent finding that, although miR-224 upregulation is a known negative prognostic factor in HCC, the high miR-224 phenotype in this cancer has been found associated with a better response to sorafenib, an inhibitor of several tyrosine kinase receptors, such as RET, RAF kinase, and vascular endothelial growth factor (VEGF) receptor, that is also used in MTC [34].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of miR-224 and RAS Mutations in Medullary Thyroid Carcinoma

Cavedon

Barollo

Bertazza

et al. 2017

International Journal of Endocrinology

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Little is known about the function of microRNA-224 (miR-224) in medullary thyroid cancer (MTC). This study investigated the role of miR-224 expression in MTC and correlated it with mutation status in sporadic MTCs. A consecutive series of 134 MTCs were considered. Patients had a sporadic form in 80% of cases (107/134). In this group, REarranged during transfection (RET) and rat sarcoma (RAS) mutation status were assessed by direct sequencing in the tumor tissues. Quantitative real-time polymerase chain reaction was used to quantify mature hsa-miR-224 in tumor tissue. RAS (10/107 cases, 9%) and RET (39/107 cases, 36%) mutations were mutually exclusive in sporadic cases. miR-224 expression was significantly downregulated in patients with the following: high calcitonin levels at diagnosis (p = 0.03, r = −0.3); advanced stage (p = 0.001); persistent disease (p = 0.001); progressive disease (p = 0.002); and disease-related death (p = 0.0001). We found a significant positive correlation between miR-224 expression and somatic RAS mutations (p = 0.007). Patients whose MTCs had a low miR-224 expression tended to have a shorter overall survival (log-rank test p = 0.005). On multivariate analysis, miR-224 represented an independent prognostic marker. Our data indicate that miR-224 is upregulated in RAS-mutated MTCs and in patients with a better prognosis and could represent an independent prognostic marker in MTC patients.

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“…Previous studies have shown that miR-224 can bind to the tumor suppressors of TNFα-induced protein 1 (TNFAIP1) and Smad4, Raf kinase inhibitor protein (RKIP), apoptosis inhibitor-5 (API-5), PH domain leucine-rich-repeat protein phosphatase 1 (PHLPP1), and PHLPP2 to promote the survival and proliferation of colorectal cancer (CRC) and hepatocellular carcinoma (HCC), but bind to the TRIB1 to promote apoptosis of prostatic cancer cells [7–11]. Furthermore, miR224 binds to the Smad4 and Homeobox D10 (HOXD10) to promote migration of HCC and CRC [8, 12] while it binds to the TPD52 to inhibit migration of prostatic cancer PCa cells [13].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-224 inhibits proliferation and migration of breast cancer cells by down-regulating Frizzled 5 expression

Liu

Shen

et al. 2016

Oncotarget

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The Wnt/β-catenin signaling is crucial for the proliferation and migration of breast cancer cells. However, the expression of microRNA-224 (miR-224) in the different types of breast cancers and its role in the Wnt/β-catenin signaling and the proliferation and migration of breast cancer cells are poorly understood. In this study, the levels of miR-224 in different types of breast cancer tissues and cell lines were examined by quantitative RT-PCR and the potential targets of miR-224 in the Wnt/β-catenin signaling were investigated. The effects of altered miR-224 expression on the frequency of CD44+CD24− cancer stem-like cells (CSC), proliferation and migration of MCF-7 and MDA-MB-231 cells were examined by flow cytometry, MTT and transwell migration. We found that the levels of miR-224 expression in different types of breast cancer tissues and cell lines were associated inversely with aggressiveness of breast cancers. Enhanced miR-224 expression significantly reduced the fizzled 5-regulated luciferase activity in 293T cells, fizzled 5 expression in MCF-7 and MDA-MB-231 cells, the β-dependent luciferase activity in MCF-7 cells, and the nuclear translocation of β-catenin in MDA-MB-231 cells. miR-224 inhibition significantly increased the percentages of CSC in MCF-7 cells and enhanced proliferation and migration of MCF-7 cells. Enhanced miR-224 expression inhibited proliferation and migration of MDA-MB-231 cells, and the growth of implanted breast cancers in vivo. Induction of frizzled 5 over-expression mitigated the miR-224-mediated inhibition of breast cancer cell proliferation. Collectively, these data indicated that miR-224 down-regulated the Wnt/β-catenin signaling possibly by binding to frizzled 5 and inhibited proliferation and migration of breast cancer cells.

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Dysregulated microRNA-224/apelin axis associated with aggressive progression and poor prognosis in patients with prostate cancer

Cited by 64 publications

References 35 publications

Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth

Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth

Prognostic Impact of miR-224 and RAS Mutations in Medullary Thyroid Carcinoma

MicroRNA-224 inhibits proliferation and migration of breast cancer cells by down-regulating Frizzled 5 expression

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