Tumor suppressive microRNA-200a inhibits renal cell carcinoma development by directly targeting TGFB2

Lu, Rui-Jing; Ji, Zhonghua; Li, Xiaoqing; Qin, Jie; Cui, Guanghui; Chen, Jing; Zhai, Qian; Zhao, Chenchen; Zhang, Wei; Yu, Zhen

doi:10.1007/s13277-015-3355-9

Cited by 25 publications

(21 citation statements)

References 43 publications

(56 reference statements)

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“…The results of the co-transfection experiments using constructs encoding eGFP-3′-UTR of TGFβ2 and DsRed-miR-200a revealed that miR-200a directly bound the 3′-UTR of TGFβ2 and silenced its expression. Our identification of chicken TGFβ2 as a target of gga-miR-200a-3p is consistent with earlier reports in mice and humans [38,39] and, to our knowledge, for the first time, two other genes, MAP2K4 and ZAK, were also identified as the targets of gga-miR-200a-3p in this study. ZAK is a MAPK-kinase kinase (MKKK) which was involved in the activation of the ERK, p38 signaling pathways [40,41].…”

Section: Discussionsupporting

confidence: 93%

MicroRNA gga-miR-200a-3p modulates immune response via MAPK signaling pathway in chicken afflicted with necrotic enteritis

Pham

Ban

Lee

et al. 2020

Vet Res

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MicroRNAs (miRNAs) are small non-coding RNAs that contribute to host immune response as post-transcriptional regulation. The current study investigated the biological role of the chicken (Gallus gallus) microRNA-200a-3p (gga-miR-200a-3p), using 2 necrotic enteritis (NE) afflicted genetically disparate chicken lines, 6.3 and 7.2, as well as the mechanisms underlying the fundamental signaling pathways in chicken. The expression of gga-miR-200a-3p in the intestinal mucosal layer of NE-induced chickens, was found to be upregulated during NE infection in the diseasesusceptible chicken line 7.2. To validate the target genes, we performed an overexpression analysis of gga-miR-200a-3p using chemically synthesized oligonucleotides identical to gga-miR-200a-3p, reporter gene analysis including luciferase reporter assay, and a dual fluorescence reporter assay in cultured HD11 chicken macrophage cell lines. Gga-miR-200a-3p was observed to be a direct transcriptional repressor of ZAK, MAP2K4, and TGFβ2 that are involved in mitogen-activated protein kinase (MAPK) pathway by targeting the 3′-UTR of their transcripts. Besides, gga-miR-200a-3p may indirectly affect the expression of protein kinases including p38 and ERK1/2 at both transcriptional and translational levels, suggesting that this miRNA may function as an important regulator of the MAPK signaling pathway. Proinflammatory cytokines consisting of IL-1β, IFN-γ, IL-12p40, IL-17A, and LITAF belonging to Th1 and Th17-type cytokines, were upregulated upon gga-miR-200a-3p overexpression. These findings have enhanced our knowledge of the immune function of gga-miR-200a-3p mediating the chicken immune response via regulation of the MAPK signaling pathway and indicate that this miRNA may serve as an important biomarker of diseases in domestic animals. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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Section: Discussionsupporting

confidence: 93%

MicroRNA gga-miR-200a-3p modulates immune response via MAPK signaling pathway in chicken afflicted with necrotic enteritis

Pham

Ban

Lee

et al. 2020

Vet Res

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“…Moreover, IL17, as a representative of interleukins, is associated with lung and colorectal cancer progression and predicts poor prognosis in breast cancer [8–10]. Even though some studies suggested an impact in RCC, the role of cytokines and chemokines in RCC progression is poorly understood [1, 11, 12]. From a clinical point of view, cytokine and chemokine secretion into the blood stream makes them very suitable as noninvasive clinical markers.…”

Section: Introductionmentioning

confidence: 99%

Different Cytokine and Chemokine Expression Patterns in Malignant Compared to Those in Nonmalignant Renal Cells

Gelbrich

Ahrend

Kaul

et al. 2017

Analytical Cellular Pathology

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Objective Cytokines and chemokines are widely involved in cancer cell progression and thus represent promising candidate factors for new biomarkers. Methods Four renal cell cancer (RCC) cell lines (Caki-1, 786-O, RCC4, and A498) and a nonmalignant renal cell line (RC-124) were examined with respect to their proliferation. The cytokine and chemokine expression pattern was examined by a DNA array (Human Cytokines & Chemokines RT2 Profiler PCR Array; Qiagen, Hilden, Germany), and expression profiles were compared. Results Caki-1 and 786-O cells exhibited significantly increased proliferation rates, whereas RCC4 and A498 cells demonstrated attenuated proliferation, compared to nonmalignant RC-124 cells. Expression analysis revealed 52 cytokines and chemokines primarily involved in proliferation and inflammation and differentially expressed not only in malignant and nonmalignant renal cells but also in the four RCC cell lines. Conclusion This is the first study examining the expression of 84 cytokines and chemokines in four RCC cell lines compared to that in a nonmalignant renal cell line. VEGFA, NODAL, and BMP6 correlated with RCC cell line proliferation and, thus, may represent putative clinical biomarkers for RCC progression as well as for RCC diagnosis and prognosis.

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“…In the past decades, the roles of cellular miRNA abnormalities in the pathogenesis of most human cancers have been intensely investigated. [25][26][27] Furthermore, the miR-200a-3p/ CBL pathway has not been explored in RCC. In the current study, we focused on understanding the pathological roles of miR-200a-3p in RCC.…”

Section: Discussionmentioning

confidence: 99%

“…[26][27][28] To further uncover the underlying mechanisms of the suppression of RCC cell growth and migration mediated by miR-200a-3p, we searched for miRNA targets and identified CBL as a novel target of miR-200a-3p. [26][27][28] To further uncover the underlying mechanisms of the suppression of RCC cell growth and migration mediated by miR-200a-3p, we searched for miRNA targets and identified CBL as a novel target of miR-200a-3p.…”

Section: Discussionmentioning

confidence: 99%

Decreased miR‐200a‐3p is a key regulator of renal carcinoma growth and migration by directly targeting CBL

Ding

Sun

Zhong

et al. 2018

J of Cellular Biochemistry

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Although emerging evidence has revealed that microRNAs (miRNAs) dysregulation contribute to carcinogenesis, the mechanism underlying their roles in renal cell carcinoma (RCC) is unclear. The purpose of the current study was to analyze the association of miR-200a-3p expression with RCC and to understand potential novel target genes, functions and mechanisms of miR-200a-3p in RCC. MiR-200a-3p expression levels were first measured by quantitative real-time polymerase chain reaction and in situ hybridization in pairs of RCC tissue samples. Next, the potential miR-200a-3p target gene was analyzed using a combination of computer-aided algorithms, luciferase reporter assays and Western blot analysis. Finally, the biological roles of miR-200a-3p in RCC tumorigenesis were investigated both in vitro by 5-ethynyl-20-deoxyuridine, apoptosis assay and transwell assay, as well as in vivo using a xenograft mouse model. Our results demonstrated that miR-200a-3p was remarkably downregulated in RCC tissues compared with normal adjacent tissue, and CBL is a direct target of miR-200a-3p. An inverse correlation between miR-200a-3p and CBL was observed in RCC tissue samples. Mechanistic investigations revealed that ectopic expression of miR-200a-3p in RCC cell lines suppressed cell proliferation and migration and enforced cell apoptosis by directly inhibiting CBL in vitro and in vivo, whereas silencing miR-200a-3p resulted in the opposite effects. Additionally, overexpressing CBL abolished the effects induced by miR-200a-3p overexpression. Taken together, our results show that the miR-200a-3p/CBL regulation axis is a novel mechanism underlying RCC pathogenesis and may serve as a candidate biomarker and therapeutic target in RCC.

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Tumor suppressive microRNA-200a inhibits renal cell carcinoma development by directly targeting TGFB2

Cited by 25 publications

References 43 publications

MicroRNA gga-miR-200a-3p modulates immune response via MAPK signaling pathway in chicken afflicted with necrotic enteritis

MicroRNA gga-miR-200a-3p modulates immune response via MAPK signaling pathway in chicken afflicted with necrotic enteritis

Different Cytokine and Chemokine Expression Patterns in Malignant Compared to Those in Nonmalignant Renal Cells

Decreased miR‐200a‐3p is a key regulator of renal carcinoma growth and migration by directly targeting CBL

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