Methylation‐mediated miR‐214 regulates proliferation and drug sensitivity of renal cell carcinoma cells through targeting LIVIN

Xu, Hao; Wu, Shangjun; Shen, Xin; Shi, Zhan; Wu, Duojie; Yuan, Yuan; Jiang, Wei; Wang, Qianliang; Qin, Ke; Mao, Qing; Li, Xianlong; Liu, Yong; Yuan, Pingcheng; Zhang, Qinghan; Huang, Enying; Chen, Xiaogang

doi:10.1111/jcmm.15287

Cited by 13 publications

(7 citation statements)

References 29 publications

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“…Also, miR-214 has been shown to inhibit proliferation of RCC cells through reduction in expression levels of Insulin-like Growth Factor-1 (IGF-1) Receptor and inhibition of downstream mTORC1 signaling, regardless of VHL status [ 38 ]. Conversely, low expression levels of miR-214 were associated with enhanced cell growth and reduced drug sensitivity in RCC cells [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

A “Lymphocyte MicroRNA Signature” as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming

Incorvaia

Fanale

Badalamenti

et al. 2020

Cancers

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Introduction of checkpoint inhibitors resulted in durable responses and improvements in overall survival in advanced RCC patients, but the treatment efficacy is widely variable, and a considerable number of patients are resistant to PD-1/PD-L1 inhibition. This variability of clinical response makes necessary the discovery of predictive biomarkers for patient selection. Previous findings showed that the epigenetic modifications, including an extensive microRNA-mediated regulation of tumor suppressor genes, are key features of RCC. Based on this biological background, we hypothesized that a miRNA expression profile directly identified in the peripheral lymphocytes of the patients before and after the nivolumab administration could represent a step toward a real-time monitoring of the dynamic changes during cancer evolution and treatment. Interestingly, we found a specific subset of miRNAs, called “lymphocyte miRNA signature”, specifically induced in long-responder patients (CR, PR, or SD to nivolumab >18 months). Focusing on the clinical translational potential of miRNAs in controlling the expression of immune checkpoints, we identified the association between the plasma levels of soluble PD-1/PD-L1 and expression of some lymphocyte miRNAs. These findings could help the development of novel dynamic predictive biomarkers urgently needed to predict the potential response to immunotherapy and to guide clinical decision-making in RCC patients.

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Section: Discussionmentioning

confidence: 99%

A “Lymphocyte MicroRNA Signature” as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming

Incorvaia

Fanale

Badalamenti

et al. 2020

Cancers

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“…A number of functional studies have revealed deregulated miRNA (either upregulation or downregulation) involved in cell cycle regulation, apoptosis, cell adhesion, and extracellular matrix or metabolism with a key role in RCC [ 111 , 135 , 136 , 137 ]. In this sense, miR-21 is silenced by promoter methylation in RCC, and its expression inhibits RCC growth through regulating LIVIN, a member of the inhibitor of apoptosis proteins [ 138 ].…”

Section: Epigenetics Of Clear Cell Renal Cell Carcinomamentioning

confidence: 99%

The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments

Angulo

Manini

López

et al. 2021

Cancers

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Clear cell renal cell carcinoma (ccRCC) is curable when diagnosed at an early stage, but when disease is non-confined it is the urologic cancer with worst prognosis. Antiangiogenic treatment and immune checkpoint inhibition therapy constitute a very promising combined therapy for advanced and metastatic disease. Many exploratory studies have identified epigenetic markers based on DNA methylation, histone modification, and ncRNA expression that epigenetically regulate gene expression in ccRCC. Additionally, epigenetic modifiers genes have been proposed as promising biomarkers for ccRCC. We review and discuss the current understanding of how epigenetic changes determine the main molecular pathways of ccRCC initiation and progression, and also its clinical implications. Despite the extensive research performed, candidate epigenetic biomarkers are not used in clinical practice for several reasons. However, the accumulated body of evidence of developing epigenetically-based biomarkers will likely allow the identification of ccRCC at a higher risk of progression. That will facilitate the establishment of firmer therapeutic decisions in a changing landscape and also monitor active surveillance in the aging population. What is more, a better knowledge of the activities of chromatin modifiers may serve to develop new therapeutic opportunities. Interesting clinical trials on epigenetic treatments for ccRCC associated with well established antiangiogenic treatments and immune checkpoint inhibitors are revisited.

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“… 8 For instance, miR-214 repressed the growth of renal cell carcinoma cell in vitro and in vivo through targeting LIVIN. 9 Moreover, miR-214-3p was downregulated in hepatocellular carcinoma tissues versus normal liver tissues, and poor miR-214-3p expression was linked to shorter overall survival rate and recurrence-free survival of hepatocellular carcinoma patients. 10 Nevertheless, no researches concentrated on the relevance of miR-214 in CSCC.…”

Section: Introductionmentioning

confidence: 98%

microRNA-214 Prevents Traits of Cutaneous Squamous Cell Carcinoma via VEGFA and Bcl-2

Zhang

et al. 2020

Technol Cancer Res Treat

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Background: Dysregulation of microRNA-214 (miR-214) has been indicated in different tumors. The function of miR-214 in cutaneous squamous cell carcinoma (CSCC) is yet to be deciphered. The current study aimed to investigate the specific mechanism underpinning CSCC development with the involvement of miR-214 and its putative targets. Methods: Microarray analysis of CSCC and adjacent tissues was carried out to filter the most significant downregulated miRNA. Survival analysis of patients was subsequently implemented, followed by miRNA expression determination in CSCC cells. Gain-of-function assays were performed to evaluate its function on cellular level. The targets of the determined miRNA were predicted and their expression in CSCC and adjacent tissues was evaluated. The targeting relationship was analyzed by dual-luciferase assays. Finally, rescue experiments were conducted. Results: miR-214 was reduced in CSCC tissues and cells, and the survival of patients harboring overexpression of miR-214 was higher. miR-214 restoration increased CSCC cell apoptosis, while decreased proliferative, invasive and migratory activities. miR-214 interacted with vascular endothelial growth factor A (VEGFA) and B-cell CLL/lymphoma 2 (Bcl-2). VEGFA and Bcl-2, overexpressed in CSCC tissues and cells, were negatively correlated with miR-214. Moreover, VEGFA and Bcl-2 overexpression reversed the anti-tumor phenotypes of miR-214 on CSCC cells. miR-214 disrupted the Wnt/β-catenin pathway through VEGFA and Bcl-2 in the CSCC cells. Conclusion: Our data demonstrates that miR-214 exerts a suppressing role in CSCC. The discovery of novel targets such as miR-214 and VEGFA/Bcl-2 may facilitate the development of therapeutic options.

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Methylation‐mediated miR‐214 regulates proliferation and drug sensitivity of renal cell carcinoma cells through targeting LIVIN

Cited by 13 publications

References 29 publications

A “Lymphocyte MicroRNA Signature” as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming

A “Lymphocyte MicroRNA Signature” as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming

The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments

microRNA-214 Prevents Traits of Cutaneous Squamous Cell Carcinoma via VEGFA and Bcl-2

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