Greater expression of TC21/R‐ras2 in highly aggressive malignant skin cancer

Lee, Jang Hyun; Pyon, Jai-Kyung; Lee, Sang‐Han; Lee, Yoon Jin; Kang, Sang Gue; Kim, Chul Han; Kim, Dong Wook; Nam, Heerim; Park, Yoon Hyung; Jeong, Dong Jun; Cho, Moon Kyun

doi:10.1111/j.1365-4632.2010.04846.x

Cited by 22 publications

(19 citation statements)

References 12 publications

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“…RRAS2 has been shown to mediate transformation and cell survival via the activation of Phosphatidylinositol-3-kinase and Nuclear factor κB [55]. Interestingly, expression of RRAS2 is highly correlated with the aggressiveness of malignant skin cancers and a UV-mediated regulation is suggested in human tumorigenic prostate cells [56], [57].…”

Section: Resultsmentioning

confidence: 99%

UVA and UVB Irradiation Differentially Regulate microRNA Expression in Human Primary Keratinocytes

et al. 2013

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MicroRNA (miRNA)-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB. However, each wavelength band also activated a distinct subset of miRNAs. Common sets of UVA- and UVB-regulated miRNAs harbor the regulatory elements GLYCA-nTRE, GATA-1-undefined-site-13 or Hox-2.3-undefined-site-2 in their promoters. In silico analysis indicates that the differentially expressed miRNAs responding to UV have potential functions in the cellular pathways of cell growth and proliferation. Interestingly, the expression of miR-23b, which is a differentiation marker of human keratinocytes, is remarkably up-regulated after UVA irradiation. Studying the interaction between miR-23b and its putative skin-relevant targets using a Luciferase reporter assay revealed that RRAS2 (related RAS viral oncogene homolog 2), which is strongly expressed in highly aggressive malignant skin cancer, to be a direct target of miR-23b. This study demonstrates for the first time a differential miRNA response to UVA and UVB in human primary keratinocytes. This suggests that selective regulation of signaling pathways occurs in response to different UV energies. This may shed new light on miRNA-regulated carcinogenic processes involved in UV-induced skin carcinogenesis.

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Section: Resultsmentioning

confidence: 99%

UVA and UVB Irradiation Differentially Regulate microRNA Expression in Human Primary Keratinocytes

et al. 2013

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“…Univariate and multivariate analyses were based on the Cox proportional hazards regression model. To evaluate the amount of protein expression, the Raytest TINA software (http://www.raytest.de/service/raytest_catalog.html) was used for the densitometric analysis in the western blot assay as described previously [21]. P < 0.05 was considered statistically significant.…”

Section: Methodsmentioning

confidence: 99%

The Sirtuin 3 Expression Profile Is Associated with Pathological and Clinical Outcomes in Colon Cancer Patients

Liu

Huang

Jiang

et al. 2014

BioMed Research International

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Aim. To investigate the correlation between Sirtuin 3 (SIRT3) expression and the clinical outcome of patients with colon cancer. Methods. The tumor specimens from 127 patients with colon cancer were obtained for SIRT3 immunohistochemical staining. Patients were followed up. In in vitro study, SIRT3 gene was inhibited to observe the effects of SIRT3 on the biological behavior of cultured colon cells. Results. The SIRT3 expression level was found to be significantly associated with the lymph node metastasis (P < 0.001) and tumor stages (P < 0.001). The colon cancer-specific survival was 64.6% among patients with high SIRT3 expressions and 88.6% among patients with low SIRT3 expressions (log-rank P = 0.016). The overall survival was 80.2% among patients with low SIRT3 expressions and 55.9% among patients with high SIRT3 expressions (log-rank P = 0.002). In vitro study showed that silencing of SIRT3 gene inhibited the proliferation, invasion, and cells migration but increased the apoptosis in the cultured colon cell lines. Conclusion. This study provides evidence supporting that SIRT3 is closely associated with the clinical outcomes of colon cancer. SIRT3 may be considered as a marker for colon cancer.

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“…Here, we demonstrate that a Ras family protein, R-Ras2 (also called TC21 because it was cloned from a human teratocarcinoma cDNA library) (Drivas et al, 1990), which is able to transform cells and is up-regulated in several human cancers (Lee et al, 2011; Gutierrez-Erlandsson et al, 2013; Erdogan et al, 2007; Murphy et al, 2002), is regulated by a novel PTM, lysine fatty acylation. Importantly, SIRT6 is identified as the defatty-acylase of R-Ras2.…”

Section: Introductionmentioning

confidence: 95%

SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation

Zhang

Spiegelman

Nelson

et al. 2017

eLife

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The Ras family of GTPases are important in cell signaling and frequently mutated in human tumors. Understanding their regulation is thus important for studying biology and human diseases. Here, we report that a novel posttranslational mechanism, reversible lysine fatty acylation, regulates R-Ras2, a member of the Ras family. SIRT6, a sirtuin with established tumor suppressor function, regulates the lysine fatty acylation of R-Ras2. In mouse embryonic fibroblasts (MEFs), Sirt6 knockout (KO) increased R-Ras2 lysine fatty acylation. Lysine fatty acylation promotes the plasma membrane localization of R-Ras2 and its interaction with phosphatidylinositol 3-kinase PI3K, leading to activated Akt and increased cell proliferation. Our study establishes lysine fatty acylation as a previously unknown mechanism that regulates the Ras family of GTPases and provides an important mechanism by which SIRT6 functions as a tumor suppressor.DOI: http://dx.doi.org/10.7554/eLife.25158.001

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Greater expression of TC21/R‐ras2 in highly aggressive malignant skin cancer

Abstract: This article is the first study demonstrating expression of TC21 in human skin malignant tumors and suggests that TC21 is more expressed in highly aggressive skin tumors.

Cited by 22 publications

References 12 publications

UVA and UVB Irradiation Differentially Regulate microRNA Expression in Human Primary Keratinocytes

UVA and UVB Irradiation Differentially Regulate microRNA Expression in Human Primary Keratinocytes

The Sirtuin 3 Expression Profile Is Associated with Pathological and Clinical Outcomes in Colon Cancer Patients

SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation

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