Clinical significance of ring finger protein 2 high expression in skin squamous cell carcinoma

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Abstract

Although ring finger protein 2 (RNF2) serves an important role in the occurrence, development and regulation of various types of cancer, RNF2 expression in skin squamous cell carcinoma (SCC) remains unknown. The aim of the present study was to investigate the role of RNF2 expression in SCC and adjacent tissues from patients. The protein and gene expression levels of RNF2 in SCC and adjacent tissues were detected by immunohistochemistry (IHC), western blot analysis and semi-quantitative reverse transcription (RT) PCR. Single factor analysis was used to study the association between RNF2 expression level and the clinicopathological characteristics of patients with SCC. Multifactor Cox survival analysis was used to examine the association between RNF2 expression and the overall survival rate of postoperative patients with SCC. The results from IHC staining demonstrated that the positive expression rate of RNF2 was 84.68% (210/248) and 56.05% (139/248) in SCC and in adjacent tissues, respectively. Furthermore, results from western blot analysis demonstrated that RNF2 protein expression in SCC tissues was significantly higher compared with that in the adjacent tissues (P<0.05). The positive rate of RNF2 mRNA in SCC was 81.05% (201/248), which was significantly higher compared with that in the adjacent tissues 54.44% (135/248; P<0.05). Furthermore, RNF2 protein and gene expression levels were associated with tumor diameter, tumor stage, tumor metastasis and the degree of tumor differentiation in patients with SCC. Patients exhibiting higher RNF2 protein expression in SCC tissues had a significantly shorter disease-specific survival rate compared with patients with low RNF2 expression. In addition, RNF2 protein expression, tumor diameter, tumors site and tumor stage were independent factors affecting the overall survival rate of postoperative patients. High protein and gene expression levels of RNF2 in SCC tissues may be associated with the occurrence and development of SCC and prognosis of patients. The results form this study may serve the development of novel therapeutic options and diagnostic strategies for patients with SCC.

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Interventions for non-metastatic squamous cell carcinoma of the skin: systematic review and pooled analysis of observational studies

Louise Lansbury, Fiona Bath-Hextall, William Perkins … (2013)

Objectives To assess the effects of treatments for non-metastatic invasive squamous cell carcinoma (SCC) of the skin using evidence from observational studies, given the paucity of evidence from randomised controlled trials. Design Systematic review of observational studies. Data sources Medline, Embase, to December 2012. Review methods Observational studies of interventions for primary, non-metastatic, invasive, SCC of the skin that reported recurrence during follow-up, quality of life, initial response to treatment, adverse events, cosmetic appearance, or death from disease. Studies were excluded if data for primary cutaneous SCC was not separable from other data. Data were extracted independently by two reviewers. Meta-analysis was performed where appropriate using a random effects model to estimate the pooled proportion of an event with 95% confidence intervals. Results 118 publications were included, covering seven treatment modalities. Pooled estimates of recurrence of SCCs were lowest after cryotherapy (0.8% (95% confidence interval 0.1% to 2%)) and curettage and electrodesiccation (1.7% (0.5% to 3.4%)), but most treated SCCs were small, low risk lesions. After Mohs micrographic surgery, the pooled estimate of local recurrence during variable follow-up periods from 10 studies was 3.0% (2.2% to 3.9%), which was non-significantly lower than the pooled average local recurrence of 5.4% (2.5% to 9.1%) after standard surgical excision (12 studies), and 6.4% (3.0% to 11.0%) after external radiotherapy (7 studies). After an apparently successful initial response of SCCs to photodynamic therapy, pooled average recurrence of 26.4% (12.3% to 43.7%; 8 studies) was significantly higher than other treatments. Evidence was limited for laser treatment (1 study) and for topical and systemic treatments (mostly single case reports or small non-comparative series with limited follow-up). Conclusions Many observational studies have looked at different treatment modalities for SCC, but the evidence base for the effectiveness of these interventions is poor. Comparison of outcomes after different treatments should be interpreted cautiously owing to biases inherent in the types of study included, and lack of direct comparisons to enable the estimation of relative treatment effect. Further evidence is needed to develop a prognostic model and stratify individuals at high risk of developing SCC, to improve the evidence base for this common cancer and to optimise clinical management. Protocol registration International Prospective Register of Systematic Reviews (PROSPERO) registration number CRD42011001450.

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Hypoxia induces TWIST-activated epithelial-mesenchymal transition and proliferation of pancreatic cancer cells in vitro and in nude mice.

Shi Chen, Jiang-Zhi Chen, Jia-Qiang Zhang … (2016)

The epithelial-mesenchymal transition (EMT) plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) development and progression. TWIST activated by intra-tumoral hypoxia functions to promote the EMT. We hypothesized that TWIST and the downstream gene pathway could mediate PDAC progression under hypoxia. Therefore, 90 PDAC tissue specimens were immunostained for TWIST and other proteins. Pancreatic cancer cell lines were used for in vitro experiments and nude mice were used to confirm the in vivo data. Expression of TWIST and HIF-1α proteins was significantly upregulated, whereas expression of E-cadherin and p16 was down-regulated in PDAC tissues compared to that of non-tumor tissues and in tumor tissues obtained from patients with tumor involving splenic artery than those without splenic artery involvement. Up-regulated TWIST in tumor tissues were associated with worse prognosis in PDAC patients. The in vitro data showed that HIF-1α-induced TWIST overexpression promoted tumor cell growth and EMT under a hypoxic condition via TWIST interaction with Ring1B and EZH2. In vivo data showed that TWIST overexpression or a hypoxic condition induce xenograft growth, abdominal metastasis and low mouse survival, whereas knockdown of either Ring1B or EZH2 expression suppressed tumor xenograft growth and metastasis and prolonged survival of nude mice. TWIST was the key player in promotion of pancreatic cancer development and metastasis under a hypoxic condition through interaction with Ring1B and EZH2 to regulate expression of E-cadherin and p16 proteins in pancreatic cancer cells.

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BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1

Sen Zhu, Dongyu Zhao, Lin Yan … (2018)

BMI1, a polycomb group (PcG) protein, plays a critical role in epigenetic regulation of cell differentiation and proliferation, and cancer stem cell self-renewal. BMI1 is upregulated in multiple types of cancer, including prostate cancer. As a key component of polycomb repressive complex 1 (PRC1), BMI1 exerts its oncogenic functions by enhancing the enzymatic activities of RING1B to ubiquitinate histone H2A at lysine 119 and repress gene transcription. Here, we report a PRC1-independent role of BMI1 that is critical for castration-resistant prostate cancer (CRPC) progression. BMI1 binds the androgen receptor (AR) and prevents MDM2-mediated AR protein degradation, resulting in sustained AR signaling in prostate cancer cells. More importantly, we demonstrate that targeting BMI1 effectively inhibits tumor growth of xenografts that have developed resistance to surgical castration and enzalutamide treatment. These results suggest that blocking BMI1 alone or in combination with anti-AR therapy can be more efficient to suppress prostate tumor growth.

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Author and article information

Journal

Journal ID (nlm-ta): Oncol Lett

Journal ID (iso-abbrev): Oncol Lett

Journal ID (publisher-id): OL

Title: Oncology Letters

Publisher: D.A. Spandidos

ISSN (Print): 1792-1074

ISSN (Electronic): 1792-1082

Publication date (Print): August 2020

Publication date (Electronic): 22 May 2020

Publication date PMC-release: 22 May 2020

Volume: 20

Issue: 2

Pages: 1111-1118

Affiliations

[1 ]Department of Pharmacy, The First People's Hospital of Yancheng City, Yancheng, Jiangsu 224005, P.R. China

[2 ]Department of Dermatology, Yancheng Hospital of Traditional Chinese Medicine, Affiliated to Nanjing University of Traditional Chinese Medicine, Yancheng, Jiangsu 224000, P.R. China

[3 ]Department of Clinical Laboratory, Linyi Traditional Hospital, Linyi, Shandong 276003, P.R. China

[4 ]Department of Laboratory Medicine, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu 214005, P.R. China

[5 ]Department of Laboratory Medicine, The First People's Hospital of Yancheng City, Yancheng, Jiangsu 224005, P.R. China

[6 ]Department of Laboratory Medicine, The Central Blood Station of Yancheng City, Yancheng, Jiangsu 224000, P.R. China

Author notes

Correspondence to: Dr Bin Liu, Department of Laboratory Medicine, The Fifth People's Hospital of Wuxi, 1215 Guangrui Road, Wuxi, Jiangsu 214005, P.R. China, E-mail: liubinwxr@ 123456126.com

Dr Bin Jiang, Department of Laboratory Medicine, The Central Blood Station of Yancheng City, 68 Xihuan Road, Yancheng, Jiangsu 224000, P.R. China, E-mail: jiangbin1612@ 123456163.com

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Publisher ID: OL-0-0-11666

DOI: 10.3892/ol.2020.11666

PMC ID: 7377046

SO-VID: 52500415-21f8-41dd-99e5-01d8fb892afb

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This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Clinical significance of ring finger protein 2 high expression in skin squamous cell carcinoma

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Karger: Oncology

Most cited references 31

Interventions for non-metastatic squamous cell carcinoma of the skin: systematic review and pooled analysis of observational studies

Hypoxia induces TWIST-activated epithelial-mesenchymal transition and proliferation of pancreatic cancer cells in vitro and in nude mice.

BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1

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