SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c‑JUN

Yao, Yang; Liang, Yanhua; Zheng, Yan; Tang, Ling‑Jie; Zhou, Sitong; Zhu, Jingna

doi:10.3892/mmr.2020.10981

Cited by 3 publications

(3 citation statements)

References 75 publications

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“…The c-Jun transcription factor was the first oncogenic transcription factor discovered, and is the cellular homologue of v-Jun [ 44 ]. Studies have found that c-Jun with physiological functions can promote embryonic liver development and liver and skin regeneration [ 45 ]. Moreover, c-Jun is implicated in carcinogenesis and development of many tumors.…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis-Related Proteins Are Potential Diagnostic Molecular Markers for Patients with Preeclampsia

Shi

Yang

Ding

et al. 2022

Biology

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Preeclampsia (PE) is the leading cause of maternal and fetal mortality and morbidity. Early and accurate diagnosis is critical to reduce mortality. Placental oxidative stress has been identified as a major pathway to the development of PE. Ferroptosis, a new form of regulated cell death, is associated with iron metabolism and oxidative stress, and has been suspected to play a role in the pathophysiology of PE, although the mechanism is yet to be elucidated. The identification of potential ferroptosis-related biomarkers is of great significance for the early diagnosis and treatment of PE. A gene expression dataset of peripheral blood samples was downloaded from the Gene Expression Omnibus (GEO) dataset. Differentially expressed genes (DEGs) were filtrated with the R package “limma”. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the DEGs were then conducted. Ferroptosis-related DEGs were screened by overlapping the ferroptosis-related genes with DEGs. The protein–protein interaction (PPI) network was used to identify the key ferroptosis-related DEGs. Enzyme-linked immunosorbent assay (ELISA) was used to validate changes in the selected key ferroptosis-related DEGs. The correlations between the key genes and clinical and pathological characteristics were analyzed. Finally, the diagnostic value of these key genes for PE was confirmed by a receiver operating characteristic (ROC) curve. A total of 5913 DEGs were identified and 45 ferroptosis-related DEGs were obtained. Besides, ferroptosis-related pathways were enriched by KEGG using DEGs. The PPI network showed that p53 and c-Jun were the critical hub genes. ELISA showed that p53 in the serum of PE patients was higher than that of the control group, while c-Jun was lower than that of the control group. Analysis of the clinicopathological features showed that p53 and c-Jun were correlated with the PE characteristics. Finally, based on the area under curve (AUC) values, c-Jun had the superior diagnostic power (AUC = 0.87, p < 0.001), followed by p53 (AUC = 0.75, p < 0.001). Our study identified that two key genes, p53 and c-Jun, might be potential diagnostic biomarkers of PE.

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Section: Discussionmentioning

confidence: 99%

Ferroptosis-Related Proteins Are Potential Diagnostic Molecular Markers for Patients with Preeclampsia

Shi

Yang

Ding

et al. 2022

Biology

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“…There are three major types of skin cancers: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. SHARPIN is downregulated or absent and highly mutated in cancer nests and precancerous BCC and SCC lesions compared with normal skin samples [ 134 , 135 ]. Knockdown of SHARPIN in TE354.T cells, a human BCC cell line, enhanced tumor cell proliferation, possibly due to the increased phosphorylation of two transcriptional factors, c‑JUN and GLI family zinc finger 2 (GLI2) [ 134 ].…”

Section: Introductionmentioning

confidence: 99%

“…SHARPIN is downregulated or absent and highly mutated in cancer nests and precancerous BCC and SCC lesions compared with normal skin samples [ 134 , 135 ]. Knockdown of SHARPIN in TE354.T cells, a human BCC cell line, enhanced tumor cell proliferation, possibly due to the increased phosphorylation of two transcriptional factors, c‑JUN and GLI family zinc finger 2 (GLI2) [ 134 ]. By contrast, higher expression of SHARPIN correlates with worse survival of melanoma [ 119 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery

Li,

Liu,

2023

Cell Commun Signal

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Linear ubiquitination is a distinct type of ubiquitination that involves attaching a head-to-tail polyubiquitin chain to a substrate protein. Early studies found that linear ubiquitin chains are essential for the TNFα- and IL-1-mediated NF-κB signaling pathways. However, recent studies have discovered at least sixteen linear ubiquitination substrates, which exhibit a broader activity than expected and mediate many other signaling pathways beyond NF-κB signaling. Dysregulation of linear ubiquitination in these pathways has been linked to many types of cancers, such as lymphoma, liver cancer, and breast cancer. Since the discovery of linear ubiquitin, extensive effort has been made to delineate the molecular mechanisms of how dysregulation of linear ubiquitination causes tumorigenesis and cancer development. In this review, we highlight newly discovered linear ubiquitination-mediated signaling pathways, recent advances in the role of linear ubiquitin in different types of cancers, and the development of linear ubiquitin inhibitors.

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A functional variant of SHARPIN confers increased risk of late-onset Alzheimer’s disease

et al. 2021

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Late-onset Alzheimer’s disease (LOAD) is the most common form of dementia, and its pathogenesis is multifactorial. We previously reported a rare functional variant of SHARPIN (rs572750141, NP_112236.3:p.Gly186Arg) that was significantly associated with LOAD. In addition, several recent studies have suggested the potential role of SHARPIN in AD pathogenesis. In this study, we sought to identify additional functional variants of SHARPIN in Japanese population. Six highly deleterious variants of SHARPIN, comprising four missense variants, one frameshift variant, and one stop-gain variant were detected from whole-genome sequencing data for 180 patients with LOAD and 184 with mild cognitive impairment. One of these candidate variants (rs77359862, NP_112236.3:p.Arg274Trp) was significantly associated with an increased risk of LOAD in 5043 LOAD cases and 11984 controls (P = 0.0016, odds ratio = 1.43). Furthermore, this variant SHARPIN showed aberrant cellular localization and reduced the activation of NF-κB, a central mediator of inflammatory and immune responses. Further investigation of the physiologic role of SHARPIN may reveal the mechanism of onset of LOAD.

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SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c‑JUN

Cited by 3 publications

References 75 publications

Ferroptosis-Related Proteins Are Potential Diagnostic Molecular Markers for Patients with Preeclampsia

Ferroptosis-Related Proteins Are Potential Diagnostic Molecular Markers for Patients with Preeclampsia

Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery

A functional variant of SHARPIN confers increased risk of late-onset Alzheimer’s disease

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