SHARPIN Facilitates p53 Degradation in Breast Cancer Cells

Yang, Huijie; Yu, Sifan; Wang, Weilong; Li, Xin; Hou, Yingxiang; Liu, Zhenhua; Shi, Yuanyuan; Mu, Kun; Niu, Gang; Xu, Juntao; Wang, Hui; Zhu, Jian; Zhuang, Ting

doi:10.1016/j.neo.2016.12.002

Cited by 43 publications

(50 citation statements)

References 47 publications

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“…After 24 hours, the cells were seeded with equal amount into 96‐well plate. The cell viability was determined by WST‐1 reagent, which was described in previous study …”

Section: Methodsmentioning

confidence: 99%

RNF168 facilitates proliferation and invasion of esophageal carcinoma, possibly via stabilizing STAT1

Xue

Wang

et al. 2018

J Cellular Molecular Medi

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Oesophageal cancer ranks as one of the most common malignancy in China and worldwide. Although genome‐wide association studies and molecular biology studies aim to elucidate the driver molecules in oesophageal cancer progression, the detailed mechanisms remain to be identified. Interestingly, RNF168 (RING finger protein 168) shows a high frequency of gene amplification in oesophageal cancer from TCGA database. Here, we report an important function for RNF168 protein in supporting oesophageal cancer growth and invasion by stabilizing STAT1 protein. RNF168 gene is amplified in oesophageal cancer samples, which tends to correlate with poor prognosis. Depletion RNF168 causes decreased cell proliferation and invasion in oesophageal cancer cells. Through unbiased RNA sequencing in RNF168 depleted oesophageal cancer cell, we identifies JAK‐STAT pathway is dramatically decreased. Depletion RNF168 reduced JAK‐STAT target genes, such as IRF1, IRF9 and IFITM1. Immuno‐precipitation reveals that RNF168 associates with STAT1 in the nucleus, stabilizing STAT1 protein and inhibiting its poly‐ubiquitination and degradation. Our study provides a novel mechanism that RNF168 promoting JAK‐STAT signalling in supporting oesophageal cancer progression. It could be a promising strategy to target RNF168 for oesophageal cancer treatment.

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“…After 24 hours, the cells were seeded with equal amount into 96‐well plate. The cell viability was determined by WST‐1 reagent, which was described in previous study …”

Section: Methodsmentioning

confidence: 99%

RNF168 facilitates proliferation and invasion of esophageal carcinoma, possibly via stabilizing STAT1

Xue

Wang

et al. 2018

J Cellular Molecular Medi

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“…a significant elevation of SHARPIN mRNA expression has been reported in breast cancer (46). SHarPin expression is associated with poor prognosis in patients with breast cancer (19,27). These studies reporting SHarPin overexpression have provided evidence of its function as an oncogene in the specific cancer types described above.…”

Section: Discussionmentioning

confidence: 80%

“…For example, Jung et al (26) demonstrated that SHarPin was upregulated in clear cell adenoma, hepatocellular carcinoma and papillary serous adenocarcinoma. additionally, several studies showed that SHarPin participated in the development of non-small cell lung cancer, melanoma, mycosis fungoides, breast cancer, prostate cancer and osteosarcoma (19,(27)(28)(29)(30)(31). Previous studies showed that the activation of the nF-κB pathway induced Sonic HH expression (32)(33)(34), and that uV light could also induce the activation of the nF-κB pathway during Bcc development (35)(36)(37).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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SHanK-associated rH domain-interacting protein (SHarPin) is a component of the linear ubiquitin chain assembly complex that can enhance the nF-κB and JnK signaling pathways, acting as a tumor-associated protein in a variety of cancer types. The present study investigated the role of SHarPin in cutaneous basal cell carcinoma (Bcc). Human Bcc (n=26) and normal skin (n=5) tissues, and Bcc (Te354.T) and normal skin (HacaT) cell lines were used to evaluate SHarPin expression level using immunohistochemistry and western blotting, respectively. a lentivirus carrying SHarPin-targeting or negative control short hairpin rna was infected into Te354.T cells, and the infected stable cells were assayed to analyze tumor cell proliferation, cell cycle, apoptosis, migration and invasion by cell counting Kit-8 and 5-ethynyl-2'-deoxyuridine incorporation assays, flow cytometry and Transwell assays. Western blotting was performed to assess the protein expression levels of gene signaling in SHarPin-silenced Bcc cells. SHarPin protein expression levels were downregulated or absent in Bcc cancer nests and precancerous lesions compared with normal skin samples. in addition, SHarPin expression levels were lower in Te354.T cells compared with HacaT cells. SHarPin shrna enhanced tumor cell proliferation and the S phase of the cell cycle, whereas Bcc cell apoptotic rates, and migratory and invasive abilities were not significantly altered. The expression levels of cyclin d1, cyclin-dependent kinase 4, phosphorylated-c-Jun and GLI family zinc finger 2 proteins were increased, whereas Patched 1 (PTcH1) and PTcH2 were decreased in the SHarPin-shrna-infected Bcc cells. Therefore, the present results suggested that SHarPin may act as a tumor suppressor during Bcc development. SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c-JUN

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“…After 24 hours, the cells were seeded into 96‐well plates. Cell numbers were determined using WST‐1 cell proliferation reagent as previously described …”

Section: Methodsmentioning

confidence: 99%

STAT1 facilitates oestrogen receptor α transcription and stimulates breast cancer cell proliferation

Hou

et al. 2018

J Cellular Molecular Medi

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Oestrogen receptor α (ERα) is overexpressed in two‐thirds of all breast cancer cases and is involved in breast cancer development and progression. Although ERα ‐positive breast cancer can be effectively treated by endocrine therapy, endocrine resistance is an urgent clinical problem. Thus, further understanding of the underlying mechanisms involved in ERα signalling is critical in dealing with endocrine resistance in patients with breast cancer. In the present study, unbiased RNA sequence analysis was conducted between the MCF‐7 and MCF‐7 tamoxifen‐resistant (LCC2) cell lines in order to identify differentially expressed genes. The whole transcriptomic data indicated that the JAK‐STAT pathway is markedly up‐regulated, particularly the ISGF3 complex. As the critical effectors, STAT1 and IRF9 were up‐regulated 5‐ and 20‐fold, respectively, in LCC2 cells. The biological experiments indicated that STAT1 is important for ERα signalling. Depletion of STAT1 or inhibition of STAT1 function significantly decreased levels of ERα protein, ERα ‐target gene expression and cell proliferation in both the MCF‐7 and LCC2 cell lines. Chromatin immunoprecipitation revealed that ERα transcription is associated with STAT1 recruitment to the ERα promoter region, suggesting that transcriptional regulation is one mechanism by which STAT1 regulates ERα mRNA levels and ERα signalling in breast cancer cells. The present study reveals a possible endocrine‐resistant mechanism by which STAT1 modulates ERα signalling and confers tamoxifen resistance. Targeting of STAT1 is a potential treatment strategy for endocrine‐resistant breast cancers.

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SHARPIN Facilitates p53 Degradation in Breast Cancer Cells

Cited by 43 publications

References 47 publications

RNF168 facilitates proliferation and invasion of esophageal carcinoma, possibly via stabilizing STAT1

RNF168 facilitates proliferation and invasion of esophageal carcinoma, possibly via stabilizing STAT1

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

STAT1 facilitates oestrogen receptor α transcription and stimulates breast cancer cell proliferation

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