scholarly journals TRIM3 Facilitates Estrogen Signaling and Modulates Breast Cancer Cell Progression

2021 ◽  
Author(s):  
Beibei Wang ◽  
Xiaojing Tan ◽  
Le Wu ◽  
Peng Su ◽  
Xin Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Real Time ◽  
Rna Sequencing ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Endocrine Resistance ◽  
Estrogen Signaling ◽  
Clinical Issue ◽  
Er Alpha ◽  
Positive Breast Cancer

Abstract Background: Breast cancer ranks NO.1 in women cancer incidence worldwide, while 70% of breast cancers are estrogen receptor (ER) alpha positive. Compared with ER alpha negative breast cancer, which is more aggressive and shorter prognosis, ER alpha positive breast cancer could be well-controlled by endocrine therapy. Most of ER alpha positive breast cancer patients could benefit from selective ER alpha modulators, such as tamoxifen. However, approximately half of them will eventually develop endocrine resistance, making it an important clinical issue in breast cancer therapy. Thus, decoding the turnover of estrogen signaling, including the control of ER alpha expression and stability, are critical to the improvement of breast cancer therapeutics. Methods: TRIM3 and ER alpha protein expression levels were measured by western blot, while the ER alpha target genes were measured by real-time PCR. MTT assay was used to measure cell viability. RNA sequencing was analyzed by Ingenuity Pathway Analysis. Identification of ER alpha signaling was accomplished with luciferase assays, real-time RT-PCR and Western blotting. Protein stability assay and ubiquitin assay was used to detect ER alpha protein degradation. The ubiquitin-based Immuno-precipitation based assays were used to detect the specific ubiquitination manner happened on ER alpha. Results: In our current study, we identified TRIM3 as an E3 ligase, which promotes ER alpha signaling and breast cancer progression. TRIM3 depletion inhibits breast cancer cell proliferation and invasion, while the unbiased RNA sequencing data indicates that TRIM3 is required for the activation of estrogen signaling in whole genomic scale. Molecular studies show that TRIM3 associates with ER alpha and promotes ER alpha mono-ubiquitination. Conclusion: our study provides a novel post-translational mechanism in estrogen signaling. Modulation of TRIM3 expression or its function could be an interesting approach for breast cancer treatment.

scholarly journals TRIM3 inhibits P53 signaling in breast cancer cells

2020 ◽  
Author(s):  
Xinxing Wang ◽  
Yujie Zhang ◽  
Xinhong Pei ◽  
Guangcheng Guo ◽  
Bingjian Xue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Protein Localization ◽  
P53 Protein ◽  
P53 Signaling ◽  
Apoptosis Protein ◽  
Er Alpha ◽  
Positive Breast Cancer

Abstract BackgroundBeast cancer is the most common women cancer worldwide, while two third of them are ER alpha positive breast cancer. Among the ER alpha positive breast cancer, about 80% are P53 wild type, indicating the potential tumor suppression role in ER alpha positive breast cancer. Since P53 is an important safeguard to inhibit cell malignant transformation, reactivating P53 signaling could a plausible approach to treat breast cancer.MethodsTRIM3 protein levels were measured by western blot, while the P53 classical target genes were measured by real-time PCR. WST1 assay were used to measure cell proliferation, while cleaved caspase-3 was used to detect cell apoptosis. Protein stability and ubiquitin assay were used to detect the P53 protein ubiquitin and stability. The immuno-precipitation assays were used to detect the protein interactions. Immuno-staining was used to detect the protein localization of P53 and TRIM3, while the ubiquitin-based immuno-precipitation assays were used to detect the specific ubiquitination manner of P53.ResultsIn our study, we identified TRIM3 as an endogenous inhibitor for P53 signaling. TRIM3 depletion inhibited breast cancer cell proliferation and promoted apoptosis. In addition, TRIM3 depletion increased P53 protein level in breast cancer cell. Further investigation showed that TRIM3 could associate with P53 and promote P53 K48-linked ubiquitination and degradation.ConclusionOur study identified a novel post-translational modification mechanism between TRIM3 and P53. TRIM3 depletion or blockage could be a promising strategy to rescue P53 signaling and inhibit breast cancer progression.

scholarly journals ZNF213 facilitates ER alpha signaling in breast cancer cells

2020 ◽  
Author(s):  
Ting Zhuang ◽  
Huijie Yang ◽  
Wuchen Zhao ◽  
Xin Li ◽  
Zhiguo Niu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Stability ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Zinc Finger Protein ◽  
Endocrine Resistance ◽  
Luciferase Assay ◽  
Clinical Issue ◽  
Er Alpha ◽  
Positive Breast Cancer

Abstract Background Breast cancer is the most common women malignancy worldwide, while estrogen receptor alpha positive type accounts for two third of all breast cancers. Although ER alpha positive breast cancer could be effectively controlled by endocrine therapy, more than half of the cases could develop endocrine resistance, making it an important clinical issue in breast cancer treatment. Thus, decoding the detailed mechanism, which controls ER alpha signaling activation and ER alpha protein stability, is of great importance for the improvement of breast cancer therapy. Methods ZNF213 and ER alpha protein expression level were measured by western blot, while ER alpha target genes were determined by QPCR. WST-1 assay was used to measure cell proliferation. RNA sequence was performed by Ingenuity pathway analysis. The ER alpha signaling activities were measured with luciferase assay, QPCR and western blotting. Protein stability assay and ubiquitin assay were used to determine ER alpha protein degradation and ubiquitination. The immuno-precipation was utilized to determine ER alpha and ZNF213 interaction. The ubiquitin-based immuno-precipitation assay was sued to detect specific ubiquitination manner on ER alpha. The prognostic data of ZNF213 was derived from public available database. Results Here, we identified ZNF213 as a novel zinc finger protein, which modulates ER alpha protein. ZNF213 expression correlates with poor outcome in endocrine treated patients. ZNF213 depletion inhibits ER alpha signaling and proliferation in breast cancer cells. Further mechanistic studies show that ZNF213 is located in cytosol and nuclear, which modulates ER alpha stability via inhibiting ER alpha K48-linked ubiquitination. Conclusions Our study reveals an interesting post-translational mechanism between ER alpha and ZNF213 in breast cancer. Targeting ZNF213 could be an appealing strategy for ER alpha positive breast cancer.

scholarly journals ZNF213 Facilitates ER Alpha Signaling in Breast Cancer Cells

2020 ◽  
Author(s):  
Huijie Yang ◽  
Xulei Lv ◽  
Xin Li ◽  
Lanzhi Mao ◽  
Zhiguo Niu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Stability ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Zinc Finger Protein ◽  
Endocrine Resistance ◽  
Luciferase Assay ◽  
Clinical Issue ◽  
Er Alpha ◽  
Positive Breast Cancer

Abstract Background Breast cancer is the most common women malignancy worldwide, while estrogen receptor alpha positive type accounts for two third of all breast cancers. Although ER alpha positive breast cancer could be effectively controlled by endocrine therapy, more than half of the cases could develop endocrine resistance, making it an important clinical issue in breast cancer treatment. Thus, decoding the detailed mechanism, which controls ER alpha signaling activation and ER alpha protein stability, is of great importance for the improvement of breast cancer therapy. Methods CCK8 and Edu assay was used to measure cell proliferation. RNA sequence was performed by Ingenuity pathway analysis. The ER alpha signaling activities were measured with luciferase assay, QPCR and western blotting. Protein stability assay and ubiquitin assay were used to determine ER alpha protein degradation and ubiquitination. The immuno-precipitation was utilized to determine ER alpha and ZNF213 interaction. The ubiquitin-based immuno-precipitation assay was sued to detect specific ubiquitination manner on ER alpha. Results we identified ZNF213 as a novel zinc finger protein, which modulated ER alpha protein. ZNF213 expression correlated with poor outcome in endocrine treated patients. ZNF213 depletion inhibited ER alpha signaling and proliferation in breast cancer cells. Further mechanistic studies showed ZNF213 located in cytosol and nuclear, which modulated ER alpha stability via inhibiting ER alpha K48-linked ubiquitination. Conclusions Our study reveals an interesting post-translational mechanism between ER alpha and ZNF213 in breast cancer. Targeting ZNF213 could be an appealing strategy for ER alpha positive breast cancer.

scholarly journals TRIM3 inhibits P53 signaling in breast cancer cells

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xinxing Wang ◽  
Yujie Zhang ◽  
Xinhong Pei ◽  
Guangcheng Guo ◽  
Bingjian Xue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Protein Localization ◽  
P53 Protein ◽  
P53 Signaling ◽  
Apoptosis Protein ◽  
Er Alpha ◽  
Positive Breast Cancer

Abstract Background Beast cancer is the most common women cancer worldwide, while two third of them are ER alpha positive breast cancer. Among the ER alpha positive breast cancer, about 80% are P53 wild type, indicating the potential tumor suppression role in ER alpha positive breast cancer. Since P53 is an important safeguard to inhibit cell malignant transformation, reactivating P53 signaling could a plausible approach to treat breast cancer. Methods TRIM3 protein levels were measured by western blot, while the P53 classical target genes were measured by real-time PCR. WST1 assay were used to measure cell proliferation, while cleaved caspase-3 was used to detect cell apoptosis. Protein stability and ubiquitin assay were used to detect the P53 protein ubiquitin and stability. The immuno-precipitation assays were used to detect the protein interactions. Immuno-staining was used to detect the protein localization of P53 and TRIM3, while the ubiquitin-based immuno-precipitation assays were used to detect the specific ubiquitination manner of P53. Results In our study, we identified TRIM3 as an endogenous inhibitor for P53 signaling. TRIM3 depletion inhibited breast cancer cell proliferation and promoted apoptosis. In addition, TRIM3 depletion increased P53 protein level in breast cancer cell. Further investigation showed that TRIM3 could associate with P53 and promote P53 K48-linked ubiquitination and degradation. Conclusion Our study identified a novel post-translational modification mechanism between TRIM3 and P53. TRIM3 depletion or blockage could be a promising strategy to rescue P53 signaling and inhibit breast cancer progression.

scholarly journals TRIM3 inhibits P53 signaling in breast cancer cells

2020 ◽  
Author(s):  
Xinxing Wang ◽  
Yujie Zhang ◽  
Xinhong Pei ◽  
Guangcheng Guo ◽  
Bingjian Xue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Protein Localization ◽  
P53 Protein ◽  
P53 Signaling ◽  
Apoptosis Protein ◽  
Er Alpha ◽  
Positive Breast Cancer

Abstract Background: Beast cancer is the most common women cancer worldwide, while two third of them are ER alpha positive breast cancer. Among the ER alpha positive breast cancer, about 80% are P53 wild type, indicating the potential tumor suppression role in ER alpha positive breast cancer. Since P53 is an important safeguard to inhibit cell malignant transformation, reactivating P53 signaling could a plausible approach to treat breast cancer. Methods: TRIM3 protein levels were measured by western blot, while the P53 classical target genes were measured by real-time PCR. WST1 assay were used to measure cell proliferation, while cleaved caspase-3 was used to detect cell apoptosis. Protein stability and ubiquitin assay were used to detect the P53 protein ubiquitin and stability. The immuno-precipitation assays were used to detect the protein interactions. Immuno-staining was used to detect the protein localization of P53 and TRIM3, while the ubiquitin-based immuno-precipitation assays were used to detect the specific ubiquitination manner of P53. Results: In our study, we identified TRIM3 as an endogenous inhibitor for P53 signaling. TRIM3 depletion inhibited breast cancer cell proliferation and promoted apoptosis. In addition, TRIM3 depletion increased P53 protein level in breast cancer cell. Further investigation showed that TRIM3 could associate with P53 and promote P53 K48-linked ubiquitination and degradation.Conclusion: Our study identified a novel post-translational modification mechanism between TRIM3 and P53. TRIM3 depletion or blockage could be a promising strategy to rescue P53 signaling and inhibit breast cancer progression.

scholarly journals TRIM3 inhibits P53 signaling in breast cancer cells

2020 ◽  
Author(s):  
Xinxing Wang ◽  
Yujie Zhang ◽  
Xinhong Pei ◽  
Guangcheng Guo ◽  
Bingjian Xue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Protein Localization ◽  
P53 Protein ◽  
P53 Signaling ◽  
Apoptosis Protein ◽  
Er Alpha ◽  
Positive Breast Cancer

Abstract BackgroundBeast cancer is the most common women cancer worldwide, while two third of them are ER alpha positive breast cancer. Among the ER alpha positive breast cancer, about 80% are P53 wild type, indicating the potential tumor suppression role in ER alpha positive breast cancer. Since P53 is an important safeguard to inhibit cell malignant transformation, reactivating P53 signaling could a plausible approach to treat breast cancer.MethodsTRIM3 protein levels were measured by western blot, while the P53 classical target genes were measured by real-time PCR. WST1 assay were used to measure cell proliferation, while cleaved caspase-3 was used to detect cell apoptosis. Protein stability and ubiquitin assay were used to detect the P53 protein ubiquitin and stability. The immuno-precipitation assays were used to detect the protein interactions. Immuno-staining was used to detect the protein localization of P53 and TRIM3, while the ubiquitin-based immuno-precipitation assays were used to detect the specific ubiquitination manner of P53.ResultsIn our study, we identified TRIM3 as an endogenous inhibitor for P53 signaling. TRIM3 depletion inhibited breast cancer cell proliferation and promoted apoptosis. In addition, TRIM3 depletion increased P53 protein level in breast cancer cell. Further investigation showed that TRIM3 could associate with P53 and promote P53 K48-linked ubiquitination and degradation.ConclusionOur study identified a novel post-translational modification mechanism between TRIM3 and P53. TRIM3 depletion or blockage could be a promising strategy to rescue P53 signaling and inhibit breast cancer progression.Highlights1. TRIM3 facilitates breast cancer cell growth and anti-apotosis.2. TRIM3 inhibits P53 protein and its signaling activity.3. TRIM3 interacts with P53 and promotes P53 K48-linked ubiquitination and degradation.

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