A DAAM1 3′-UTR SNP mutation regulates breast cancer metastasis through affecting miR-208a-5p-DAAM1-RhoA axis

Mei, Jie; Yan, Ting; Huang, Yi-Fu; Xia, Tiansong; Fei, Chang; Shen, Shuning; Hao, Lijun; Chen, Yin; Wang, Zhongyuan; Jiang, Xiaozheng; Xu, Bujie; Zhu, Yichao

doi:10.1186/s12935-019-0747-8

Cited by 27 publications

(19 citation statements)

References 25 publications

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“…To further assess the association between the expression of these hub genes and the risk of breast cancer metastasis, we employed KM Plotter to evaluate the prognostic value of these genes in DMFS. The primary purpose of KM Plotter is to evaluate potential biomarkers in a meta-analysisbased manner, and many prognostic biomarkers have been identified based on this platform [51][52][53]. Five hub genes, including TPX2, KIF2C, CDCA8, BUB1B, and CCNA2, were validated to be notably associated with the shorter DMFS of breast cancer in the patient cohort based on KM Plotter.…”

Section: Discussionmentioning

confidence: 99%

Identification of five hub genes as monitoring biomarkers for breast cancer metastasis in silico

et al. 2019

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Background: Breast cancer is one of the most common endocrine cancers among females worldwide. Distant metastasis of breast cancer is causing an increasing number of breast cancer-related deaths. However, the potential mechanisms of metastasis and candidate biomarkers remain to be further explored. Results: The gene expression profiles of GSE102484 were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to screen for the most potent gene modules associated with the metastatic risk of breast cancer, and a total of 12 modules were identified based on the analysis. In the most significant module (R 2 = 0.68), 21 network hub genes (MM > 0.90) were retained for further analyses. Next, protein-protein interaction (PPI) networks were used to further explore the biomarkers with the most interactions in gene modules. According to the PPI networks, five hub genes (TPX2, KIF2C, CDCA8, BUB1B, and CCNA2) were identified as key genes associated with breast cancer progression. Furthermore, the prognostic value and differential expression of these genes were validated based on data from The Cancer Genome Atlas (TCGA) and Kaplan-Meier (KM) Plotter. Receiver operating characteristic (ROC) curve analysis revealed that the mRNA expression levels of these five hub genes showed excellent diagnostic value for breast cancer and adjacent tissues. Moreover, these five hub genes were significantly associated with worse distant metastasis-free survival (DMFS) in the patient cohort based on KM Plotter. Conclusion: Five hub genes (TPX2, KIF2C, CDCA8, BUB1B, and CCNA2) associated with the risk of distant metastasis were extracted for further research, which might be used as biomarkers to predict distant metastasis of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Identification of five hub genes as monitoring biomarkers for breast cancer metastasis in silico

et al. 2019

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“… 21 SNPs in UTRs may influence the stability of mRNA, thus affecting the expression and activity of the enzyme. 42 , 43 According to a study identifying the potential SNPs related to miRNA, rs15524 may influence the hsa-miR-500a-5p that targets CYP3A5 , affecting its expression. 44 In addition, studies have found that CYP3A5*1D influences the pharmacokinetics of many drugs, including tacrolimus 45 and carbamazepine.…”

Section: Discussionmentioning

confidence: 99%

Association of CYP3A5 Gene Polymorphisms and Amlodipine-Induced Peripheral Edema in Chinese Han Patients with Essential Hypertension

Liang

Zhang

et al. 2021

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Background Amlodipine is one of the most used members of calcium channel blockers (CCB), available to treat hypertension. It is mainly metabolized by the Cytochrome P450 3A4/5 (CYP3A4/5) in the liver. Peripheral edema emerges as the major adverse drug reaction to amlodipine and is the primary reason for discontinuation of amlodipine therapy. However, genetic changes in CYP3A5 may lead to changes in the tolerability of amlodipine. Purpose In this study, we were interested whether variants in CYP3A5 have a role to play in amlodipine-induced peripheral edema. Methods A total number of 240 Chinese Han patients that have experienced hypertension were included in the study. Sixty-four patients had experienced amlodipine-induced peripheral edema, while the remaining 176 patients with no history of edema formed the control group. Twenty-four single-nucleotide polymorphisms (SNPs) of CYP3A5 gene were sequenced by targeted region sequencing method. The relationship of these genetic variants with amlodipine-induced peripheral edema risk was assessed using logistic regression. Results The allele frequencies of CYP3A5*1D (rs15524), CYP3A5*1E (rs4646453) and CYP3A5*3 (rs776746) were significantly different between cases and controls ( P <0.05). The CYP3A5 *3/*3 (CC) or CYP3A5 *1D/*1D (AA) carriers showed an increased risk of amlodipine-induced peripheral edema in dominant model. Meanwhile, patients carrying CYP3A5 *1E (AC/AA) showed a reduced risk of peripheral edema. Furthermore, we found a strong linkage disequilibrium among rs15524, rs4646453 and rs776746. Conclusion Our study reveals for the first time that CYP3A5 *1D, *1E and *3 were associated with amlodipine-induced peripheral edema in Chinese Han patients with hypertension. However, further studies comprising larger number of samples, more related genes and other factors are wanted.

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“…ab101512, Abcam) was used to visualize UBE3C expression. Previously described quantitative evaluation criteria were used [ 13 , 14 ]. Briefly, the percentage of positively stained cells was scored on a 0–4 scale: 0 (< 5%), 1 (6–25%), 2 (26–50%), 3 (51–75%) and 4 (> 75%).…”

Section: Methodsmentioning

confidence: 99%

Oncogenic UBE3C promotes breast cancer progression by activating Wnt/β-catenin signaling

et al. 2021

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Background Breast cancer (BrCa) is the most common female malignancy worldwide and has the highest morbidity among all cancers in females. Unfortunately, the mechanisms of BrCa growth and metastasis, which lead to a poor prognosis in BrCa patients, have not been well characterized. Methods Immunohistochemistry (IHC) was performed on a BrCa tissue microarray (TMA) containing 80 samples to evaluate ubiquitin protein ligase E3C (UBE3C) expression. In addition, a series of cellular experiments were conducted to reveal the role of UBE3C in BrCa. Results In this research, we identified UBE3C as an oncogenic factor in BrCa growth and metastasis for the first time. UBE3C expression was upregulated in BrCa tissues compared with adjacent breast tissues. BrCa patients with high nuclear UBE3C expression in tumors showed remarkably worse overall survival (OS) than those with low nuclear expression. Knockdown of UBE3C expression in MCF-7 and MDA-MB-453 BrCa cells inhibited cell proliferation, migration and invasion in vitro, while overexpression of UBE3C in these cells exerted the opposite effects. Moreover, UBE3C promoted β-catenin nuclear accumulation, leading to the activation of the Wnt/β-catenin signaling pathway in BrCa cells. Conclusion Collectively, these results imply that UBE3C plays crucial roles in BrCa development and progression and that UBE3C may be a novel target for the prevention and treatment of BrCa.

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A DAAM1 3′-UTR SNP mutation regulates breast cancer metastasis through affecting miR-208a-5p-DAAM1-RhoA axis

Cited by 27 publications

References 25 publications

Identification of five hub genes as monitoring biomarkers for breast cancer metastasis in silico

Identification of five hub genes as monitoring biomarkers for breast cancer metastasis in silico

Association of CYP3A5 Gene Polymorphisms and Amlodipine-Induced Peripheral Edema in Chinese Han Patients with Essential Hypertension

Oncogenic UBE3C promotes breast cancer progression by activating Wnt/β-catenin signaling

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