Imbalance of the reciprocally inhibitory loop between the ubiquitin-specific protease USP43 and EGFR/PI3K/AKT drives breast carcinogenesis

He, Lin; Liu, Xinhua; Yang, Jianguo; Li, Wanjin; Liu, Shumeng; Liu, Xujun; Yang, Ziran; Ren, Jie; Wang, Yue; Lin, Shuo; Guan, Chengjian; Pei, Fei; Lei, Liandi; Zhang, Yu; Yi, Xin; Yang, Xiaohan; Liang, Jing; Liu, Rong; Sun, Luyang; Shang, Yongfeng

doi:10.1038/s41422-018-0079-6

Cited by 73 publications

(47 citation statements)

References 56 publications

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“…For Western blotting, membranes were incubated with appropriate antibodies for 1 hour at room temperature or overnight at 4°C followed by incubation with a secondary antibody. Immunoreactive bands were visualized using a Western blotting Luminol reagent (Santa Cruz Biotechnology) according to the manufacturer's recommendation (40).…”

Section: Immunoprecipitation and Western Blottingmentioning

confidence: 99%

Global crotonylome reveals CDYL-regulated RPA1 crotonylation in homologous recombination–mediated DNA repair

Liu

et al. 2020

Sci. Adv.

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105

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Previously, we reported that chromodomain Y-like (CDYL) acts as a crotonyl-coenzyme A hydratase and negatively regulates histone crotonylation (Kcr). However, the global CDYL-regulated crotonylome remains unclear. Here, we report a large-scale proteomics analysis for protein Kcr. We identify 14,311 Kcr sites across 3734 proteins in HeLa cells, providing by far the largest crotonylome dataset. We show that depletion of CDYL alters crotonylome landscape affecting diverse cellular pathways. Specifically, CDYL negatively regulated Kcr of RPA1, and mutation of the Kcr sites of RPA1 impaired its interaction with single-stranded DNA and/or with components of resection machinery, supporting a key role of RPA1 Kcr in homologous recombination DNA repair. Together, our study indicates that protein crotonylation has important implication in various pathophysiological processes. reveals CDYL-regulated RPA1 crotonylation in homologous recombination-mediated DNA repair.

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Section: Immunoprecipitation and Western Blottingmentioning

confidence: 99%

Global crotonylome reveals CDYL-regulated RPA1 crotonylation in homologous recombination–mediated DNA repair

Liu

et al. 2020

Sci. Adv.

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105

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“…The PI3K/Akt signaling pathway can be considered as a master regulator for cancer, 43 as it plays a vital role in BC translation, proliferation, growth, apoptosis, and cell differentiation. 44,45 Moreover, studies have shown that activated PPAR was involved in tumor promotion, cell differentiation, and apoptosis. By analyzing these biological processes and signaling pathways, we found that target genes may play a key role in the progression of BC.…”

Section: Discussionmentioning

confidence: 99%

Identification of prognostic biomarkers for breast cancer based on miRNA and mRNA co‐expression network

Yao

Liu

Gao

et al. 2019

J of Cellular Biochemistry

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Purpose Breast cancer (BC) remains a serious health threat for women due to its high incidence and the trend of rejuvenation. Accumulating evidence has highlighted that microRNAs (miRNAs) and messenger RNAs (mRNAs) could play important roles in various biological processes involved in the pathogenesis of BC. The present study aimed to identify potential prognostic biomarkers associated with BC. Methods Here, original gene expression profiles of patients with BC was downloaded from The Cancer Genome Atlas (TCGA) database. TargetScan, miRDB, and miRTarBase databases were used to predict the target genes of prognostic‐related differentially expressed miRNAs (DEMs). Subsequently, functional enrichment analysis and topological analysis were performed on the overlaps of target genes and differentially expressed mRNAs (DEGs), and Kaplan‐Meier analysis was used to predict prognosis‐related target genes to identify prognostic biomarkers. Results A total of 218 DEMs and 2222 DEGs were extracted in which eight miRNAs were associated with prognosis, and 278 target DEGs were screened out incorporated into functional enrichment analysis and protein‐protein interaction network visualization studies. Additionally, five hub genes (CXCL12, IGF1, LEF1, MMP1, and RACGAP1) were observed as potential biomarkers for BC prognosis through survival analysis. Conclusion We performed a distinctive correlation analysis of miRNA‐mRNA in BC patients, and identified eight miRNAs and five hub genes may be effective biomarkers for the prognosis of BC patients.

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“…Previous studies have demonstrated that EGFR leads to receptor tyrosine kinase autophosphorylation and further activated downstream intracellular signaling cascades especially the phosphatidylinositol 3kinase-AKT serine/threonine kinase 1 (PI3K-AKT) pathway, by binding with its cognate ligands [67,68].…”

Section: Lpp-as2 Decoys Mir-7-5p To Upregulate the Expression Of Egfrmentioning

confidence: 99%

Long noncoding RNA LPP-AS2 promotes glioma tumorigenesis via miR-7-5p/EGFR/PI3K/AKT/c-MYC feedback loop

Zhang¹,

Niu²,

Mu³

et al. 2020

Preprint

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Background: Glioblastoma is the most common primary malignant intracranial tumor with poor clinical prognosis in adults. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) function as important regulators in cancer progression, including glioblastoma. Here, we identified a new lncRNA LPP antisense RNA-2 (LPP-AS2) and investigated its function and mechanism in the development of glioma.Methods: High-throughput RNA sequencing was performed to discriminate differentially expressed lncRNAs and mRNAs between glioma tissues and normal brain tissues. Expression of LPP-AS2, epidermal growth factor receptor (EGFR) and miR-7-5p in glioma tissues and cell lines was detected by real-time quantitative PCR (RT-qPCR), and the functions of lncRNA LPP-AS2 in glioma were assessed by in vivo and in vitro assays. Insight into the underlying mechanism of competitive endogenous RNAs (ceRNAs) was obtained via bioinformatic analysis, dual luciferase reporter assays, RNA pulldown assays, RNA immunoprecipitation (RIP) and rescue experiments. Results: The results of high-throughput RNA-seq indicated lncRNA LPP-AS2 was upregulated in glioma tissues and further confirmed by RT-qPCR. Higher LPP-AS2 expression was related to a poor prognosis in glioma patients. Based on functional studies, LPP-AS2 depletion inhibited glioma cell proliferation, invasion and promoted apoptosis in vitro and restrained tumor growth in vivo, overexpression of LPP-AS2 resulted in the opposite effects. In addition, LPP-AS2 and EGFR were observed in co-expression networks. LPP-AS2 was found to function as a ceRNA to regulate EGFR expression by sponging miR-7-5p in glioma cells. The result of chromatin immunoprecipitation (ChIP) assays validated that c-MYC binds directly to the promoter region of LPP-AS2. As a downstream protein of EGFR, c-MYC was modulated by LPP-AS2 and in turn enhanced LPP-AS2 expression. Thus, lncRNA LPP-AS2 promoted glioma tumorigenesis via a miR-7-5p/EGFR/PI3K/AKT/c-MYC feedback loop.Conclusions: Our study elucidated that LPP-AS2 acted as an oncogene through a novel molecular pathway in glioma and might be a potential therapeutic approach for glioma diagnosis, therapy and prognosis.

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Imbalance of the reciprocally inhibitory loop between the ubiquitin-specific protease USP43 and EGFR/PI3K/AKT drives breast carcinogenesis

Cited by 73 publications

References 56 publications

Global crotonylome reveals CDYL-regulated RPA1 crotonylation in homologous recombination–mediated DNA repair

Global crotonylome reveals CDYL-regulated RPA1 crotonylation in homologous recombination–mediated DNA repair

Identification of prognostic biomarkers for breast cancer based on miRNA and mRNA co‐expression network

Long noncoding RNA LPP-AS2 promotes glioma tumorigenesis via miR-7-5p/EGFR/PI3K/AKT/c-MYC feedback loop

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