Deglycosylated Azithromycin Targets Transgelin to Enhance Intestinal Smooth Muscle Function

Zhong, Weilong; Sun, Bo; Ruan, Hao; Yang, Guang; Bian, Qian; Cao, Hailong; He, Lingfei; Fan, Yong; Roberts, Arthur G.; Liu, Xiang; Hu, Xuejiao; Yuan, Liang; Ye, Qing; Wang, Bangmao; Yang, Cheng; Sun, Tao; Zhou, Honggang

doi:10.1016/j.isci.2020.101464

Cited by 8 publications

(5 citation statements)

References 42 publications

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“…Previous studies found that PLK1-targeted siRNA could effectively inhibit the proliferation of various malignant tumors, block tumor cells at the G2/M stage, and induce tumor cell apoptosis and sensitivity to radiotherapy and chemotherapy (40)(41)(42). Therefore, the development of PLK1 inhibitors as therapeutic targets may provide novel ideas regarding an individualized treatment for basal-cell type breast cancer (43)(44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of key genes in triple negative breast cancer and validation of oncogene PLK1

Ren¹,

Deng²,

Zhang³

et al. 2020

Ann Transl Med

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Background: Breast cancer is the most common malignancy in women. Triple-negative breast cancer (TNBC) refers to a special subtype that is deficient in the expression of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER-2). In this study, a variety of bioinformatics analysis tools were used to screen Hub genes related to the occurrence and development of triple negative breast cancer, and their biological functions were analyzed.Methods: Gene Expression Omnibus (GEO) breast cancer microarray data GSE62931 was selected as the research object. The differentially expressed genes (DEGs) were screened and the protein-protein interaction (PPI) network of DEGs was constructed using bioinformatics tools. The Hub genes were also screened. The Gene Ontology (GO) knowledgebase and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for biological enrichment analysis. The Gene Expression Profiling Interactive Analysis (GEPIA) online tool was used to verify the expression of the screened genes and patient survival. The effects of polo-like kinase 1 (PLK1) on the proliferation, invasion, migration, and dryness of breast cancer cells were verified using cell counting kit 8 (CCK-8), transwell migration assays, scratch tests, and clone formation tests. An animal model of subcutaneous xenotransplantation of breast cancer was established to evaluate the effect of PLK1 on the proliferation of breast cancer.Results: A total of 824 DEGs were screened by GSE62931 microarray data; 405 of which were upregulated and 419 of which were down-regulated. Functional enrichment analysis showed that these DEGs were mainly enriched in cancer-related pathways and were primarily involved in biological processes (BP) such as cell and mitotic division. From the Hub gene screening, PLK1 was further identified as the Hub gene associated with TNBC. Cell and animal experiments indicated that PLK1 promotes the proliferation, invasion, migration, and clone formation of breast cancer cells.Conclusions: Gene chip combined with bioinformatics methods can effectively analyze the DEGs related to the occurrence and development of breast cancer, and the screening of PLK1 can provide theoretical guidance for further research on the molecular mechanism of breast cancer and the screening of molecular markers.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of key genes in triple negative breast cancer and validation of oncogene PLK1

Ren¹,

Deng²,

Zhang³

et al. 2020

Ann Transl Med

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“…The mice were treated with atropine (15 mg kg −1 ) (CAS 51-55-8, NARUREWILL, China) and sucralfate (5 mg kg −1 ) (CAS 54182-58-0, DEMO Medical Technology, China) twice daily by gavage for 2 days. 33 Then, the mice were treated with 200 μL antibiotic cocktail (ampicillin 1 g L −1 , metronidazole 1 g L −1 , vancomycin 0.5 g L −1 , and neomycin 0.5 g L −1 ) (Sigma, USA) once a day for 3 days. Afterwards, the mice were randomized into 3 groups: the model group, FMT-MRS group and FMT-LGGs group.…”

Section: Methodsmentioning

confidence: 99%

Lactobacillus rhamnosus GG supernatant promotes intestinal mucin production through regulating 5-HT4R and gut microbiota

Qin

Zhou

et al. 2022

Food Funct.

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“…We proposed a strategy to enhance the stability of ZEB1 by inhibiting the interaction between TAGLN and USP1 and reducing the retention of USP1 in the cytoplasm. According to previous studies, some macrocyclic monomers have excellent binding activity to TAGLN [ 18 ]. Therefore, we randomly selected 200 plant-derived extracts with macrocyclic monomer and screened for inhibitors of the TAGLN/USP1 interactive interface by virtual docking.…”

Section: Resultsmentioning

confidence: 99%

Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging

Huang

Jin³

et al. 2023

Cell Biosci

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Background Ultraviolet A (UVA) irradiation can lead to skin damage and premature skin aging known as photoaging. This work found that UVA irradiation caused an imbalance between dermal matrix synthesis and degradation through the aberrant upregulation of transgelin (TAGLN) and studied the underlying molecular mechanism. Results Co-immunoprecipitation and proximal ligation assay results showed that TAGLN can interact with USP1. USP1 can be retained in the cytoplasm by TAGLN in UVA-induced cells, which inhibits the interaction between USP1/zinc finger E-box binding homeobox 1 (ZEB1), promote the ubiquitination degradation of ZEB1, and lead to photoaging. TAGLN knockdown can release USP1 retention and help human skin fibroblasts (HSFs) resist UVA-induced damage. The interactive interface inhibitors of TAGLN/USP1 were screened via virtual docking to search for small molecules that inhibit photoaging. Zerumbone (Zer), a natural product isolated from Zingiber zerumbet (L.) Smith, was screened out. Zer can competitively bind TAGLN to reduce the retention of USP1 in the cytoplasm and the degradation of ZEB1 ubiquitination in UV-induced HSFs. The poor solubility and permeability of Zer can be improved by preparing it as a nanoemulsion, which can effectively prevent skin photoaging caused by UVA in wild-type (WT) mice. Zer cannot effectively resist the photoaging caused by UVA in Tagln−/− mice because of target loss. Conclusions The present results showed that the interaction of TAGLN and USP1 can promote ZEB1 ubiquitination degradation in UV-induced skin photoaging, and Zer can be used as an interactive interface inhibitor of TAGLN/USP1 to prevent photoaging.

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Deglycosylated Azithromycin Targets Transgelin to Enhance Intestinal Smooth Muscle Function

Cited by 8 publications

References 42 publications

Bioinformatics analysis of key genes in triple negative breast cancer and validation of oncogene PLK1

Bioinformatics analysis of key genes in triple negative breast cancer and validation of oncogene PLK1

Lactobacillus rhamnosus GG supernatant promotes intestinal mucin production through regulating 5-HT4R and gut microbiota

Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging

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