Identification of lymph node metastasis-related microRNAs in breast cancer using bioinformatics analysis

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Abstract

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Abstract

Background:

Lymph node metastasis is a significant problem in breast cancer, and its underlying molecular mechanism is still unclear. The purpose of this study is to research the molecular mechanism and to explore the key RNAs and pathways that mediate lymph node metastasis in breast cancer.

Methods:

GSE100453 and GSE38167 were downloaded from the Gene Expression Omnibus (GEO) database and 569 breast cancer statistics were also downloaded from the TCGA database. Differentially expressed miRNAs were calculated by using R software and GEO2R. Gene ontology and Enriched pathway analysis of target mRNAs were analyzed by using the Database for Database of Annotation Visualization and Integrated Discovery (DAVID) and R software. The protein–protein interaction (PPI) network was performed according to Metascape, String, and Cytoscape software.

Results:

In total, 6 differentially expressed miRNAs were selected, and 499 mRNAs were identified after filtering. The research of the Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated that mRNAs enriched in certain tumor pathways. Also, certain hub mRNAs were highlighted after constructed and analyzed the PPI network. A total of 3 out of 6 miRNAs had a significant relationship with the overall survival ( P < .05) and showed a good ability of risk prediction model of over survival.

Conclusions:

By utilizing bioinformatics analyses, differently expressed miRNAs were identified and constructed a complete gene network. Several potential mechanisms and therapeutic and prognostic targets of lymph node metastasis were also demonstrated in breast cancer.

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Most cited references 29

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Identification of Potential Key Genes and Pathways in Early-Onset Colorectal Cancer Through Bioinformatics Analysis

Bin Zhao, Zulqarnain Baloch, Yunhan Ma … (2019)

This study was designed to identify the potential key protein interaction networks, genes, and correlated pathways in early-onset colorectal cancer (CRC) via bioinformatics methods. We selected microarray data GSE4107 consisting 12 patient’s colonic mucosa and 10 healthy control mucosa; initially, the GSE4107 were downloaded and analyzed using limma package to identify differentially expressed genes (DEGs). A total of 131 DEGs consisting of 108 upregulated genes and 23 downregulated genes of patients in early-onset CRC were selected by the criteria of adjusted P values <.01 and |log2 fold change (FC)| ≥ 2. The gene ontology functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were accomplished to view the biological process, cellular components, molecular function, and the KEGG pathways of DEGs. Finally, protein–protein interactions (PPIs) were constructed, and the hub protein module was identified. Genes such as ACTA2, ACTG2, MYH11, CALD1, MYL9, TPM2, and LMOD1 were strongly implicated in CRC. In summary, in this study, we indicated that molecular mechanisms were involved in muscle contraction and vascular smooth muscle contraction signaling pathway, which improve our understanding of CRC and could be used as new therapeutic targets for CRC.

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Anti-glucocorticoid-induced Tumor Necrosis Factor–Related Protein (GITR) Therapy Overcomes Radiation-Induced Treg Immunosuppression and Drives Abscopal Effects

Jonathan E Schoenhals, Taylor Cushman, Hampartsoum Barsoumian … (2018)

Despite the potential to cure metastatic disease, immunotherapy on its own often fails outright or early on due to tumor immune evasion. To address this obstacle, we investigated combinations of anti-GITR, anti-PD1 and radiation therapy (XRT) in our previously developed anti-PD1 resistant 344SQ non-small cell lung adenocarcinoma preclinical tumor model. We hypothesized that targeting multiple mechanisms of immune evasion with this triple therapy would lead to an enhanced tumor-specific immune response and improve survival more so than any mono- or dual therapy. In a two tumor 344SQR murine model, treatment with anti-GITR, anti-PD1, and XRT led to significantly improved survival and an abscopal response, with half of the mice becoming tumor free. These mice showed durable response and increased CD4+ and CD8+ effector memory on tumor rechallenge. Regulatory T cells (Tregs) expressed the highest level of GITR at the tumor site and anti-GITR therapy drastically diminished Tregs at the tumor site. Anti-tumor effects were largely dependent on CD4+ T cells and partially dependent on CD8+ T cells. Anti-GITR IgG2a demonstrated superior efficacy to anti-GITR IgG1 in driving antitumor effects. Collectively, these results suggest that combinatorial strategies targeting multiple points of tumor immune evasion may lead to a robust and lasting antitumor response.

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The disordered N-terminus of HDAC6 is a microtubule-binding domain critical for efficient tubulin deacetylation.

Kseniya Ustinova, Zora Nováková, Makoto Saito … (2020)

Histone deacetylase 6 (HDAC6) is a multidomain cytosolic enzyme having tubulin deacetylase activity that has been unequivocally assigned to the second of the tandem catalytic domains. However, virtually no information exists on the contribution of other HDAC6 domains on tubulin recognition. Here, using recombinant protein expression, site-directed mutagenesis, fluorimetric and biochemical assays, microscale thermophoresis, and total internal reflection fluorescence microscopy, we identified the N-terminal, disordered region of HDAC6 as a microtubule-binding domain and functionally characterized it to the single-molecule level. We show that the microtubule-binding motif spans two positively charged patches comprising residues Lys-32 to Lys-58. We found that HDAC6-microtubule interactions are entirely independent of the catalytic domains and are mediated by ionic interactions with the negatively charged microtubule surface. Importantly, a crosstalk between the microtubule-binding domain and the deacetylase domain was critical for recognition and efficient deacetylation of free tubulin dimers both in vitro and in vivo Overall, our results reveal that recognition of substrates by HDAC6 is more complex than previously appreciated and that domains outside the tandem catalytic core are essential for proficient substrate deacetylation.

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Author and article information

Journal

Journal ID (nlm-ta): Medicine (Baltimore)

Journal ID (iso-abbrev): Medicine (Baltimore)

Journal ID (publisher-id): MEDI

Title: Medicine

Publisher: Lippincott Williams & Wilkins (Hagerstown, MD )

ISSN (Print): 0025-7974

ISSN (Electronic): 1536-5964

Publication date Collection: 25 September 2020

Publication date (Electronic): 25 September 2020

Volume: 99

Issue: 39

Electronic Location Identifier: e22105

Affiliations

Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China.

Author notes

[∗ ]Correspondence: Liqin Shen, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou 215004, Jiangsu, PR China (e-mail: 737443291@ 123456qq.com ).

Article

Publisher ID: MD-D-20-01541 Accession ID: 22105

DOI: 10.1097/MD.0000000000022105

PMC ID: 7523764

PubMed ID: 32991406

SO-VID: f3f9654b-db87-460b-95a1-68a34cfadeee

License:

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

History

Date received : 24 February 2020

Date revision received : 17 June 2020

Date accepted : 6 August 2020

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Keywords: bioinformatics,breast cancer,lymph node metastasis,mirna-mrna network

Data availability:

Keywords: bioinformatics, breast cancer, lymph node metastasis, mirna-mrna network

Identification of lymph node metastasis-related microRNAs in breast cancer using bioinformatics analysis

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Karger: Oncology

Most cited references 29

Identification of Potential Key Genes and Pathways in Early-Onset Colorectal Cancer Through Bioinformatics Analysis

Anti-glucocorticoid-induced Tumor Necrosis Factor–Related Protein (GITR) Therapy Overcomes Radiation-Induced Treg Immunosuppression and Drives Abscopal Effects

The disordered N-terminus of HDAC6 is a microtubule-binding domain critical for efficient tubulin deacetylation.

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