Mining potentially actionable kinase gene fusions in cancer cell lines with the KuNG FU database

Somaschini, Alessio; Bella, Sebastiano Di; Cusi, Carlo; Raddrizzani, Laura; Leone, Antonella; Carapezza, Giovanni; Mazza, Tommaso; Isacchi, Antonella; Bosotti, Roberta

doi:10.1038/s41597-020-00761-2

Cited by 3 publications

(1 citation statement)

References 48 publications

(94 reference statements)

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“…With the continuous maturity of high-throughput technologies such as gene microarray technology, many expression pro les of diseases have been established, such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Reasonable analysis and integration of data in the database can effectively explore the potential biological signi cance of the data, and it is already an effective tool to nd potential targets for disease diagnosis and treatment (Lever et al,2013;Somaschini et al,2020). After screening, phospholipase C delta 3 (PLCD3) was identi ed as a key differentially expressed gene in osteoarthritis, involved in the PI3K/AKT signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the regulatory role of miR-34a-5p/PLCD3 in the progression of osteoarthritis

Ying

Jiang

et al. 2023

Funct Integr Genomics

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Osteoarthritis is a heterogeneous disease with complex etiology. However, there is no effective treatment strategy at present. The purpose of this study is to explore the miRNA-mRNA regulatory network and molecular mechanism that regulate the progression of osteoarthritis. In this article, we downloaded dataset (GSE55457, GSE82107, GSE143514 and GSE55235) from Gene Expression Omnibus (GEO) to screen differentially expressed mRNAs in osteoarthritis. Then, through weighted gene co-expression network analysis (WGCNA), functional enrichment, protein-protein interaction networks (PPI), miRNA-mRNA co-expression network, ROC curve, immune in ltration analysis and qPCR, the mRNA PLCD3, which was highly expressed in osteoarthritis and had clinical predictive value, was screened. Whereafter, we found that PLCD3 directly targets miR-34a-5p through DIANA and dual luciferase experiment. And the expression of PLCD3 and miR-34a-5p were negatively correlated. In addition, CCK-8 and wound healing showed that miR-34a-5p mimic inhibited hFLS-OA cell proliferation and promoted hFLS-OA cell migration.PLCD3 overexpression showed an opposite trend. Western further found that overexpression of miR-34a-5p reduced the protein expression levels of p-PI3K and p-AKT, while overexpression of PLCD3 also showed the opposite trend. Besides, combined with the effect of PI3K/AKT pathway inhibitor BIO(IC50 = 5.95 µM), the results showed that overexpression of miR-34a-5p increased the inhibitory effect of BIO on p-PI3K and p-AKT protein expression, while overexpression of PLCD3 signi cantly reversed the inhibitory effect. In all, the miR-34a-5p/PLCD3 axis may mediate the PI3K/AKT pathway in regulating cartilage homeostasis in synovial osteoarthritis. These data indicate that miR-34a-5p/PLCD3 may be a new prognostic factor in the pathology of synovial osteoarthritis.

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Section: Introductionmentioning

confidence: 99%

Analysis of the regulatory role of miR-34a-5p/PLCD3 in the progression of osteoarthritis

Ying

Jiang

et al. 2023

Funct Integr Genomics

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ChiTaRS 8.0: the comprehensive database of chimeric transcripts and RNA-seq data with applications in liquid biopsy

DSouza,

Bik,

Giwa

et al. 2024

Nucleic Acids Research

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Gene fusions are nucleotide sequences formed due to errors in replication and transcription control. These errors, resulting from chromosomal translocation, transcriptional errors or trans-splicing, vary from cell to cell. The identification of fusions has become critical as key biomarkers for disease diagnosis and therapy in various cancers, significantly influencing modern medicine. Chimeric Transcripts and RNA-Sequencing database version 8.0 (ChiTaRS 8.0; http://biosrv.org/chitars) is a specialized repository for human chimeric transcripts, containing 47 445 curated RNA transcripts and over 100 000 chimeric sequences in humans. This updated database provides unique information on 1055 chimeric breakpoints derived from public datasets using chromosome conformation capture techniques (the Hi-C datasets). It also includes an expanded list of gene fusions that are potential drug targets, and chimeric breakpoints across 934 cell lines, positioning ChiTaRS 8.0 as a valuable resource for testing personalized cancer therapies. By utilizing text mining on a curated selection of disease-specific RNA-sequencing data from public datasets, as well as patient blood and plasma samples, we have identified novel chimeras—particularly in diseases such as oral squamous cell carcinoma and glioblastoma—now catalogued in ChiTaRS. Thus, ChiTaRS 8.0 serves as an enhanced fusion transcript repository that incorporates insights into the functional landscape of chimeras in cancers and other complex diseases, based on liquid biopsy results.

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Comprehensive analysis of GEO data reveals potential miRNA-mRNA regulation axis and analyses the role of key regulatory axis on osteoarthritis

Ying

Jiang

et al. 2022

Preprint

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Osteoarthritis is a heterogeneous disease with complex etiology. However, there is no effective treatment strategy at present. The purpose of this study is to explore the miRNA-mRNA regulatory network and molecular mechanism that regulate the progression of osteoarthritis. In this article, we downloaded dataset (GSE55457, GSE82107, GSE143514 and GSE55235) from Gene Expression Omnibus (GEO) to screen differentially expressed mRNAs in osteoarthritis. Then, through weighted gene co-expression network analysis (WGCNA), functional enrichment, protein-protein interaction networks (PPI), miRNA-mRNA co-expression network, ROC curve, immune infiltration analysis and qPCR, the mRNA PLCD3, which was highly expressed in osteoarthritis and had clinical predictive value, was screened. Whereafter, we found that PLCD3 directly targets miR-34a-5p through DIANA and dual luciferase experiment. And the expression of PLCD3 and miR-34a-5p were negatively correlated. In addition, CCK-8 and wound healing showed that miR-34a-5p mimic inhibited hFLS-OA cell proliferation and promoted hFLS-OA cell migration. PLCD3 overexpression showed an opposite trend. Western further found that overexpression of miR-34a-5p reduced the protein expression levels of p-PI3K and p-AKT, while overexpression of PLCD3 also showed the opposite trend. Besides, combined with the effect of PI3K/AKT pathway inhibitor BIO(IC50 = 5.95 µM), the results showed that overexpression of miR-34a-5p increased the inhibitory effect of BIO on p-PI3K and p-AKT protein expression, while overexpression of PLCD3 significantly reversed the inhibitory effect. In all, the miR-34a-5p/PLCD3 axis may mediate the PI3K/AKT pathway in regulating cartilage homeostasis in synovial osteoarthritis. These data indicate that miR-34a-5p/PLCD3 may be a new prognostic factor in the pathology of synovial osteoarthritis.

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Mining potentially actionable kinase gene fusions in cancer cell lines with the KuNG FU database

Cited by 3 publications

References 48 publications

Analysis of the regulatory role of miR-34a-5p/PLCD3 in the progression of osteoarthritis

Analysis of the regulatory role of miR-34a-5p/PLCD3 in the progression of osteoarthritis

ChiTaRS 8.0: the comprehensive database of chimeric transcripts and RNA-seq data with applications in liquid biopsy

Comprehensive analysis of GEO data reveals potential miRNA-mRNA regulation axis and analyses the role of key regulatory axis on osteoarthritis

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