Impaired expression of Drosha in breast cancer

Zonouzi, Ali Akbar Poursadegh; Shekari, Mohammad; Nejatizadeh, Azim; Shakerizadeh, Samira; Fardmanesh, Hedieh; Zonouzi, Ahmad Poursadegh; Rahmati-Yamchi, Mohammad; Tozihi, Majid

doi:10.3233/bd-170274

Cited by 9 publications

(2 citation statements)

References 39 publications

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“…HSPA5 [87], F2RL1 [58], AR (androgen receptor) [100], SOCS1 [63], RUNX2 [542] and ESR1 [543] were an important participant in obesity. HSPA5 [293], AR (androgen receptor) [309], TCF4 [320], SOCS1 [255], PTN (pleiotrophin) [251], hsa-mir-21-3p [544], SOX2 [545], GATA2 [546], RUNX2 [547], DROSHA [548], ESR1 [549] and PAX3 [550] have been discovered to be involved in the cancer. HSPA5 [376], RIN3 [350], PTN (pleiotrophin) [339], DISC1 [398], hsa-mir-378a-5p [551], hsa-mir-5010-3p [552] and hsa-mir-21-3p [553] are believed to be associated with neurological and psychological problems.…”

Section: Discussionmentioning

confidence: 99%

The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

Vastrad¹,

Vastrad²

2023

Preprint

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Polycystic ovary syndrome (PCOS) is is associated with infertility, obesity, insulin resistance, hyperinsulinemia, type 2 diabetes mellitus, hypertension, cardiovascular problems, neurological and psychological problems and cancer. The specific mechanism of PCOS and its complications remains unclear. The aim of this study was to apply a bioinformatics approach to reveal related pathways or genes involved in the development of PCOS and its complications. The next generation squancing (NGS) datset GSE199225 was downloaded from the gene expression omnibus (GEO) database. Differentially expressed gene (DEG) analysis was performed using DESeq2. The g:Profiler was utilized to analyze the functional enrichment, gene ontology (GO) and REACTOME pathway of the differentially expressed genes. A protein-protein interaction (PPI) network was constructed and module analysis was performed using HiPPIE and cytoscape. The miRNA-hub gene regulatory network and TF-hub gene regulatory network were also constructed for research. The expression of the hub genes was validated using receiver operating characteristic (ROC) curve analysis. We have identified 957 DEGs in total, including 478 up regulated genes and 479 down regulated gene. GO and REACTOME illustrated that DEGs in PCOS were significantly enriched in regulation of molecular function, developmental process, interferon signaling and platelet activation, signaling and aggregation. Finally, through analyzing the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network, we screened hub genes HSPA5, PLK1, RIN3, DBN1, CCDC85B, DISC1, AR, MTUS2, LYN and TCF4 by the Cytoscape software. This study uses a series of bioinformatics technologies to obtain hug genes and key pathways related to PCOS and its complications. These analysis results provide us with novel ideas for finding biomarkers and treatment methods for PCOS and its complications.

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Section: Discussionmentioning

confidence: 99%

The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

Vastrad¹,

Vastrad²

2023

Preprint

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“…Moreover, expression of DROSHA has been recently shown to be impaired in breast cancer patients, although the molecular mechanisms by which this may be relevant for cancer development remain to be defined (Poursadegh Zonouzi et al, 2017). …”

Section: Discussionmentioning

confidence: 99%

DROSHA associates to DNA damage sites and is required for DNA repair

Cabrini

Roncador

Galbiati

et al. 2018

Preprint

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The DNA damage response (DDR) is the signaling cascade through which a cell recognizes DNA lesions, and promotes their resolution via the repair pathways of Non-Homologous End Joining (NHEJ), or Homologous Recombination (HR). We recently demonstrated that DROSHA boosts DDR signaling by processing damage-induced long non-coding RNAs into smaller DNA damage response RNAs (DDRNAs). However, the location at which DROSHA exerts its DDR functions, relative to sites of DNA damage, remains unknown.To investigate DROSHA's localization during DDR activation, we used the DiVA cellular system, which allows the controlled induction of several DNA double strand breaks (DSBs) in the human genome. Indeed, by genome wide chromatin immunoprecipitation followed by next generation sequencing, we demonstrate that DROSHA associates with DSBs. In support of this, DSB-recruitment of DROSHA is detectable at the single-cell level by Proximity Ligation Assay between DROSHA and known DDR markers, and by DNA damage in situ ligation followed by Proximity Ligation Assay (DI-PLA), which demonstrates proximity of DROSHA to DNA ends. DROSHA recruitment occurs at both genic and inter-genic DSBs, suggesting that its recruitment is independent from ongoing transcription preceding damage generation. DROSHA's recruitment to DNA lesions occurs throughout the cell cycle, and with a preference for NHEJ-prone DSBs. Consistently, inhibition of the HR pathway increases DROSHA recruitment, and DROSHA knock down strongly impairs NHEJ efficiency in a GFP-reporter cellular system for monitoring NHEJ DNA repair. Overall, these results demonstrate that DROSHA acts locally at sites of DNA damage to promote NHEJ DNA repair.

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