scholarly journals In silico study for decoding the correlated role of MCM7 gene in progression of breast cancer and Alzheimers disorder

2021 ◽  
Author(s):  
Navneeth Sriram ◽  
Sunny Mukherjee ◽  
Mahesh Kumar Sah

Breast cancer and Alzheimers disease (AD) are two of the progressive and detrimental disorders affecting large population around the globe. While the chemotherapy of breast cancer is well established and enriched, the AD still lacks it due to unrecognized peripheral biomarkers for detection and targeted therapy. This study aimed to identify common molecular signature markers in breast cancer (grade 1, 2, and 3) and AD for the diagnosis and prognosis. We used two microarray datasets (GSE42568, GSE33000) respectively for both disorders that led to identification of two common differentially expressed genes (DEGs), namely MCM7 and CD209, as common players in both these two conditions. While the pattern of expression of CD209 gene running upregulated in both disorders, the MCM7 showed unusual contrary in its pattern of expression. The expression of MCM7 is downregulated in breast cancer but upregulated in AD. Gene set and protein overrepresentation analysis, protein-protein interaction (PPI), and protein subcellular localization analyses of this underrated MCM7 gene was performed with further prediction and validation of its structure. The findings may pave the way in designing therapeutic approaches to ameliorate AD.

2020 ◽  
Author(s):  
Jingyang Zhou ◽  
Feng Xin ◽  
Chuyu Xiao ◽  
Wuyuan Zhou

Abstract Background: In western countries and China, back and neck pain has become a common problem that bothers daily life and severely influences the quality of our daily life. Among all factors that lead to chronic neck and back pain, IDD is the one that couldn’t be easily neglected. Methods: This study aims to figure out the critical genes and pathways involved in the development of IDD and provide a new aspect of following investigations on the etiology of IDD. We firstly systemically searched the GEO database and identified the differentially expressed genes (DEGs) from the expression profile dataset we selected. We secondly constructed the protein-protein interaction (PPI) network for DEGs, identified the top ten hub genes from the whole PPI network and found two statically and medically significant modules from the network, we then performed the GO and KEGG analysis on the DEGs, top ten hub genes, the PPI network and the two statically and medically modules. In the end, we provided the primers of the mRNAs of all DEGs, which will be useful for the validation experiment of this study. Results: FN1, MMP2, POSTN, COL3A1, TIMP3, FBN1, GJA1, TGFBI, EFEMP1 and ID1 were top ten hub genes identified from this study, and they may play a vital role in the development of IDD. Angiogenesis and integrin binging are crucial biological process and molecular function defined in this study, which are worthy of being intensely investigated.Conclusion: More studies on the top ten hub genes, the role of angiogenesis and integrin binding in IDD are urgently needed, which will benefit the prevention, screening, diagnosis and prognosis of IDD.


2021 ◽  
Author(s):  
Binayak Kumar ◽  
Peeyush Prasad ◽  
Ragini Singh ◽  
Ram Krishana Sahu ◽  
Ashutosh Singh ◽  
...  

Abstract CDK4/6 inhibitors (Abemaciclib, Ab and Palbociclib, Pb) stop the G1-phase in cell-cycle being used to cure advanced stage of breast cancer (BC). Acquired resistance is a major challenge in BC therapy. The molecular signature of the therapy resistance for Ab and Pb drugs in BC should be explored. Here, we developed Ab/Pb-resistant cell-models and explored the molecular changes. Drug’s resistance cells were developed in MCF-7 cells by continuous drug treatment and it was confirmed by MTT-assay, PI-staining-microscopy, and real-time-qPCR. Global proteome profiling done by Labelled-free-Proteome-Orbitrap-Fusion-MS-MS technique. Bioinformatics tools used to analyse the proteome data. Ab-resistant and Pb-resistant MCF-7 cells showed increased tolerance for the respective drug. The BCL-2 and MCL-1 survival genes were up-regulated, while the apoptosis genes BAD, BAX, CASP-3 and PARP-1were down-regulated in the resistant cells. Expression of the MDR-1, ABCG2, ESR-1, CDK4, CDK6, and Cyclin-D1 genes were increased in both resistance cells. For proteomics, 237 and 239 proteins were expressed differently in the resistant Ab and Pb cells, respectively. The NUDT5, PEPD, ABAT, ATP1B1, GGCT, and SELENBP1 proteins were down-regulated and the SBSN, HSD17B10, CD9, PDIA3, PSMB4, SLC2A1, and VTN proteins were up-regulated in Ab-resistant cells. The NUDT5, PEPD, and GGCT proteins were down-regulated, while CD47, HIST1H2BN, LMNA, VTN, PSMB5, HBB, PSMA7, FLNB, PRDX4, VDAC1, GOT2, HSPA5, SERPINH1, EIF4A2, FTH, and VIM proteins were up-regulated in Pb-resistant cells. These proteins are a new set of prognostic markers and drug targets for overcoming the respective drug resistance. However, it is necessary to perform an in vivo or clinical assessment.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sepideh Dashti ◽  
Mohammad Taheri ◽  
Soudeh Ghafouri-Fard

Abstract Breast cancer is a highly heterogeneous disorder characterized by dysregulation of expression of numerous genes and cascades. In the current study, we aim to use a system biology strategy to identify key genes and signaling pathways in breast cancer. We have retrieved data of two microarray datasets (GSE65194 and GSE45827) from the NCBI Gene Expression Omnibus database. R package was used for identification of differentially expressed genes (DEGs), assessment of gene ontology and pathway enrichment evaluation. The DEGs were integrated to construct a protein–protein interaction network. Next, hub genes were recognized using the Cytoscape software and lncRNA–mRNA co-expression analysis was performed to evaluate the potential roles of lncRNAs. Finally, the clinical importance of the obtained genes was assessed using Kaplan–Meier survival analysis. In the present study, 887 DEGs including 730 upregulated and 157 downregulated DEGs were detected between breast cancer and normal samples. By combining the results of functional analysis, MCODE, CytoNCA and CytoHubba 2 hub genes including MAD2L1 and CCNB1 were selected. We also identified 12 lncRNAs with significant correlation with MAD2L1 and CCNB1 genes. According to The Kaplan–Meier plotter database MAD2L1, CCNA2, RAD51-AS1 and LINC01089 have the most prediction potential among all candidate hub genes. Our study offers a framework for recognition of mRNA–lncRNA network in breast cancer and detection of important pathways that could be used as therapeutic targets in this kind of cancer.


Author(s):  
Khulood M. Al-Khater ◽  
Sarah Almofty ◽  
Vijaya Ravinayagam ◽  
Noor Alrushaid ◽  
Suriya Rehman

Author(s):  
Aurelia Spinei ◽  
◽  
Anca Chiriac ◽  
Iurie Spinei ◽  
Gheorghe Tibirna ◽  
...  

Despite advancement in tumors treatment, oral cancer has a poor prognosis and is often detected at late stage. Recent advancement in metagenomic technologies may be useful in identifying oral tumors–related microbiome, their genomes, virulence properties, and their interaction with host immunity. Alteration in the oral commensal microbial communities have potential application as a diagnostic tool to predict oral tumors. To develop highly precise and effective therapeutic approaches, identification of specific oral microbiomes may be required. In this review, we narrate the role of microbiome in the progression of oral tumors and its role as an early diagnostic and prognostic biomarker for oral tumors.


Endocrinology ◽  
2021 ◽  
Author(s):  
Katrina M Piemonte ◽  
Lindsey J Anstine ◽  
Ruth A Keri

Abstract Chromosomal instability (CIN), or the dynamic change in chromosome number and composition, has been observed in cancer for decades. Recently, this phenomenon has been implicated as facilitating the acquisition of cancer hallmarks and enabling the formation of aggressive disease. Hence, CIN has the potential to serve as a therapeutic target for a wide range of cancers. CIN in cancer often occurs as a result of disrupting key regulators of mitotic fidelity and faithful chromosome segregation. As a consequence of their essential roles in mitosis, dysfunctional centrosomes can induce and maintain CIN. Centrosome defects are common in breast cancer, a heterogeneous disease characterized by high CIN. These defects include amplification, structural defects, and loss of primary cilium nucleation. Recent studies have begun to illuminate the ability of centrosome aberrations to instigate genomic flux in breast cancer cells and the tumor evolution associated with aggressive disease and poor patient outcomes. Here, we review the role of CIN in breast cancer, the processes by which centrosome defects contribute to CIN in this disease, and the emerging therapeutic approaches that are being developed to capitalize upon such aberrations.


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