scholarly journals Discovery of a Robust Gene Regulatory Network with a Complex Transcription Factor Network on Organ Cancer Cell-line RNA Sequence Data

2019 ◽  
Vol 19 (0) ◽  
pp. 32-55
Author(s):  
Bharata Kalbuaji ◽  
Y-H. Taguchi ◽  
Akihiko Konagaya
Keyword(s):  
Transcription Factor ◽  
Cell Line ◽  
Gene Regulatory Network ◽  
Cancer Cell ◽  
Regulatory Network ◽  
Sequence Data ◽  
Cancer Cell Line ◽  
Rna Sequence ◽  
Transcription Factor Network ◽  
Gene Regulatory

Deciphering the transcription factor-microRNA-target gene regulatory network associated with graphene oxide cytotoxicity

2018 ◽  
Vol 12 (9) ◽  
pp. 1014-1026 ◽  
Author(s):  
Masoumeh Farahani ◽  
Mostafa Rezaei–Tavirani ◽  
Hakimeh Zali ◽  
Afsaneh Arefi Oskouie ◽  
Meisam Omidi ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Graphene Oxide ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Target Gene ◽  
Microrna Target ◽  
Gene Regulatory

scholarly journals Transcription factor c-jun regulates β3Gn-T8 expression in gastric cancer cell line SGC-7901

2016 ◽  
Vol 36 (3) ◽  
pp. 1353-1360 ◽  
Author(s):  
Zhi Jiang ◽  
Zhenhua Liu ◽  
Shitao Zou ◽  
Jianlong Ni ◽  
Li Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Cell Line ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Factor C

scholarly journals Regulatory landscapes of specific miRNAs are conserved between cell lines and primary tumors

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 633
Author(s):  
Hanwen Zhu ◽  
Boting Ning
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Mirna Expression ◽  
Regulatory Network ◽  
Human Cancer ◽  
Cancer Cell Line ◽  
Cancer Type ◽  
Cancer Tissues

Background: MicroRNAs are essential gene expression regulators and play important roles in various biological processes, such as cancer. They have shown great translational promise as either diagnostic biomarkers or therapeutic targets. While the similarities between transcriptomic profiles from The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia have been thoroughly studied before, less is known on the microRNA side. This project aims to provide critical biological knowledge on the extent of consensus microRNA expression and regulation between cell line models and primary human tumors.  Method: First, we examined the similarity of miRNA expression profiles between CCLE cell lines and TCGA tumor samples for each cancer type. Next, we compared the expression of miRNAs associating the hallmarks of cancer pathways. Finally, we constructed miRNA-mRNA regulatory network for each cancer type and evaluated whether the regulatory role of each miRNA is conserved between cell lines and tumor samples.   Results: Our results indicate that, similar to gene expression, how well cancer cell line microRNA expression would capture the transcriptomic profile of human cancer tissues is greatly affected by the tumor type and purity. The cell-type composition for a cancer type also affects how accurately cancer cell lines could reflect the miRNA expression in tumor tissues. Furthermore, through network analysis, we show that certain microRNAs, not all, regulate the same set of target genes in both the cell line and human cancer tissues.  Conclusions: Through systematically comparing the miRNA expression profile and the regulatory network, our study highlights the biological differences between cell line and tumor samples and provides resources for future miRNA and cancer studies.

scholarly journals A Knowledge-guided Mechanistic Model of Synthetic Lethality in the HCT116 Vorinostat-resistant Colon Cancer Xenograft Model Cell-line

2021 ◽  
Author(s):  
Paul Aiyetan
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Regulatory Network ◽  
Synthetic Lethality ◽  
Xenograft Model ◽  
Cancer Cell Line ◽  
Regulatory Pathways ◽  
Model Cell

With an overall lifetime risk of about 4.3% and 4.0%, in men and women respectively, colorectal cancer remains the third leading cause of cancer-related deaths in the United States. In persons aged 55 and below, its rate increased at 1% per year in the years 2008 to 2017 despite the steady decline associated with improved screening, early diagnosis and treatment in the general population. Besides standardized therapeutic regimen, many trials continue to evaluate the potential benefits of vorinostat, mostly in combination with other anti-neoplastic agents for its treatment. Vorinostat, an FDA approved anti-cancer drug known as suberoylanilide hydroxamic acid (SAHA), an histone deacylase (HDAC) inhibitor, through many mechanisms, causes cancer cell arrest and death. However, like many other anti-neoplastic agents, resistance and or failures have been observed. In the HCT116 colon cancer cell line xenograft model, exploiting potential lethal molecular interactions by additional gene knockouts restored vorinotat sensitivity. This phenomenon, known as synthetic lethality, offers a promise to selectively target cancer cells. Although without clearly delineated understanding of underlying molecular processes, it has been demonstrated as an effective cancer-killing mechanism. In this study, we aimed to elucidate mechanistic interactions in multiple perturbations of identified synthetically lethal experiments, particularly in the vorinostat-resistant HCT116 (colon cancer xenograft model) cell line. Given that previous studies showed that knocking down GLI1, a downstream transcription factor involved in the Sonic Hedgehog pathway -- an embryonal gene regulatory process, resulted in restoration of vorinostat sensitivity in the HCT116 colorectal cancer cell line, we hypothesized that vorinostat resistance is a result of upregulation of embryonal cellular differentiation processes; we hypothesized that elucidated regulatory mechanism would include crosstalks that regulate this biological process. We employed a knowledege-guided fuzzy logic regulatory inference method to elucidate mechanistic relationships. We validated inferred regulatory models in independent datasets. In addition, we evaluated the biomedical significance of key regulatory network genes in an independent clinically annotated dataset. We found no significant evidence that vorinostat resistance is due to an upregulation of embryonal gene regulatory pathways. Our observation rather support a topological rewiring of canonical oncogenic pathways around the PIK3CS, AKT, RAS/BRAF etc. regulatory pathways. Reasoning that significant regulatory network genes are likely implicated in the clinical course of colorectal cancer, we show that the identified key regulatory network genes' expression profile are able to predict short- to medium-term survival in colorectal cancer patients -- providing a rationale basis for prognostification and potentially effective combination of therapeutics that target these genes along with vorinostat in the treatment of colorectal cancer.

scholarly journals Tfap2a is a novel gatekeeper of differentiation in renal progenitors during kidney development

2018 ◽  
Author(s):  
Brooke E. Chambers ◽  
Gary F. Gerlach ◽  
Karen H. Chen ◽  
Eleanor G. Clark ◽  
Ignaty Leshchiner ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Genetic Control ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Kidney Development ◽  
Distal Segment ◽  
Distal Nephron ◽  
Nephron Segment ◽  
Gene Regulatory ◽  
First Time

AbstractRenal functional units known as nephrons undergo patterning events during development that create a segmental array of cellular populations with discrete physiological tasks. Knowledge about the terminal differentiation programs of each nephron segment has central importance for understanding kidney disease and to advance regenerative medicine, as mammalian nephrons grown in organoid cultures from pluripotent cells fail to terminally differentiate. Here, from a novel forward genetic screen using zebrafish we report the discovery that transcription factor AP-2 alpha (tfap2a) coordinates a gene regulatory network that controls the progression of nephron distal segment progenitors into the differentiated state. Overexpression of tfap2a rescued differentiation in mutants and caused ectopic expression of distal segment markers in wild-type nephrons, indicating tfap2a is sufficient to instigate the distal segment differentiation program. tfap2a/2b deficiency exacerbated distal nephron segment differentiation defects, revealing functional redundancy where tfap2a has a dominant role upstream of its family member. With further genetic studies, we assembled a blueprint of the tfap2a gene regulatory network during nephrogenesis. We demonstrate that tfap2a acts downstream of Iroquois homeobox 3b, a conserved distal lineage transcription factor. tfap2a controls a circuit consisting of irx1a, tfap2b, and genes encoding solute transporters that dictate the specialized metabolic functions of the distal nephron segments, and we show for the first time that this regulatory node is distinct from the pathway circuits controlling aspects such as apical-basal polarity and ciliogenesis during the differentiation process. Thus, our studies reveal new insights into the genetic control of differentiation, where tfap2a regulates the suite of segment transporter traits. These findings have relevance for understanding renal birth defects, as well as efforts to recapitulate nephrogenesis in vivo to make functional units that can facilitate organoid applications such as drug discovery and regenerative therapies.Summary StatementHere, we report for the first time that transcription factor AP-2 alpha (tfap2a) controls the progression from nephron progenitor into the fully differentiated state. This fundamentally deepens our knowledge about the genetic control of kidney development.

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