An integrated study on TFs and miRNAs in colorectal cancer metastasis and evaluation of three co-regulated candidate genes as prognostic markers

Eskandari, Elaheh; Mahjoubi, Frouzandeh; Motalebzadeh, Jamshid

doi:10.1016/j.gene.2018.09.003

Cited by 24 publications

(12 citation statements)

References 62 publications

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“…NFYA is reported to be up-regulated in HCC, breast, lung and other types of cancers [36]. The value of NR5A2 as a key regulator for colorectal cancer metastasis was studied [37].…”

Section: Discussionmentioning

confidence: 99%

Transcription Factors Linked to the Molecular Signatures in the Development of HCC on a Cirrhotic Background

Motalebzadeh

Eskandari

2021

Preprint

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Mechanisms underlying the regulation of gene expression in cancer have been surveyed for decades to find novel prognostic factors and new targets for molecular targeted therapies in cancer. Because most cases of liver cancer are associated with liver cirrhosis, we aimed to analyze the gene expression signatures and the gene regulatory mechanism in hepatocellular carcinoma (HCC) on a cirrhotic background using high-throughput data analysis. In the present study, three valid array-based datasets containing HCC and liver cirrhosis samples were obtained to identify common differentially expressed genes (DEGs). Moreover, a comprehensive data analysis was conducted based on RNA-Seq data and using Kaplan-Meier curve analysis to find molecular signatures that reduce patients' overall survival rate. Furthermore, we proposed a gene regulatory network (GRN) to explore the possible regulatory mechanism of these molecular signatures by transcription factors in HCC progression from cirrhosis. Besides, we analyzed protein-protein interactions, gene ontology (GO), and pathway enrichment to elucidate the cellular and molecular function of the GRN elements in HCC. In this way, we found a list of 231 molecular signatures in HCC derived from cirrhosis. We also found the importance of TCF4, RUNX1, HINFP, KDM2B, MAF, JUN, NR5A2, NFYA, and AR as key differentially expressed transcription factors (DETFs) in the progression of HCC from cirrhosis. In conclusion, the identified molecular signatures and their transcription factors propose candidate prognostic markers and possible molecular targets in the progression of HCC.

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“…NFYA is reported to be up-regulated in HCC, breast, lung and other types of cancers [36]. The value of NR5A2 as a key regulator for colorectal cancer metastasis was studied [37].…”

Section: Discussionmentioning

confidence: 99%

Transcription Factors Linked to the Molecular Signatures in the Development of HCC on a Cirrhotic Background

Motalebzadeh

Eskandari

2021

Preprint

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“…In addition, ETV4 is notably related to the depth of invasion, metastasis, and recurrence of CRC, 43 , 44 , 47 and, correspondingly, patients with ETV4-positive CRC possess worse overall survival (OS) and disease-free survival (DFS) in comparison with those with ETV4-negative cancers, 44 demonstrating that ETV4 functions as a tumor-promoting factor in CRC and predicts poor survival.…”

Section: Gastrointestinal Cancersmentioning

confidence: 99%

E26 transformation-specific variant 4 as a tumor promotor in human cancers through specific molecular mechanisms

Jiang

Chen

et al. 2021

Molecular Therapy - Oncolytics

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E26 transformation-specific (ETS) variant 4 (ETV4) is an important transcription factor that belongs to the ETS transcription factor family and is essential for much cellular physiology. Recent evidence has revealed that ETV4 is aberrantly expressed in many types of tumors, and its overexpression is related to poor prognosis of cancer patients. Additionally, increasing studies have identified that ETV4 promotes cancer growth, invasion, metastasis, and drug resistance. Mechanistically, the level of ETV4 is regulated by some post-translation modulations in a broad spectrum of cancers. However, little progress has been made to comprehensively summarize the critical roles of ETV4 in different human cancers. Hence, this review mainly focuses on the physiological functions of ETV4 in various human tumors. In addition, the molecular mechanisms of ETV4-mediated cancer progression were elucidated, including how ETV4 modulates its downstream signaling pathways and how ETV4 is regulated by some factors. On this basis, the present review may provide a valuable therapeutics strategy for future cancer treatment by targeting ETV4-related pathways.

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“…Data processing inequality results in a regulatory network that includes primarily direct TF/co-TF-target interactions. ARACNe has been widely applied to several normal physiological and pathological conditions, including B-cell interactome ( Basso et al, 2005 ), breast cancer ( Lim et al, 2009 ; Remo et al, 2015 ; Walsh et al, 2017 ), prostate cancer ( Aytes et al, 2014 ), colorectal cancer ( Bae et al, 2013 ; Cordero et al, 2014 ; Sanz-Pamplona et al, 2014 ; Eskandari et al, 2018 ), glioma ( Carro et al, 2010 ), T-cell acute lymphoblastic leukemia ( Palomero et al, 2006 ), and multiple myeloma ( Agnelli et al, 2011 ), among others. Software for ARACNe is freely available for download.…”

Section: Mechanism-centric Computational Approaches For Biomarker Discoverymentioning

confidence: 99%

Mechanism-Centric Approaches for Biomarker Detection and Precision Therapeutics in Cancer

Mitrofanova

2021

Front. Genet.

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Biomarker discovery is at the heart of personalized treatment planning and cancer precision therapeutics, encompassing disease classification and prognosis, prediction of treatment response, and therapeutic targeting. However, many biomarkers represent passenger rather than driver alterations, limiting their utilization as functional units for therapeutic targeting. We suggest that identification of driver biomarkers through mechanism-centric approaches, which take into account upstream and downstream regulatory mechanisms, is fundamental to the discovery of functionally meaningful markers. Here, we examine computational approaches that identify mechanism-centric biomarkers elucidated from gene co-expression networks, regulatory networks (e.g., transcriptional regulation), protein–protein interaction (PPI) networks, and molecular pathways. We discuss their objectives, advantages over gene-centric approaches, and known limitations. Future directions highlight the importance of input and model interpretability, method and data integration, and the role of recently introduced technological advantages, such as single-cell sequencing, which are central for effective biomarker discovery and time-cautious precision therapeutics.

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An integrated study on TFs and miRNAs in colorectal cancer metastasis and evaluation of three co-regulated candidate genes as prognostic markers

Cited by 24 publications

References 62 publications

Transcription Factors Linked to the Molecular Signatures in the Development of HCC on a Cirrhotic Background

Transcription Factors Linked to the Molecular Signatures in the Development of HCC on a Cirrhotic Background

E26 transformation-specific variant 4 as a tumor promotor in human cancers through specific molecular mechanisms

Mechanism-Centric Approaches for Biomarker Detection and Precision Therapeutics in Cancer

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