TP63, SOX2, and KLF5 Establish a Core Regulatory Circuitry That Controls Epigenetic and Transcription Patterns in Esophageal Squamous Cell Carcinoma Cell Lines

Jiang, Yan‐Yi; Jiang, Yuan; Li, Chunquan; Zhang, Ying; Dakle, Pushkar; Kaur, Harvinder; Deng, Jianwen; Lin, Ruby Yu-Tong; Lin, Han; Xie, Jian‐Jun; Yan, Yongnian; Doan, Ngan; Zheng, Yueyuan; Mayakonda, Anand; Hazawa, Masaharu; Xu, Liang; Li, Yanyu; Aswad, Luay; Jeitany, Maya; Kanojia, Deepika; Guan, Xin‐Yuan; Said, Jonathan; Yang, Wei; Fullwood, Melissa J.; Lin, De–Chen; Koeffler, H. Phillip

doi:10.1053/j.gastro.2020.06.050

Cited by 105 publications

(120 citation statements)

References 70 publications

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“…HEIH was differentially expressed in EC, and participated in the occurrence and development of EC 9 , suggesting that HEIH may be a possible therapeutic target for the treatment of EC. miR-185-5p overexpression was able to inhibit the invasion and migration of ESCC cells 19 , and KLF5 was the core regulatory factor for ESCC cells 20 . Given that, we detected HEIH, miR-185, and KLK5 expression by RT-qPCR and western blot assay in cancer and non-tumoral tissues of EC patients, and found that HEIH and KLK5 were elevated, and miR-185 was declined in EC tissues vs non-tumoral tissues (Fig.…”

Section: Resultsmentioning

confidence: 95%

RETRACTED ARTICLE: Long noncoding RNA HEIH depletion depresses esophageal carcinoma cell progression by upregulating microRNA-185 and downregulating KLK5

Wang

Hao

et al. 2020

Cell Death Dis

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Numerous studies have reported the association of long non-coding RNAs (lncRNAs) in cancers, yet the function of lncRNA high expressed in hepatocellular carcinoma (HEIH) in esophageal carcinoma (EC) has seldom been explored. Here, we aimed to explore the mechanism of HEIH on EC via microRNA-185 (miR-185)/kallikrein-related peptidase 5 (KLK5) modulation. Cancer and non-tumoral tissues were collected, in which HEIH, miR-185 and KLK5 expression were detected, as well as their correlations. Also, the relation between the prognosis of EC patients and HEIH/miR-185/KLK5 expression was clarified. EC cells (KYSE-30 and TE-1) were screened for subsequent gain- and loss-of-function assays and their biological functions were further monitored. Tumor volume and weight in EC mice were also measured. Results from this study indicated that HEIH and KLK5 were elevated and miR-185 was declined in EC. The positive correlation was seen in HEIH and KLK5 expression, while the negative correlation was observed in HEIH or KLK5 and miR-185 expression. High HEIH and KLK5 indicated worse prognosis and high miR-185 suggested better prognosis of EC patients. Depleting HEIH or restoring miR-185 suppressed the malignant phenotypes of EC cells, and delayed tumor growth in EC mice. HEIH was found to bind with miR-185 to regulate KLK5 expression. Overexpressing KLK5 alone promoted EC cell progression while up-regulating miR-185 reversed such effects on EC cells. Collectively, we reveal that HEIH depletion dampens EC progression by upregulating miR-185 and downregulating KLK5, which provides novel treatments for EC.

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Section: Resultsmentioning

confidence: 95%

RETRACTED ARTICLE: Long noncoding RNA HEIH depletion depresses esophageal carcinoma cell progression by upregulating microRNA-185 and downregulating KLK5

Wang

Hao

et al. 2020

Cell Death Dis

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“…In the development of squamous cell carcinoma, TP63 plays an important role in chromatin remodeling and enhancer reprogramming and epidermal differentiation (20). In esophageal squamous cell carcinoma, Jiang et al (21) found that TP63, SOX2 and KLF5 are part of a core regulatory network that determines cellular chromatin accessibility, epigenetic modifications and gene expression patterns. ADUK, the orthologue of Drosophila Ulk3, is an autophagyinduced Atg1 independent pathway.…”

Section: Discussionmentioning

confidence: 99%

A Correlation Study of Prognostic Risk Prediction for Colorectal Cancer Based on Autophagy Signature Genes

et al. 2021

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Autophagy plays a complex role in tumors, sometimes promoting cancer cell survival and sometimes inducing apoptosis, and its role in the colorectal tumor microenvironment is controversial. The purpose of this study was to investigate the prognostic value of autophagy-related genes (ARGs) in colorectal cancer. We identified 37 differentially expressed autophagy-related genes by collecting TCGA colorectal tumor transcriptome data. A single-factor COX regression equation was used to identify 11 key prognostic genes, and a prognostic risk prediction model was constructed based on multifactor COX analysis. We classified patients into high and low risk groups according to prognostic risk parameters (p <0.001) and determined the prognostic value they possessed by survival analysis and the receiver operating characteristic (ROC) curve in the training and test sets of internal tests. In a multifactorial independent prognostic analysis, this risk value could be used as an independent prognostic indicator (HR=1.167, 95% CI=1.078-1.264, P<0.001) and was a robust predictor without any staging interference. To make it more applicable to clinical procedures, we constructed nomogram based on risk parameters and parameters of key clinical characteristics. The area under ROC curve for 3-year and 5-year survival rates were 0.735 and 0.718, respectively. These will better enable us to monitor patient prognosis, thus improve patient outcomes.

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“…Pan-PTM-specific antibodies are often applied for immunoaffinity enrichment prior to LC-MS/MS as well as Western blotting, protein microarrays, immunohistochemistry, and flow cytometry. Antibodies against specific modification sites known to play an important biological role are also available for certain modifications including phosphorylation, methylation, and acetylation [25][26][27]. Other PTMs face difficulties in site-specific antibody generation due to the size or transience of the PTM (e.g., ubiquitination); or lack sufficient evidence of site occupancy to invest in antibody generation [28].…”

Section: Analytical Techniques In Post-translational Modification Analysismentioning

confidence: 99%

Current Methods of Post-Translational Modification Analysis and Their Applications in Blood Cancers

Dunphy

Dowling

Bazou

et al. 2021

Cancers

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Post-translational modifications (PTMs) add a layer of complexity to the proteome through the addition of biochemical moieties to specific residues of proteins, altering their structure, function and/or localization. Mass spectrometry (MS)-based techniques are at the forefront of PTM analysis due to their ability to detect large numbers of modified proteins with a high level of sensitivity and specificity. The low stoichiometry of modified peptides means fractionation and enrichment techniques are often performed prior to MS to improve detection yields. Immuno-based techniques remain popular, with improvements in the quality of commercially available modification-specific antibodies facilitating the detection of modified proteins with high affinity. PTM-focused studies on blood cancers have provided information on altered cellular processes, including cell signaling, apoptosis and transcriptional regulation, that contribute to the malignant phenotype. Furthermore, the mechanism of action of many blood cancer therapies, such as kinase inhibitors, involves inhibiting or modulating protein modifications. Continued optimization of protocols and techniques for PTM analysis in blood cancer will undoubtedly lead to novel insights into mechanisms of malignant transformation, proliferation, and survival, in addition to the identification of novel biomarkers and therapeutic targets. This review discusses techniques used for PTM analysis and their applications in blood cancer research.

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TP63, SOX2, and KLF5 Establish a Core Regulatory Circuitry That Controls Epigenetic and Transcription Patterns in Esophageal Squamous Cell Carcinoma Cell Lines

Cited by 105 publications

References 70 publications

RETRACTED ARTICLE: Long noncoding RNA HEIH depletion depresses esophageal carcinoma cell progression by upregulating microRNA-185 and downregulating KLK5

RETRACTED ARTICLE: Long noncoding RNA HEIH depletion depresses esophageal carcinoma cell progression by upregulating microRNA-185 and downregulating KLK5

A Correlation Study of Prognostic Risk Prediction for Colorectal Cancer Based on Autophagy Signature Genes

Current Methods of Post-Translational Modification Analysis and Their Applications in Blood Cancers

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