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Article ; Online: SR Splicing Factors Promote Cancer via Multiple Regulatory Mechanisms.

Wan, Ledong / Deng, Min / Zhang, Honghe

2022 Volume 13, Issue 9

Abstract: Substantial emerging evidence supports that dysregulated RNA metabolism is associated with tumor initiation and development. Serine/Arginine-Rich proteins (SR) are a number of ultraconserved and structurally related proteins that contain a characteristic ...

Abstract	Substantial emerging evidence supports that dysregulated RNA metabolism is associated with tumor initiation and development. Serine/Arginine-Rich proteins (SR) are a number of ultraconserved and structurally related proteins that contain a characteristic RS domain rich in arginine and serine residues. SR proteins perform a critical role in spliceosome assembling and conformational transformation, contributing to precise alternative RNA splicing. Moreover, SR proteins have been reported to participate in multiple other RNA-processing-related mechanisms than RNA splicing, such as genome stability, RNA export, and translation. The dysregulation of SR proteins has been reported to contribute to tumorigenesis through multiple mechanisms. Here we reviewed the different biological roles of SR proteins and strategies for functional rectification of SR proteins that may serve as potential therapeutic approaches for cancer.
MeSH term(s)	Arginine/metabolism ; Humans ; Neoplasms/genetics ; RNA ; RNA Splicing Factors/genetics ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Serine ; Serine-Arginine Splicing Factors/genetics ; Serine-Arginine Splicing Factors/metabolism
Chemical Substances	RNA Splicing Factors ; RNA-Binding Proteins ; Serine-Arginine Splicing Factors (170974-22-8) ; Serine (452VLY9402) ; RNA (63231-63-0) ; Arginine (94ZLA3W45F)
Language	English
Publishing date	2022-09-16
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13091659
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: SR Splicing Factors Promote Cancer via Multiple Regulatory Mechanisms

Wan, Ledong / Deng, Min / Zhang, Honghe

Genes. 2022 Sept. 16, v. 13, no. 9

2022

Abstract	Substantial emerging evidence supports that dysregulated RNA metabolism is associated with tumor initiation and development. Serine/Arginine-Rich proteins (SR) are a number of ultraconserved and structurally related proteins that contain a characteristic RS domain rich in arginine and serine residues. SR proteins perform a critical role in spliceosome assembling and conformational transformation, contributing to precise alternative RNA splicing. Moreover, SR proteins have been reported to participate in multiple other RNA-processing-related mechanisms than RNA splicing, such as genome stability, RNA export, and translation. The dysregulation of SR proteins has been reported to contribute to tumorigenesis through multiple mechanisms. Here we reviewed the different biological roles of SR proteins and strategies for functional rectification of SR proteins that may serve as potential therapeutic approaches for cancer.
Keywords	RNA ; RNA transport ; arginine ; carcinogenesis ; genome ; metabolism ; neoplasms ; serine ; spliceosomes ; therapeutics
Language	English
Dates of publication	2022-0916
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13091659
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Article ; Online: Uncertainty-aware refinement framework for ovarian tumor segmentation in CECT volume.

Hu, Jiaqi / Cui, Zhiming / Zhang, Xiao / Zhang, Jiadong / Ge, Yuyan / Zhang, Honghe / Lu, Yan / Shen, Dinggang

Medical physics

2023 Volume 51, Issue 4, Page(s) 2678–2694

Abstract: Background: Ovarian cancer is a highly lethal gynecological disease. Accurate and automated segmentation of ovarian tumors in contrast-enhanced computed tomography (CECT) images is crucial in the radiotherapy treatment of ovarian cancer, enabling ... ...

Abstract	Background: Ovarian cancer is a highly lethal gynecological disease. Accurate and automated segmentation of ovarian tumors in contrast-enhanced computed tomography (CECT) images is crucial in the radiotherapy treatment of ovarian cancer, enabling radiologists to evaluate cancer progression and develop timely therapeutic plans. However, automatic ovarian tumor segmentation is challenging due to factors such as inhomogeneous background, ambiguous tumor boundaries, and imbalanced foreground-background, all of which contribute to high predictive uncertainty for a segmentation model. Purpose: To tackle these challenges, we propose an uncertainty-aware refinement framework that aims to estimate and refine regions with high predictive uncertainty for accurate ovarian tumor segmentation in CECT images. Methods: To this end, we first employ an approximate Bayesian network to detect coarse regions of interest (ROIs) of both ovarian tumors and uncertain regions. These ROIs allow a subsequent segmentation network to narrow down the search area for tumors and prioritize uncertain regions, resulting in precise segmentation of ovarian tumors. Meanwhile, the framework integrates two guidance modules that learn two implicit functions capable of mapping query features sampled according to their uncertainty to organ or boundary manifolds, guiding the segmentation network to facilitate information encoding of uncertain regions. Results: Firstly, 367 CECT images are collected from the same hospital for experiments. Dice score, Jaccard, Recall, Positive predictive value (PPV), 95% Hausdorff distance (HD95) and Average symmetric surface distance (ASSD) for the testing group of 77 cases are 86.31%, 73.93%, 83.95%, 86.03%, 15.17 mm and 2.57 mm, all of which are significantly better than that of the other state-of-the-art models. And results of visual comparison shows that the compared methods have more mis-segmentation than our method. Furthermore, our method achieves a Dice score that is at least 20% higher than the Dice scores of other compared methods when tumor volumes are less than 20 cm Conclusions: Experimental results demonstrate that the framework significantly outperforms the compared state-of-the-art methods, with decreased under- or over-segmentation and better small tumor identification. It has the potential for clinical application.
MeSH term(s)	Female ; Humans ; Bayes Theorem ; Uncertainty ; Ovarian Neoplasms/diagnostic imaging ; Learning ; Benchmarking ; Image Processing, Computer-Assisted
Language	English
Publishing date	2023-10-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	188780-4
ISSN	2473-4209 ; 0094-2405
ISSN (online)	2473-4209
ISSN	0094-2405
DOI	10.1002/mp.16795
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Zs.A 1210: Show issues

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Article ; Online: WMDS.net: a network control framework for identifying key players in transcriptome programs.

Cheng, Xiang / Amanullah, Md / Liu, Weigang / Liu, Yi / Pan, Xiaoqing / Zhang, Honghe / Xu, Haiming / Liu, Pengyuan / Lu, Yan

Bioinformatics (Oxford, England)

2023 Volume 39, Issue 2

Abstract: Motivation: Mammalian cells can be transcriptionally reprogramed to other cellular phenotypes. Controllability of such complex transitions in transcriptional networks underlying cellular phenotypes is an inherent biological characteristic. This network ... ...

Abstract	Motivation: Mammalian cells can be transcriptionally reprogramed to other cellular phenotypes. Controllability of such complex transitions in transcriptional networks underlying cellular phenotypes is an inherent biological characteristic. This network controllability can be interpreted by operating a few key regulators to guide the transcriptional program from one state to another. Finding the key regulators in the transcriptional program can provide key insights into the network state transition underlying cellular phenotypes. Results: To address this challenge, here, we proposed to identify the key regulators in the transcriptional co-expression network as a minimum dominating set (MDS) of driver nodes that can fully control the network state transition. Based on the theory of structural controllability, we developed a weighted MDS network model (WMDS.net) to find the driver nodes of differential gene co-expression networks. The weight of WMDS.net integrates the degree of nodes in the network and the significance of gene co-expression difference between two physiological states into the measurement of node controllability of the transcriptional network. To confirm its validity, we applied WMDS.net to the discovery of cancer driver genes in RNA-seq datasets from The Cancer Genome Atlas. WMDS.net is powerful among various cancer datasets and outperformed the other top-tier tools with a better balance between precision and recall. Availability and implementation: https://github.com/chaofen123/WMDS.net. Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	Animals ; Algorithms ; Transcriptome ; Neoplasms/genetics ; Oncogenes ; Gene Regulatory Networks ; Mammals/genetics
Language	English
Publishing date	2023-02-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btad071
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Zs.A 2374: Show issues

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Article ; Online: Linc00673-V3 positively regulates autophagy by promoting Smad3-mediated

Ni, Heng / Tang, Song / Lu, Guang / Niu, Yuequn / Xu, Jinming / Zhang, Honghe / Hu, Jian / Shen, Han-Ming / Wu, Yihua / Xia, Dajing

Life science alliance

2024 Volume 7, Issue 6

Abstract: Since its first discovery, long noncoding RNA Linc00673 has been linked to carcinogenesis and metastasis of various human cancers. Linc00673 had five transcriptional isoforms and their biological functions remained to be explored. Here we have reported ... ...

Abstract	Since its first discovery, long noncoding RNA Linc00673 has been linked to carcinogenesis and metastasis of various human cancers. Linc00673 had five transcriptional isoforms and their biological functions remained to be explored. Here we have reported that Linc00673-V3, one of the isoforms of Linc00673, promoted non-small cell lung cancer chemoresistance, and increased Linc00673-V3 expression level was associated with enhanced autophagy. Mechanistically, we discerned the existence of a stem-loop configuration engendered by the 1-100-nt and 2200-2275-nt fragments within Linc00673-V3. This structure inherently interacted with Smad3, thereby impeding its ubiquitination and subsequent degradation orchestrated by E3 ligase STUB1. The accumulation of Smad3 contributed to autophagy via up-regulation of
MeSH term(s)	Humans ; Autophagy ; Carcinoma, Non-Small-Cell Lung/metabolism ; Carcinoma, Non-Small-Cell Lung/pathology ; Cell Line, Tumor ; Cell Proliferation ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Protein Isoforms ; Ubiquitin-Protein Ligases ; RNA, Long Noncoding/metabolism ; Smad3 Protein/metabolism ; Microtubule-Associated Proteins/metabolism
Chemical Substances	Protein Isoforms ; STUB1 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; long non-coding RNA SLNCR1, human ; RNA, Long Noncoding ; SMAD3 protein, human ; Smad3 Protein ; MAP1LC3B protein, human ; Microtubule-Associated Proteins
Language	English
Publishing date	2024-03-25
Publishing country	United States
Document type	Journal Article
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.202302408
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Article ; Online: Wemics: A Single-Base Resolution Methylation Quantification Method for Enhanced Prediction of Epigenetic Regulation.

Liu, Yi / Yi, Jiani / Wu, Pin / Zhang, Jun / Li, Xufan / Li, Jia / Zhou, Liyuan / Liu, Yong / Xu, Haiming / Chen, Enguo / Zhang, Honghe / Liang, Mingyu / Liu, Pengyuan / Pan, Xiaoqing / Lu, Yan

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

2024 , Page(s) e2308884

Abstract: DNA methylation, an epigenetic mechanism that alters gene expression without changing DNA sequence, is essential for organism development and key biological processes like genomic imprinting and X-chromosome inactivation. Despite tremendous efforts in ... ...

Abstract	DNA methylation, an epigenetic mechanism that alters gene expression without changing DNA sequence, is essential for organism development and key biological processes like genomic imprinting and X-chromosome inactivation. Despite tremendous efforts in DNA methylation research, accurate quantification of cytosine methylation remains a challenge. Here, a single-base methylation quantification approach is introduced by weighting methylation of consecutive CpG sites (Wemics) in genomic regions. Wemics quantification of DNA methylation better predicts its regulatory impact on gene transcription and identifies differentially methylated regions (DMRs) with more biological relevance. Most Wemics-quantified DMRs in lung cancer are epigenetically conserved and recurrently occurred in other primary cancers from The Cancer Genome Atlas (TCGA), and their aberrant alterations can serve as promising pan-cancer diagnostic markers. It is further revealed that these detected DMRs are enriched in transcription factor (TF) binding motifs, and methylation of these TF binding motifs and TF expression synergistically regulate target gene expression. Using Wemics on epigenomic-transcriptomic data from the large lung cancer cohort, a dozen novel genes with oncogenic potential are discovered that are upregulated by hypomethylation but overlooked by other quantification methods. These findings increase the understanding of the epigenetic mechanism by which DNA methylation regulates gene expression.
Language	English
Publishing date	2024-03-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2808093-2
ISSN	2198-3844 ; 2198-3844
ISSN (online)	2198-3844
ISSN	2198-3844
DOI	10.1002/advs.202308884
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Article: Anti-Tumor Effect of Vitamin D Combined with Calcium on Lung Cancer: A Systematic Review and Meta-Analysis

Sun, Kang / Zuo, Minghao / Zhang, Qin / Wang, Keyi / Huang, Dongdong / Zhang, Honghe

Nutrition and cancer. 2021 Dec. 31, v. 73, no. 11-12

2021

Abstract: Although many studies have demonstrated the impact of vitamin D and calcium on lung cancer, it remains the discrepancy for the effect of vitamin D and calcium on lung cancer. In this study, we aimed to verify the roles of vitamin D and calcium in the ... ...

Abstract	Although many studies have demonstrated the impact of vitamin D and calcium on lung cancer, it remains the discrepancy for the effect of vitamin D and calcium on lung cancer. In this study, we aimed to verify the roles of vitamin D and calcium in the incidence and prognosis of lung cancer. A systematic literature search was performed by February 29, 2020. The relative risks (RRs) and hazard ratio (HRs) were pooled to evaluate the risk for the incidence and mortality of lung cancer. A total of 58,625 lung cancer cases from 40 studies were included. The risk (RR: 0.915, 95% Cl: 0.849–0.986) and mortality (RR: 0.718, 95% Cl: 0.530–0.973) of lung cancer were significantly decreased due to high circulating 25(OH)D level. Although the separate intake of vitamin D (RR: 0.909, 95% Cl: 0.801–1.031) and calcium (RR: 0.890, 95% Cl: 0.741–1.070) did not exhibit a protective effect on lung cancer, the combination supplement of vitamin D and calcium significantly decreased the incidence of lung cancer (RR: 0.811, 95% Cl: 0.659–0.999). High level of serum 25(OH)D could play the preventive role in lung cancer. Furthermore, vitamin D could be supplemented together with calcium against lung cancer.
Keywords	antineoplastic activity ; blood serum ; calcium ; hazard ratio ; lung neoplasms ; meta-analysis ; mortality ; prognosis ; protective effect ; risk assessment ; systematic review
Language	English
Dates of publication	2021-1231
Size	p. 2633-2642.
Publishing place	Taylor & Francis
Document type	Article
ZDB-ID	424433-3
ISSN	1532-7914 ; 0163-5581
ISSN (online)	1532-7914
ISSN	0163-5581
DOI	10.1080/01635581.2020.1850812
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 1496: Show issues

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Article ; Online: The expression of ADAMTS14 is regulated by promoter DNA methylation and is associated with poor prognosis in colorectal cancer.

Wang, Yan / Zhou, Jing / Zhang, Jing / Cao, Hui / Han, Fengyan / Zhang, Honghe / Xu, Enping

Experimental cell research

2021 Volume 410, Issue 1, Page(s) 112953

Abstract: Colorectal cancer (CRC) is one of the most common malignant tumors of digestive system, and its main cause of death is tumor metastasis. The occurrence of CRC is a polygenic and multi-step complex process involving genetic and epigenetic alterations. It ... ...

Abstract	Colorectal cancer (CRC) is one of the most common malignant tumors of digestive system, and its main cause of death is tumor metastasis. The occurrence of CRC is a polygenic and multi-step complex process involving genetic and epigenetic alterations. It has been demonstrated that ADAMTS14 (A disintegrin and metalloproteinase with thrombospondin motifs 14) was hypermethylated in esophageal cancer using whole-genome methylation microarray in our previous report. The present study revealed that ADAMTS14 was highly methylated accompanied with low expression in CRC. In addition, demethylation agent 5-Aza-dC could demethylate ADAMTS14 promoter region and reactivate ADAMTS14 expression effectively in vitro. Therefore, promoter hypermethylation was probably contributed to ADAMTS14 epigenetic silencing in CRC. Furthermore, ADAMTS14 protein expression was higher at invasive tumor front than at the tumor center or other areas of tumor. Kaplan-meier survival analysis indicated that the high ADAMTS14 expression was correlated with poor prognosis in CRC patients, suggesting the possibility that ADAMTS14 is a promising indicator in the evaluation of CRC prognosis.
MeSH term(s)	ADAMTS Proteins/genetics ; Aged ; Biomarkers, Tumor/genetics ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; DNA Methylation/genetics ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic/genetics ; HCT116 Cells ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Promoter Regions, Genetic/genetics
Chemical Substances	Biomarkers, Tumor ; ADAMTS Proteins (EC 3.4.24.-) ; ADAMTS14 protein, human (EC 3.4.24.-)
Language	English
Publishing date	2021-11-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1493-x
ISSN	1090-2422 ; 0014-4827
ISSN (online)	1090-2422
ISSN	0014-4827
DOI	10.1016/j.yexcr.2021.112953
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Zs.A 563: Show issues

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Article ; Online: Sequestosome 1/p62: A multitasker in the regulation of malignant tumor aggression (Review).

Tang, Jinlong / Li, Yuan / Xia, Shuli / Li, Jinfan / Yang, Qi / Ding, Kefeng / Zhang, Honghe

International journal of oncology

2021 Volume 59, Issue 4

Abstract: Sequestosome 1 (SQSTM1)/p62 is an adapter protein mainly involved in the transportation, degradation and destruction of various proteins that cooperates with components of autophagy and the ubiquitin‑proteasome degradation pathway. Numerous studies have ... ...

Abstract	Sequestosome 1 (SQSTM1)/p62 is an adapter protein mainly involved in the transportation, degradation and destruction of various proteins that cooperates with components of autophagy and the ubiquitin‑proteasome degradation pathway. Numerous studies have shown that SQSTM1/p62 functions at multiple levels, including involvement in genetic stability or modification, post‑transcriptional regulation and protein function. As a result, SQSTM1/p62 is a versatile protein that is a critical core regulator of tumor cell genetic stability, autophagy, apoptosis and other forms of cell death, malignant growth, proliferation, migration, invasion, metastasis and chemoradiotherapeutic response, and an indicator of patient prognosis. SQSTM1/p62 regulates these processes via its distinct molecular structure, through which it participates in a variety of activating or inactivating tumor‑related and tumor microenvironment‑related signaling pathways, particularly positive feedback loops and epithelial‑mesenchymal transition‑related pathways. Therefore, functioning as a proto‑oncogene or tumor suppressor gene in various types of cancer and tumor‑associated microenvironments, SQSTM1/p62 is capable of promoting or retarding malignant tumor aggression, giving rise to immeasurable effects on tumor occurrence and development, and on patient treatment and prognosis.
MeSH term(s)	Aggression ; Epithelial-Mesenchymal Transition ; Humans ; Neoplasms/etiology ; Neoplasms/pathology ; Sequestosome-1 Protein/genetics ; Sequestosome-1 Protein/physiology ; Tumor Microenvironment
Chemical Substances	SQSTM1 protein, human ; Sequestosome-1 Protein
Language	English
Publishing date	2021-08-20
Publishing country	Greece
Document type	Journal Article ; Review
ZDB-ID	1154403-x
ISSN	1791-2423 ; 1019-6439
ISSN (online)	1791-2423
ISSN	1019-6439
DOI	10.3892/ijo.2021.5257
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Zs.A 3690: Show issues

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Article ; Online: Methylation status of ADAM12 promoter are associated with its expression levels in colorectal cancer.

Wang, Yan / Zhang, Jing / Cao, Hui / Han, Fengyan / Zhang, Honghe / Xu, Enping

Pathology, research and practice

2021 Volume 221, Page(s) 153449

Abstract: Background: Colorectal cancer (CRC) is a kind of malignant tumor of digestive system severely affecting human health. The occurrence of CRC is a polygenic and multi-step complex process involving genetic and epigenetic alterations. ADAM12 (a disintegrin ...

Abstract	Background: Colorectal cancer (CRC) is a kind of malignant tumor of digestive system severely affecting human health. The occurrence of CRC is a polygenic and multi-step complex process involving genetic and epigenetic alterations. ADAM12 (a disintegrin and metalloproteases 12), is a gene that was commonly hypermethylated in esophageal cancer using whole-genome methylation microarray in our previous study. Methods: We detected the methylation frequencies of the CpG island in ADAM12 promoter using bisulfite-pyrosequencing in CRC cell lines and tissue samples. The expression of ADAM12 was detected by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). A systematic and comprehensive analysis of relationship of DNA hypermethylation and ADAM12 expression in CRC was performed in our samples and TCGA database. Results: The expression of ADAM12 in hypermethylated cell lines was significantly lower than that in hypomethylated cell lines, and demethylation agent 5-Aza-dC could demethylate ADAM12 promoter region and reactivate ADAM12 expression effectively. In 74 pairs of colorectal cancer and normal tissues, bisulfite-pyrosequencing results showed significantly hypermethylation of ADAM12 in CRC compared with adjacent normal mucosa, accompanied with lower expression of ADAM12 in CRC tissues compared to that of the normal tissues. In addition, there was a statistically significant negative correlation between ADAM12 protein expression and methylation levels (rho =-0.28, p = 0.015). Conclusion: Promoter hypermethylation was probably a mechanism of ADAM12 epigenetic silencing in CRC.
MeSH term(s)	ADAM12 Protein/genetics ; ADAM12 Protein/metabolism ; Adult ; Aged ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; DNA Methylation/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Male ; Middle Aged ; Promoter Regions, Genetic/genetics
Chemical Substances	ADAM12 Protein (EC 3.4.24.-) ; ADAM12 protein, human (EC 3.4.24.-)
Language	English
Publishing date	2021-04-15
Publishing country	Germany
Document type	Journal Article
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2021.153449
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