RNA Helicase DHX37 Facilitates Liver Cancer Progression by Cooperating with PLRG1 to Drive Superenhancer-Mediated Transcription of Cyclin D1

Liu, Zhen; Ye, Youqiong; Liu, Yizhe; Liu, Yanfang; Chen, Huifang; Shen, Mengting; Wang, Zhen; Huang, Shenglin; Han, Leng; Chen, Zhiao; He, Xiang

doi:10.1158/0008-5472.can-21-3038

Cited by 14 publications

(14 citation statements)

References 42 publications

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Section: Discussionmentioning

confidence: 99%

“…CCND1 has been recognized as a oncogene, and overexpression of CCND1 can lead to uncontrolled cell proliferation. Studies have shown that overexpression of the CCND1 has been identified in various cancers, including breast cancer, bladder cancer, and lung cancer [15,16]. 10 Disease Markers exhibited decreased PI3K, AKT, mTOR, and CCND1 mRNA levels as well as reduced p-PI3K/PI3K, p-AKT/ AKT, p-mTOR/mTOR, and CCND1 protein levels and increased the expression of PTEN, suggesting that DDTC can drive apoptotic death via the inhibition of the PI3K/ AKT/mTOR signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

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DDTC Suppresses Ovarian Cancer Development via the PI3K/AKT/mTOR Signaling Pathway

Zhang

Wang

et al. 2022

Disease Markers

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In prior research, 6,12-diphenyl-3,9-diazatetraasterane-1, 5, 7, 11-tetracarboxylate (DDTC) has been shown to be an effective inhibitor of the growth of the SKOV3 and A2780 ovarian cancer (OC) cell lines. Flow cytometry analyses indicated that DDTC was able to suppress P-CNA expression at the protein level within OC cells, while RNA-seq indicated that DDTC treatment was associated with marked changes in gene expression profiles within A2780 cells. Molecular docking analyses suggested that DDTC has the potential to readily dock with key signaling proteins including PI3K, AKT, and mTOR. In line with these findings, DDTC treatment inhibited the growth of xenograft tumors in a mouse model system. Such treatment was also associated with reduced p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, and CyclinD1 (CCND1) expressions and with the increased expression of PTEN in vitro and in vivo. Together, these results suggest that DDTC is capable of readily inhibiting OC development at least in part via targeting and modulating signaling via the PI3K/AKT/mTOR axis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

DDTC Suppresses Ovarian Cancer Development via the PI3K/AKT/mTOR Signaling Pathway

Zhang

Wang

et al. 2022

Disease Markers

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“…Mutations and dysregulation of Dhx37 impact the prognosis of hepatocellular carcinoma and lung adenocarcinoma 70 . Although research has mainly focused on its potential as a carcinoma biomarker and its mechanistic function as an RNA helicase in the release of the U3 snoRNP from pre-ribosomal particles 71 , and activation by UTP14A in ribosome biogenesis 72 , our study creatively found the potential role of Dhx37 in cardiovascular disease.…”

Section: Discussionmentioning

confidence: 97%

A functional medicine and food homology composition discovery based on disease-related target and data mining against cardiac remodeling

Xiao,

Li,

Qin

et al. 2024

Preprint

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Background: Medicine and food homological (MFH) products exhibit enhanced safety and tolerability, minimizing notable side effects, making them pivotal for prolonged use in cardiovascular diseases. This study aims to identify functional compounds in MFH based on cardiac remodeling-related target, employing reliable, comprehensive, and high-throughput methods. Methods: By bioinformatics and in vivo verifications, we initially investigated the key target in the progression of cardiac remodeling. Subsequently, we performed molecular docking among medical homology compound database (MHCD), and then performed drug-likeness evaluations to recognize functional component based on disease-related target. Pharmacological verifications and data mining including cardiac and medullary transcriptomics, neurotransmitter metabolomics, resting-state functional magnetic resonance imaging (rs-fMRI), and correlationship analysis were utilized to define the benefical effects of MFH functional components, as well as its in-depth mechanims. Results: The critical roles of oxidative stress and the key target of NRF2 in cardiac remodeling were discovered, and β-ecdysterone was screened as the most promising NRF2 enhancer in MHCD. Dose-dependent efficacy of β-ecdysterone in countering oxidative stress and ameliorating cardiac remodeling were then verfied by in vivo and ex vivo experiments. By data mining, the crosstalk mechanism between cardiac remodeling and neuromodulation was identified, and further unveiled Slc41a3 as a potential key factor influenced by β-ecdysterone. Additionally, β-ecdysterone mitigated increases in norepinephrine (NE) and its metabolites DHPG in the sympathetic nerve center hypothalamic paraventricular (PVN), as indicated by rs-fMRI. Cardiac and medullary transcriptomes revealed central-peripheral regulation signaling pathways during cardiac remodeling with the involvement of core gene of Dhx37. Conclusions: Our study identified β-ecdysterone as a natural MFH functional compound countering cardiac remodeling by targeting NRF2 elevation. It elucidates crosstalk between cardiac remodeling and neuromodulation, facilitating precise drug screening and mechanistic insights, providing substantial evidence for β-ecdysterone application and molecular mechanisms in cardiovascular diseases.

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“…Interestingly, some upregulated genes found in RNA processing ( MAGOH , SCAF11 and PLRG 1) have been shown to play a role in tumorigenesis and cancer aggressiveness in glioma, liver, and gastric cancers [ 28 , 29 , 30 ]. Upregulation of these genes may lead to an aberrant RNA splicing and promote splice-induced gene alterations, such as the Delta11q mutation within the BRCA1 gene [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Development of Olaparib-Resistance Prostate Cancer Cell Lines to Identify Mechanisms Associated with Acquired Resistance

Cahuzac

Péant

Mes-Masson

et al. 2022

Cancers

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Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) were initially deployed to target breast and ovarian tumors with mutations in DNA damage response genes. Recently, PARPi have been shown to be beneficial in the treatment of prostate cancer (PC) patients having exhausted conventional therapeutics. Despite demonstrating promising response rates, all patients treated with PARPi eventually develop resistance. However, PARPi resistance in PC is not well understood, and further studies are required to understand PARPi resistance in PC to propose strategies to circumvent resistance. Methods: Starting from well-established olaparib-sensitive PC cell lines (LNCaP, C4-2B and DU145), we derived olaparib-resistant (OR) PC cell lines and performed a microarray analysis. Results: The olaparib IC50 values of OR cell lines increased significantly as compared to the parental cell lines. Gene expression analyses revealed that different pathways, including DNA repair, cell cycle regulation and autophagy, were affected by acquired resistance. A total of 195 and 87 genes were significantly upregulated and downregulated, respectively, in all three OR cell lines compared to their parental counterparts. Among these genes, we selected BRCC3, ROCK2 and ATG2B for validation. We showed that ROCK2 expression, basal autophagy and homologous recombination (HR) efficiency were increased in all OR cell lines. Conclusions: Our study provides a new in vitro model to study PARPi resistance in PC and suggests new possible targets to reverse resistance and prolong the benefits of PARPi treatment.

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RNA Helicase DHX37 Facilitates Liver Cancer Progression by Cooperating with PLRG1 to Drive Superenhancer-Mediated Transcription of Cyclin D1

Cited by 14 publications

References 42 publications

DDTC Suppresses Ovarian Cancer Development via the PI3K/AKT/mTOR Signaling Pathway

DDTC Suppresses Ovarian Cancer Development via the PI3K/AKT/mTOR Signaling Pathway

A functional medicine and food homology composition discovery based on disease-related target and data mining against cardiac remodeling

Development of Olaparib-Resistance Prostate Cancer Cell Lines to Identify Mechanisms Associated with Acquired Resistance

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