Evidence map›Paper›PMID 31752390›Full record

ArticleCells2019

Suppression of Angiogenesis by Targeting Cyclin-Dependent Kinase 7 in Human Umbilical Vein Endothelial Cells and Renal Cell Carcinoma: An In Vitro and In Vivo Study.

Chung-Sheng Shi, Kuan-Lin Kuo, Mei-Sin Chen, Po-Ming Chow, Shing-Hwa Liu, Yu-Wei Chang, Wei-Chou Lin, Shih-Ming Liao, Chen-Hsun Hsu, Fu-Shun Hsu and 2 more

Abstract read
In one paragraph

Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Chung-Sheng ShiGraduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.ORCID 0000-0002-5548-7675
Kuan-Lin KuoDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei 100, Taiwan.
Mei-Sin ChenGraduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Po-Ming ChowDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei 100, Taiwan.
Shing-Hwa LiuGraduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.ORCID 0000-0002-9976-1197
Yu-Wei ChangDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei 100, Taiwan.
Wei-Chou LinDepartment of Pathology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei 100, Taiwan.
Shih-Ming LiaoDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei 100, Taiwan.
Chen-Hsun HsuDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei 100, Taiwan.
Fu-Shun HsuGraduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 106, Taiwan.ORCID 0000-0002-4586-7308
Hong-Chiang ChangDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei 100, Taiwan.
Kuo-How HuangDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei 100, Taiwan.ORCID 0000-0002-0989-0578

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer cells rely on aberrant transcription for growth and survival. Cyclin-dependent kinases (CDKs) play critical roles in regulating gene transcription by modulating the activity of RNA polymerase II (RNAPII). THZ1, a selective covalent inhibitor of CDK7, has antitumor effects in several human cancers. In this study, we investigated the role and therapeutic potential of CDK7 in regulating the angiogenic activity of endothelial cells and human renal cell carcinoma (RCC). Our results revealed that vascular endothelial growth factor (VEGF), a critical activator of angiogenesis, upregulated the expression of CDK7 and RNAPII, and the phosphorylation of RNAPII at serine 5 and 7 in human umbilical vein endothelial cells (HUVECs), indicating the transcriptional activity of CDK7 may be involved in VEGF-activated angiogenic activity of endothelium. Furthermore, through suppressing CDK7 activity, THZ1 suppressed VEGF-activated proliferation and migration, as well as enhanced apoptosis of HUVECs. Moreover, THZ1 inhibited VEGF-activated capillary tube formation and CDK7 knockdown consistently diminished tube formation in HUVECs. Additionally, THZ1 reduced VEGF expression in human RCC cells (786-O and Caki-2), and THZ1 treatment inhibited tumor growth, vascularity, and angiogenic marker (CD31) expression in RCC xenografts. Our results demonstrated that CDK7-mediated transcription was involved in the angiogenic activity of endothelium and human RCC. THZ1 suppressed VEGF-mediated VEGFR2 downstream activation of angiogenesis, providing a new perspective for antitumor therapy in RCC patients.

Indexed as

AnimalsCarcinoma, Renal CellCell Line, TumorCell MovementCell ProliferationCyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesDisease Models, AnimalHumansHuman Umbilical Vein Endothelial CellsKidney NeoplasmsMiceNeovascularization, PathologicProtein Kinase InhibitorsXenograft Model Antitumor AssaysCyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesProtein Kinase Inhibitorsangiogenesiscyclin-dependent kinase 7endothelial cellrenal cell carcinomaTHZ1

Identifiers

PMID31752390
PMCPMC6912535

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.