This preprint is under consideration at BMC Gastroenterology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
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Research Article
Zhi Chen
Zhejiang University School of Medicine
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Objectives: Cyclin dependent kinase 19 (CDK19) is a component of the Mediator co-activator complex, which is required for transcriptional activation. In this study, we will utilize the public data and combine it with wet-bench experiments in hepatic cell lines to elucidate the potential roles of CDK19 in hepatocellular cancer (HCC).
Materials and Methods: We studied the relationships between CDK19 expression and several clinical features related with HCC by consulting Oncomine and UALCAN. The prognostic value of CDK19 was tested using the Kaplan‐Meier Plotter database. We presented the mutations of CDK19 and addressed its relations with immune cells with the use of cBioPortal, and COSMIC and TIMER database. Hub genes were obtained and further analysed using the STRING database. To test the in silico findings, we knocked down CDK19 with short hairpin RNA (shRNA) technology in two hepatic cell lines, and then several functional characterization experiments were conducted.
Results: A remarkably higher level of CDK19 expression was found in HCC tissues than normal liver tissues, and CDK19 mRNA expression has high diagnostic value in HCC patients. Subgroup analysis showed that CDK19 overexpression were associated with gender, tumor stage and TP53 mutant. Prognostic values of CDK19 upregulation for overall survival (OS) were significant in patients with stage 2-3, stage 3-4, grade 2 and etc. 1% of the patients have mutations at CDK19, and we did not observe a potential relationship between CDK19 mutation and prognosis. CDK19 showed positive correlations with the abundances of CD4+ T cells, macrophages and dendritic cells. We identified 10 genes that correlated with CDK19, 8 of which presented excellent prognostic value in HCC. Besides, these hub genes were directly involved in cell division and regulation of G2/M transition of mitotic cell cycle. PPI and pathway predictions indicated that CDK19 should have a high possibility to be involved with several cellular functions, such as proliferation, migration, and invasion. These functions were strongly interfered in two independent hepatic cell lines, after knocking down CDK19.
Conclusions: CDK19 could serve as a prognostic marker in HCC and it deserves further work to test its therapeutic potential to HCC.
Keywords
Cyclin dependent kinase 19, hepatocellular carcinoma, prognosis, knocking down, proliferation, migration, invasion
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No competing interests reported.
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This preprint is under consideration at BMC Gastroenterology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Zhi Chen
Zhejiang University School of Medicine
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 29 Apr, 2021
No community comments so far
Reviews received
Received 19 Jun, 2021
Reviewers agreed
On 29 May, 2021
Reviewers agreed
On 29 May, 2021
Reviewers invited
Invitations sent on 29 May, 2021
Editor assigned
On 29 May, 2021
Editor invited
On 27 Apr, 2021
Submission checks complete
On 27 Apr, 2021
First submitted
On 20 Apr, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Gastroenterology & Hepatology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Objectives: Cyclin dependent kinase 19 (CDK19) is a component of the Mediator co-activator complex, which is required for transcriptional activation. In this study, we will utilize the public data and combine it with wet-bench experiments in hepatic cell lines to elucidate the potential roles of CDK19 in hepatocellular cancer (HCC).
Materials and Methods: We studied the relationships between CDK19 expression and several clinical features related with HCC by consulting Oncomine and UALCAN. The prognostic value of CDK19 was tested using the Kaplan‐Meier Plotter database. We presented the mutations of CDK19 and addressed its relations with immune cells with the use of cBioPortal, and COSMIC and TIMER database. Hub genes were obtained and further analysed using the STRING database. To test the in silico findings, we knocked down CDK19 with short hairpin RNA (shRNA) technology in two hepatic cell lines, and then several functional characterization experiments were conducted.
Results: A remarkably higher level of CDK19 expression was found in HCC tissues than normal liver tissues, and CDK19 mRNA expression has high diagnostic value in HCC patients. Subgroup analysis showed that CDK19 overexpression were associated with gender, tumor stage and TP53 mutant. Prognostic values of CDK19 upregulation for overall survival (OS) were significant in patients with stage 2-3, stage 3-4, grade 2 and etc. 1% of the patients have mutations at CDK19, and we did not observe a potential relationship between CDK19 mutation and prognosis. CDK19 showed positive correlations with the abundances of CD4+ T cells, macrophages and dendritic cells. We identified 10 genes that correlated with CDK19, 8 of which presented excellent prognostic value in HCC. Besides, these hub genes were directly involved in cell division and regulation of G2/M transition of mitotic cell cycle. PPI and pathway predictions indicated that CDK19 should have a high possibility to be involved with several cellular functions, such as proliferation, migration, and invasion. These functions were strongly interfered in two independent hepatic cell lines, after knocking down CDK19.
Conclusions: CDK19 could serve as a prognostic marker in HCC and it deserves further work to test its therapeutic potential to HCC.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
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