Cyclin-dependent kinase 19 upregulation correlates with an unfavorable prognosis in hepatocellular carcinoma

Abstract Objectives Cyclin-dependent kinase 19 (CDK19) is a component of the mediator coactivator complex, which is required for transcriptional activation. In this study, we utilized public databases and wet-bench hepatic cell line experiments 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 to HCC via the Oncomine and UALCAN databases. The prognostic value of CDK19 was tested using the Kaplan–Meier Plotter database. We presented the mutations of CDK19 and addressed the relation of CDK19 expression with immune cell infiltration by means of the cBioPortal, Catalogue of Somatic Mutations in Cancer (COSMIC) and Tumor IMmune Estimation Resource (TIMER) databases. Hub genes were obtained and further analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. To test the in silico findings, we knocked down CDK19 with short hairpin RNA (shRNA) technology in two hepatic cell lines and conducted several functional characterization experiments. Results Marked CDK19 upregulation was found in HCC tissues versus normal liver tissues, and CDK19 mRNA expression had high diagnostic value in HCC patients. Subgroup analysis showed that CDK19 overexpression was associated with sex, tumor stage and TP53 mutation status. The prognostic value of CDK19 upregulation for overall survival (OS) was significant in patients with stage 2–3, stage 3–4, and grade 2 disease. One percent of the patients had CDK19 mutations, but no relationship between CDK19 mutation and prognosis was observed. CDK19 was positively correlated with the abundances of CD4 + T cells, macrophages and dendritic cells. We identified 10 genes correlated with CDK19, 8 of which presented excellent prognostic value in HCC. These hub genes were directly involved in cell division and regulation of the G2/M cell cycle transition. Protein–protein interaction (PPI) and pathway predictions indicated that CDK19 is highly likely to be involved in several cellular functions, such as proliferation, migration, and invasion. These functions were strongly interfered from two independent hepatic cell lines after CDK19 knockdown. Conclusions CDK19 could be a prognostic marker in HCC, and its therapeutic potential in HCC needs further study.

Download Full-text

Cyclin Dependent Kinase 19 Upregulation Correlates With Unfavorable Prognosis in Hepatocellular Carcinoma

10.21203/rs.3.rs-445045/v1 ◽

2021 ◽

Author(s):

Xiaopeng Cai ◽

Jingwen Deng ◽

Jiaming zhou ◽

Huiqiang Cai ◽

Zhi Chen

Keyword(s):

Cell Lines ◽

Transcriptional Activation ◽

Prognostic Value ◽

Functional Characterization ◽

Hepatic Cell ◽

Migration And Invasion ◽

Cyclin Dependent Kinase ◽

Hub Genes ◽

Public Data ◽

Hepatic Cell Lines

Abstract 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.

Download Full-text

Functional characterization of ATP7B mutant hepatic cell lines after copper exposure

Journal of Gastrointestinal & Digestive System ◽

10.4172/2161-069x.c1.032 ◽

2016 ◽

Vol 06 (03) ◽

Author(s):

Hartmut Schmidt

Keyword(s):

Cell Lines ◽

Functional Characterization ◽

Hepatic Cell ◽

Copper Exposure ◽

Hepatic Cell Lines

Download Full-text

Cytotoxicity of anisidine in hepatic cell lines

Zeitschrift für Gastroenterologie ◽

10.1055/s-0034-1397131 ◽

2015 ◽

Vol 53 (01) ◽

Author(s):

S Caliskan ◽

F Wewering ◽

B Gerding ◽

A Luch ◽

S Zellmer

Keyword(s):

Cell Lines ◽

Hepatic Cell ◽

Hepatic Cell Lines

Download Full-text

Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer

Cells ◽

10.3390/cells10071820 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1820

Author(s):

Chengcheng Hao ◽

Yuxin Cui ◽

Jane Lane ◽

Shuqin Jia ◽

Jiafu Ji ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Prognostic Value ◽

Splice Variants ◽

Tnm Staging ◽

Migration And Invasion ◽

Ros Production ◽

Gastric Cancer Cells ◽

Normal Tissues

Background: Osteopontin (OPN) splice variants are identified as predictors of tumour progression and therapeutic resistance in certain types of solid tumours. However, their roles in gastric cancer (GC) remain poorly characterized. The current study sought to assess the prognostic value of the three OPN splice variants (namely OPN-a, OPN-b, and OPN-c) in gastric cancer and their potential functions within gastric cancer cells. Methods: RNA extraction and reverse transcription were performed using our clinical cohort of gastric carcinomas and matched normal tissues (n = 324 matched pairs). Transcript levels were determined using real-time quantitative PCR. Three OPN splice variants overexpressed cell lines were created from the gastric cancer cell line HGC-27. Subsequently, biological functions, including cell growth, adhesion, migration, and invasion, were studied. The potential effects of OPN isoforms on cisplatin and 5-Fu were evaluated by detecting cellular reactive oxygen species (ROS) levels in the HGC-27-derived cell lines. Results: Compared with normal tissues, the expression levels of three splice variants were all elevated in gastric cancer tissues in an order of OPN-a > OPN-b > OPN-c. The OPN-a level significantly increased with increasing TNM staging and worse clinical outcome. There appeared to be a downregulation for OPN-c in increasing lymph node status (p < 0.05), increasing TNM staging, and poor differentiation. High levels of OPN-a and OPN-b were correlated with short overall survival and disease-free survival of gastric cancer patients. However, the low expression of OPN-c was significantly associated with a poor prognosis. Functional analyses further showed that ectopic expression of OPN-c suppressed in vitro proliferation, adhesiveness, migration, and invasion properties of HGC-27 cells, while the opposite role was seen for OPN-a. Cellular ROS detection indicated that OPN-a and OPN-c significantly promoted ROS production after treatment with 5-Fu comparing to OPN-vector, while only OPN-a markedly induced ROS production after treatment with cisplatin. Conclusion: Our results suggest that OPN splice variants have distinguished potential to predict the prognosis of gastric cancer. Three OPN variants exert distinctive functions in gastric cancer cells. Focusing on specific OPN isoforms could be a novel direction for developing diagnostic and therapeutic approaches in gastric cancer.

Download Full-text

Plasmodium yoelii: Efficient in Vitro Invasion and Complete Development of Sporozoites in Mouse Hepatic Cell Lines

Experimental Parasitology ◽

10.1006/expr.2000.4570 ◽

2000 ◽

Vol 96 (4) ◽

pp. 257-259 ◽

Cited By ~ 18

Author(s):

Maria M Mota ◽

Ana Rodriguez

Keyword(s):

Cell Lines ◽

Plasmodium Yoelii ◽

Hepatic Cell ◽

Complete Development ◽

In Vitro Invasion ◽

Hepatic Cell Lines

Download Full-text

Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis

Biomolecules ◽

10.3390/biom11111605 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1605

Author(s):

Carlos Fernandes ◽

Afonso J. C. Videira ◽

Caroline D. Veloso ◽

Sofia Benfeito ◽

Pedro Soares ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Lines ◽

Mitochondrial Membrane ◽

Hepatic Cell ◽

Therapeutic Application ◽

Extracellular Acidification ◽

Mitochondrial Oxidative Stress ◽

Drug Candidates ◽

Cellular Oxygen ◽

Hepatic Cell Lines

Mitochondriotropic antioxidants (MC3, MC6.2, MC4 and MC7.2) based on dietary antioxidants and analogs (caffeic, hydrocaffeic, trihydroxyphenylpropanoic and trihydroxycinnamic acids) were developed. In this study, we evaluate and compare the cytotoxicity profile of novel mitochondria-targeted molecules (generally known as MitoCINs) on human HepG2 and differentiated SH-SY5Y cells with the quinone-based mitochondria-targeted antioxidants MitoQ and SkQ1 and with two non-targeted antioxidants, resveratrol and coenzyme Q10 (CoQ10). We further evaluate their effects on mitochondrial membrane potential, cellular oxygen consumption and extracellular acidification rates. Overall, MitoCINs derivatives reduced cell viability at concentrations about six times higher than those observed with MitoQ and SkQ1. A toxicity ranking for both cell lines was produced: MC4 < MC7.2 < MC3 < MC6.2. These results suggest that C-6 carbon linker and the presence of a pyrogallol group result in lower cytotoxicity. MC3 and MC6.2 affected the mitochondrial function more significantly relative to MitoQ, SkQ1, resveratrol and CoQ10, while MC4 and MC7.2 displayed around 100–1000× less cytotoxicity than SkQ1 and MitoQ. Based on the mitochondrial and cytotoxicity cellular data, MC4 and MC7.2 are proposed as leads that can be optimized to develop safe drug candidates with therapeutic application in mitochondrial oxidative stress-related diseases.

Download Full-text

Rapamycin Response in Tumorigenic and Non-Tumorigenic Hepatic Cell Lines

PLoS ONE ◽

10.1371/journal.pone.0007373 ◽

2009 ◽

Vol 4 (10) ◽

pp. e7373 ◽

Cited By ~ 15

Author(s):

Rosa H. Jimenez ◽

Joan M. Boylan ◽

Ju-Seog Lee ◽

Mirko Francesconi ◽

Gastone Castellani ◽

...

Keyword(s):

Cell Lines ◽

Hepatic Cell ◽

Hepatic Cell Lines

Download Full-text

Comparison of protein expression between human livers and the hepatic cell lines HepG2, Hep3B, and Huh7 using SWATH and MRM-HR proteomics: Focusing on drug-metabolizing enzymes

Drug Metabolism and Pharmacokinetics ◽

10.1016/j.dmpk.2018.03.003 ◽

2018 ◽

Vol 33 (2) ◽

pp. 133-140 ◽

Cited By ~ 21

Author(s):

Jian Shi ◽

Xinwen Wang ◽

Lingyun Lyu ◽

Hui Jiang ◽

Hao-Jie Zhu

Keyword(s):

Protein Expression ◽

Cell Lines ◽

Hepatic Cell ◽

Drug Metabolizing Enzymes ◽

Metabolizing Enzymes ◽

Human Livers ◽

Hepatic Cell Lines

Download Full-text

MicroRNA-99b predicts clinical outcome of osteosarcoma and suppresses tumor cell proliferation, migration and invasion

Diagnostic Pathology ◽

10.1186/s13000-019-0889-y ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 1

Author(s):

Xin Shi ◽

Xingfa Guan

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Prognostic Value ◽

Cox Regression ◽

Expression Profiles ◽

Migration And Invasion ◽

Aberrant Expression ◽

Cox Regression Analysis ◽

Normal Tissues

Abstract Background Osteosarcoma (OS) is a malignancy predominantly occurred in children and adolescents. Numerous microRNAs are involved in the pathogenesis of various cancers. This study aimed to investigate the expression profiles of miR-99b and its prognostic value in OS patients, and further analyze the biological function of miR-99b in the tumor progression by using OS cells. Methods Expression of miR-99b was measured using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were performed to evaluate the prognostic value of miR-99b. OS cell lines were used to investigate the effects of miR-99b on cell proliferation, migration and invasion. Results A significant decreased expression of miR-99b was observed in the OS tissues and cell lines respectively compared with the normal tissues and cells. Aberrant expression of miR-99b was associated with the patients’ metastasis and TNM stage, and could be used to predict the prognosis of OS. The expression of miR-99b was regulated in vitro by cell transfection, and we found that the overexpression of miR-99b led to suppressed cell proliferation, migration and invasion, whereas the knockdown of miR-99b resulted in the opposite results. Conclusions In one word, the aberrantly expressed miR-99b serves a prognostic biomarker for OS patients. OS cell proliferation, migration and invasion can be inhibited by the overexpression of miR-99b, suggesting that the methods to increase miR-99b expression may be novel therapeutic strategies in OS.

Download Full-text