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Tytuł pozycji:

LncRNA-CCDC144NL-AS1 Promotes the Development of Hepatocellular Carcinoma by Inducing WDR5 Expression via Sponging miR-940

Tytuł:
LncRNA-CCDC144NL-AS1 Promotes the Development of Hepatocellular Carcinoma by Inducing WDR5 Expression via Sponging miR-940
Autorzy:
Zhang Y
Zhang H
Wu S
Temat:
long non-coding rna ccdc144nl-as1
wd repeat domain 5
matrix metalloproteinase
cyclin-dependent kinase
prognosis
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Źródło:
Journal of Hepatocellular Carcinoma, Vol Volume 8, Pp 333-348 (2021)
Wydawca:
Dove Medical Press, 2021.
Rok publikacji:
2021
Kolekcja:
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Typ dokumentu:
article
Opis pliku:
electronic resource
Język:
English
ISSN:
2253-5969
Relacje:
https://www.dovepress.com/lncrna-ccdc144nl-as1-promotes-the-development-of-hepatocellular-carcin-peer-reviewed-fulltext-article-JHC; https://doaj.org/toc/2253-5969
Dostęp URL:
https://doaj.org/article/2d0f67ab0bea4bb89fe209fe3f78a578  Link otwiera się w nowym oknie
Numer akcesji:
edsdoj.2d0f67ab0bea4bb89fe209fe3f78a578
Czasopismo naukowe
Yingying Zhang, Hongyu Zhang, Shuhuan Wu Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Shuhuan WuDepartment of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, Henan, 450052, People’s Republic of ChinaTel +86-371-67966952Fax +86-371-67966952Email fcczhanghy@zzu.edu.cnPurpose: This work was initiated to offer solid evidence regarding the expression and roles of long noncoding RNA (lncRNA) CCDC144NL-AS1 in hepatocellular carcinoma (HCC).Patients and Methods: Cell Counting Kit-8 assay, flow cytometric analysis, and invasion assays were used to explore the malignant biological characteristics of cells. Immunohistochemistry (IHC), Western blotting analysis, and real-time quantitative PCR (RT-qPCR) were used to analyze the expression level of related proteins and nucleic acids. Bl6/Rag2/GammaC double knockout mice were used for HCC modeling to address the therapeutic value of CCDC144NL-AS1.Results: CCDC144NL-AS1 was significantly upregulated in HCC tissue and had a marked relationship with the 5-year prognosis. In vitro study revealed that CCDC144NL-AS1 was highly expressed in HCC cell line MHCC97H but lowly expressed in normal hepatic cell line L02. Overexpression of CCDC144NL-AS1 in L02 enhanced the invasion and proliferation abilities of cells but inhibited the apoptosis rate. Knockdown of CCDC144NL-AS1 in MHCC97H weakened the invasion and proliferation abilities of cells but increased the apoptosis rate. CCDC144NL-AS1 was found to sponge miR-940 to induce the expression of WD repeat domain 5 (WDR5). ChIP-seq analysis identified that matrix metalloproteinase (MMP) 2, MMP9, and cyclin-dependent kinase (CDK) 1, CDK2, and CDK4 were all targets of WDR5. The recruitment of WDR5 to the promoter of these target genes upregulated the histone H3 lysine 4 trimethylation (H3K4me3) level in these regions and further induced the transcription of MMP2, MMP9, CDK1, CDK2, and CDK4. In vivo study revealed that compared to the normal liver tissue, CCDC144NL-AS1, WDR5, MMP2, MMP9, CDK1, CDK2, and CDK4 were all significantly upregulated in HCC tissue from the same mouse, while miR-940 was decreased. Besides, knockdown of CCDC144NL-AS1 or WDR5 or overexpression of miR-940 could all inhibit tumor growth.Conclusion: CCDC144NL-AS1 drives HCC development by inducing MMP2/MMP9 and CDK1/CDK2/CDK4 expressions through miR-940/WDR5-regulated epigenetic pathway.Keywords: long non-coding RNA CCDC144NL-AS1, WD repeat domain 5, matrix metalloproteinase, cyclin-dependent kinase, prognosis

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