miR-143-3p represses leukemia cell proliferation by inhibiting KAT6A expression
Autor: | Jinlong Jiang, Chengfu Ji, Guangsheng He, Dan Xu, Haixia Zhou |
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Rok vydání: | 2021 |
Předmět: |
Cancer Research
proliferation Down-Regulation Apoptosis acute myeloid leukemia KAT6A Clinical Reports Flow cytometry Transforming Growth Factor beta Cell Line Tumor hemic and lymphatic diseases medicine Humans Pharmacology (medical) neoplasms Cell Proliferation Histone Acetyltransferases Pharmacology Reporter gene Gene knockdown medicine.diagnostic_test biology Tumor Necrosis Factor-alpha Chemistry Cell growth Interleukins Myeloid leukemia medicine.disease Up-Regulation Proliferating cell nuclear antigen Leukemia Myeloid Acute MicroRNAs Leukemia Oncology Cell culture Gene Knockdown Techniques MiR-143-3p Cancer research biology.protein |
Zdroj: | Anti-Cancer Drugs |
ISSN: | 0959-4973 |
DOI: | 10.1097/cad.0000000000001231 |
Popis: | Objective The present study is designed to investigate the expressions of microRNA-143-3p (miR-143-3p) and Lysine acetyltransferase 6A (KAT6A) in acute myeloid leukemia (AML) samples and AML cell lines and to explore the possible effects and underlying mechanisms of miR-143-3p on the proliferation of AML cells. Methods The expressions of miR-143-3p and KAT6A in AML samples and cell lines were detected by RT-qPCR assay. CCK-8 and flow cytometry were performed to evaluate the role of KAT6A in viability of AML cells. EdU assay was performed to determine the effects of KAT6A on proliferation of AML cells. Western blot analysis was utilized to assess the impacts of KAT6A on proliferation-related protein expressions of AML cells. ELISA assay was adopted to illustrate the influence of KAT6A on inflammatory responses of AML cells. In addition, the relationship between KAT6A and miR-143-3p was predicted by ENCORI and miRWalk, and confirmed by dual-luciferase reporter assay. Moreover, the effects of KAT6A on the proliferation of AML cells mediated with miR-143-3p were carried out by rescue experiment. Results The expression of KAT6A was significantly upregulated, while miR-134-4p was downregulated both in the AML tissues and in AML cell lines. In addition, the silence of KAT6A significantly inhibited the viability of AML cells. Besides, KAT6A silencing notably suppressed the proliferation of AML cells and reduced the protein expressions of Ki-67 and PCNA. Knockdown of KAT6A notably decreased the expression levels of IL-1β, TNF-α and IL-6, and increased the expression levels of TGF-β and IL-10. Moreover, overexpression of miR-143-3p repressed viability and proliferation of AML cells and overexpression of KAT6A partially reversed the inhibitory effects of miR-143-3p mimic on viability and proliferation of AML cells. Conclusion miR-143-3p/KAT6A played an essential role in the viability and proliferation of AML cells. |
Databáze: | OpenAIRE |
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