4.4 Article

miR-143-3p represses leukemia cell proliferation by inhibiting KAT6A expression

Journal

ANTI-CANCER DRUGS
Volume 33, Issue 1, Pages E662-E669

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CAD.0000000000001231

Keywords

acute myeloid leukemia; MiR-143-3p; KAT6A; proliferation

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This study investigates the expressions and interactions of miR-143-3p and KAT6A in acute myeloid leukemia (AML). The results show that high expression of KAT6A is associated with the viability and proliferation of AML cells, while overexpression of miR-143-3p can inhibit the viability and proliferation of AML cells. Furthermore, there is a functional interaction between KAT6A and miR-143-3p. Overall, miR-143-3p and KAT6A play important roles in the viability and proliferation of AML cells.
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. 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. 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-1 beta, TNF-alpha and IL-6, and increased the expression levels of TGF-beta 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. miR-143-3p/KAT6A played an essential role in the viability and proliferation of AML cells.

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