Research Papers:

MiR-424 and miR-27a increase TRAIL sensitivity of acute myeloid leukemia by targeting PLAG1

Yan-ping Sun, Fei Lu, Xiao-yu Han, Min Ji, Ying Zhou, A-min Zhang, Hong-chun Wang, Dao-xin Ma and Chun-yan Ji _

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Oncotarget. 2016; 7:25276-25290. https://doi.org/10.18632/oncotarget.8252

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Yan-ping Sun1,*, Fei Lu1,*, Xiao-yu Han1, Min Ji1, Ying Zhou1, A-min Zhang1, Hong-chun Wang1, Dao-xin Ma1, Chun-yan Ji1

1Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China

*These authors contributed equally to this work

Correspondence to:

Chun-yan Ji, e-mail: [email protected]

Keywords: miR-424, miR-27a, PLAG1, TRAIL resistance, acute myeloid leukemia

Received: November 24, 2015     Accepted: March 07, 2016     Published: March 22, 2016


Although microRNAs have been elaborated to participate in various physiological and pathological processes, their functions in TRAIL resistance of acute myeloid leukemia (AML) remain obscure. In this study, we detected relatively lower expression levels of miR-424&27a in TRAIL-resistant and semi-resistant AML cell lines as well as newly diagnosed patient samples. Overexpression of miR-424&27a, by targeting the 3′UTR of PLAG1, enhanced TRAIL sensitivity in AML cells. Correspondingly, knockdown of PLAG1 sensitized AML cells to TRAIL-induced apoptosis and proliferation inhibition. We further found that PLAG1 as a transcription factor could reinforce Bcl2 promoter activity, causing its upregulation at the mRNA level. Both downregulated PLAG1 and elevated expression of miR-424&27a led to Bcl2 downregulation and augmented cleavage of Caspase8, Caspase3 and PARP in the presence of TRAIL. Restoration of Bcl2 could eliminate their effects on AML TRAIL sensitization. Overall, we propose that miR-424&27a and/or PLAG1 might serve as novel therapeutic targets in AML TRAIL therapy.

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