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Downregulation of PDIA3 inhibits proliferation and invasion of human acute myeloid leukemia cells

Authors Ye Q, Fu P, Dou J, Wang N

Received 12 January 2018

Accepted for publication 24 February 2018

Published 17 May 2018 Volume 2018:11 Pages 2925—2935

DOI https://doi.org/10.2147/OTT.S162407

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Samir Farghaly


Qidong Ye,1 Pan Fu,2 Jiaying Dou,2 Nina Wang2

1Department of Pediatrics, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, People’s Republic of China; 2Department of Hematology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China

Introduction: Acute myeloid leukemia (AML) is a common malignancy of the hematopoietic system. In bone marrow samples of AML patients, PDIA3 expression was higher than that in the samples of healthy controls. We aimed at exploring the effect of PDIA3 siRNA on proliferation, apoptosis, migration, and invasion of AML HL-60 and HEL cells.
Materials and methods: RT-PCR was performed to identify PDIA3 expression. Cell proliferation was assessed by MTT. Flow cytometry analysis and transwell were used to detect cell apoptosis, migration and invasion. Gene set enrich-ment analysis (GSEA) was employed to explore the PDIA 3-associated pathways in AML. Western blotting was used for protein expression detection.
Results: PDIA3 siRNA significantly inhibited the proliferation of AML cells at 24 and 48 h. PDIA3 siRNA notably enhanced the percentage of apoptotic cells. The migration and invasion abilities of HL-60 and HEL cells in the PDIA3 siRNA group were significantly suppressed compared with those in the control and siNC groups. GSEA of the Cancer Genome Atlas dataset showed that Kyoto Encyclopedia of Genes and Genomes oxidative phosphorylation and amino sugar and nucleotide sugar metabolism pathways could be correlated with PDIA3 expression; this was further confirmed in AML cells by Western blotting. MAPK signaling was also blocked by PDIA3 siRNA.
Conclusion: PDIA3 siRNA effectively enhanced apoptosis, and suppressed proliferation, invasion, and migration of AML cells by regulating oxidative phosphorylation and amino sugar and nucleotide sugar metabolism pathways, and MAPK signaling, which can provide novel therapeutic targets for AML.

Keywords: PDIA3, acute myeloid leukemia, migration, invasion, gene set enrichment analysis, MAPK pathway
 

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