lncRNA RAET1K Promotes the Progression of Acute Myeloid Leukemia by Targeting miR-503-5p/INPP4B Axis
Authors Li L, Wan D, Li L, Qin Y, Ma W
Received 9 November 2020
Accepted for publication 27 November 2020
Published 18 January 2021 Volume 2021:14 Pages 531—544
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Alberto Bongiovanni
Li Li,1 Dingming Wan,1 Lin Li,2 Yang Qin,1 Wang Ma3
1Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450052, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450052, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450052, People’s Republic of China
Correspondence: Wang Ma
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou City, Henan Province 450052, People’s Republic of China
Background: Although long non-coding RNA (lncRNA) RAET1K has been observed to be abnormally expressed in patients with various cancers, its role and molecular mechanism in acute myeloid leukemia (AML) remain unclear.
Methods: The expression of RAET1K and miR-503-5p in bone marrow tissues and cell lines was detected by qRT-PCR. Cell proliferation was evaluated by cell counting kit-8 and 5-ethynyl-20-deoxyuridine (EdU) staining assay. Cell invasion and migration were detected by transwell assay. Cell apoptosis was evaluated by flow cytometry. The relationship between RAET1K and miR-503-5p, as well as miR-503-5p and INPP4B, was determined by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In addition, the tumorigenesis of leukemia cells was evaluated by using a xenograft mouse model in vivo.
Results: RAET1K was significantly upregulated and miR-503-5p was markedly downregulated in bone marrow tissues and cell lines (HL-60 and THP-1). Silencing of RAET1K (si-RAET1K) and overexpression of miR-503-5p inhibited cell proliferation, migration, and invasion but promoted apoptosis of HL-60 and THP-1 cells. RAET1K functioned as a sponge of miR-503-5p, and miR-503-5p inhibitor obviously attenuated the effect of si-RAET1K on AML progression in vitro. INPP4B was identified as a target of miR-503-5p, and INPP4B overexpression obviously reversed the effect of miR-503-5p mimics on cell proliferation, migration, invasion, and apoptosis of HL-60 and THP-1 cells in vitro. Knockdown of RAET1K effectively inhibited the tumorigenesis of leukemia cells in vivo.
Conclusion: Our results demonstrated that RAET1K/miR-503-5p/INPP4B axis contributed to AML progression, suggesting that RAET1K might be a potential target for the treatment of AML.
Keywords: acute myeloid leukemia, RAET1K, miR-503-5p, INPP4B, tumorigenesis
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