Tumor suppressor miR-139-5p targets Tspan3 and regulates the progression of acute myeloid leukemia through the PI3K/Akt pathway.

Abstract

Dysregulation of microRNAs is closely implicated in the initiation and progression of human cancers including acute myeloid leukemia (AML). Though miR-139-5p was reported to be a potent tumor suppressor in adult AML, its underlying molecular mechanism in AML remains to be further defined. Herein, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were conducted to determine the expressions of miR-139-5p and tetraspanin3 (Tspan3) in AML patients and cells. Luciferase reporter assay, qRT-PCR, and Western blot analysis were carried out to detect the interaction between miR-139-5p and Tspan3. Cell proliferation, cell cycle distribution, invasion, and migration were evaluated by cell counting kit-8, flow cytometry, transwell invasion, and migration assays, respectively. Western blot analysis was conducted to determine phosphorylated-protein kinase B (Akt) and Akt levels. We found that a significant reduction in miR-139-5p expression and a prominent increase in Tspan3 expression were observed in AML patients and cells. Tspan3 was confirmed as a direct target of miR-139-5p and was negatively modulated by miR-139-5p. Rescue experiments showed that overexpression of miR-139-5p constrained cell proliferation, invasion and migration capabilities, and induced cell cycle arrest at the S phase in AML cells, which were partially reversed by Tspan3 overexpression. In addition, we found that miR-139-5p suppressed the phosphoinositide 3-kinase (PI3K)/Akt pathway in AML cells by targeting Tspan3. In conclusion, our study concluded that miR-139-5p suppressed the leukemogenesis in AML cells by targeting Tspan3 through inactivation of the PI3K/Akt pathway, providing a better understanding of AML progression.

• Authors: Ronghui Zhang, Ping Tang, Fang Wang, Ying Xing, Zhongxing Jiang, Shaoqian Chen, Xiaoli Meng, Linxiang Liu, Weijie Cao, Huayan Zhao, Ping Ma, Yanli Chen, Chao An, Ling Sun
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 120 Issue 3 Pg. 4423-4432 (03 2019) ISSN: 1097-4644 [Electronic] United States
• PMID: 30367526 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• MIRN139 microRNA, human
• MicroRNAs
• RNA, Neoplasm
• Tetraspanins
• Tspan3 protein, human
• Proto-Oncogene Proteins c-akt

Topics

• Cell Proliferation
• Genes, Tumor Suppressor
• HL-60 Cells
• Humans
• Leukemia, Myeloid, Acute (genetics, metabolism, pathology)
• MicroRNAs (genetics, metabolism)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• RNA, Neoplasm (genetics, metabolism)
• Signal Transduction
• THP-1 Cells
• Tetraspanins (genetics, metabolism)
• U937 Cells