J Cancer 2020; 11(23):7081-7090. doi:10.7150/jca.47294 This issue

Research Paper

Long non-coding RNA GHET1/miR-105/RAP2B axis regulates the progression of acute myeloid leukemia

Yue Xiao, Tangfei Li, Qianfu Xue, Lili Miao

Yongchuan Hospital of Chongqing Medical University, Yongchuan, Chongqing, China.

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Citation:
Xiao Y, Li T, Xue Q, Miao L. Long non-coding RNA GHET1/miR-105/RAP2B axis regulates the progression of acute myeloid leukemia. J Cancer 2020; 11(23):7081-7090. doi:10.7150/jca.47294. Available from https://www.jcancer.org/v11p7081.htm

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Abstract

Background: To explore the biological effects and potential molecular mechanisms of long non-coding RNA (lncRNA) gastric carcinoma proliferation enhancing transcript 1 (GHET1) in acute myeloid leukemia (AML).

Methods: Fluorescence in situ hybridization was performed to determine the location of GHET1. Quantitative polymerase chain reaction (qPCR) was performed to verify RNA expression. GHET1 overexpression and knockdown were achieved by transfection of the expression vector or short hairpin RNA. Western blotting, qPCR, Cell Counting Kit-8 assay, JC-1 staining, and flow cytometry were performed to measure GHET1 function. The dual luciferase reporter assay was performed to confirm the relationship between microRNA 105 (mir-105) and Ras-related protein Rap-2B (RAP2B).

Results: GHET1 was localized in the nucleus of NB4 cell lines. GHET1 expression was elevated in AML cell lines compared with normal bone marrow mononuclear cells. GHET1 knockdown led to inhibition of proliferation and promoted the differentiation and apoptosis of AML cell lines. Furthermore, GHET1 directly bound to miR-105 and downregulated miR-105 expression. MiR-105 overexpression suppressed proliferation and induced the differentiation and apoptosis of AML cell lines. In addition, RAP2B was confirmed to be a target gene of miR-105 and an inverse correlation was shown between their expression levels in AML cell lines; when miR-105 increased, Rap-2B level decreased and vice versa.

Conclusion: This study demonstrated that the GHET1/miR-105/Rap2B axis may be a critical signaling pathway involved in AML progression.

Keywords: lncRNA GHET1, acute myeloid leukemia, miR-105, RAP2B