2. Academic Validation
  3. Circular RNA PVT1 regulates cell proliferation, migration and apoptosis by stabilizing c-Myc and its downstream target CXCR4 expression in acute myeloid leukemia

Circular RNA PVT1 regulates cell proliferation, migration and apoptosis by stabilizing c-Myc and its downstream target CXCR4 expression in acute myeloid leukemia

  • Turk J Haematol. 2023 Jan 31. doi: 10.4274/tjh.galenos.2023.2022.0435.
Xian-Fu Sheng 1,  Li-Li Hong 1,  Lei Fan 2,  Yu Zhang 1,  Kai-Li Chen 1,  Jie Mu 1,  Si-Yu Shen 1,  Hai-Feng Zhuang 1
Affiliations

Affiliations

  • 1 The department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang Province, People's Republic of China.
  • 2 Department of pharmacy,The Second Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou,Zhejiang Province, People's Republic of China.
PMID: 36718632 DOI: 10.4274/tjh.galenos.2023.2022.0435
Abstract

Objective: This study aimed to investigate the role and mechanism of circular RNA PVT1 (circPVT1) in patients with acute myeloid leukemia (AML).

Materials and methods: The expression of circPVT1 in 23 de novo AML (not acute promyelocytic leukemia, not APL) patients and cell lines were detected by RT-qPCR. Loss of function assays were carried out to explore the influence of silenced circPVT1 on the proliferation, migration, and Apoptosis in THP-1 cell line. CCK-8 assays, Transwell assays and Annexin V/PI staining assays were performed to assess the proliferation, migration and Apoptosis, respectively.

Results: CircPVT1 was highly expressed in AML patients and myeloid cell lines compared with healthy controls. Higher expression of circPVT1 was related to shorter overall survival (OS) and relapse-free survival (RFS) in AML patients. Cell viability and migration were inhibited, and Apoptosis was increased when circPVT1 was knockdown in THP-1 cells. Knockdown of circPVT1 resulted in markedly suppression of c-Myc protein, with no significant change in mRNA level. We also found that circPVT1 knockdown markedly increased the phosphorylation of c-Myc Thr-58, which was responsible for c-Myc degradation. Silencing of c-Myc caused a significant decrease in the CXCR4 mRNA and protein expression, whereas the overexpression of c-Myc caused the opposite result, suggesting that CXCR4 is a target molecule of c-Myc. Lastly, we found that overexpression of c-Myc could partially reverse circPVT1 knockdown-induced anti-tumour effects on THP-1 cells in vitro.

Conclusion: Our results showed that circPVT1 was highly expressed in AML patients and was related to shorter OS and RFS. CircPVT1 may exert an oncogenic role in THP-1 cells by stabilizing c-Myc protein expression and its downstream target CXCR4 expression. These data indicated that circPVT1 may be a promising therapeutic target for AML.

Keywords

Acute myeloid leukemia; CXCR4; c-Myc; circPVT1.

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