<p>CircRAD18 Accelerates the Progression of Acute Myeloid Leukemia by Modulation of miR-206/PRKACB Axis</p>

Abstract

Background Circular RNAs (circRNAs) play a crucial role in tumorigenesis. However, the effects of circRNAs on acute myeloid leukemia (AML) remain largely unexplored. We explored the function of circRAD18 in AML development. Methods QRT-PCR was performed for the levels of circRAD18, RAD18, microRNA-206 (miR-206) and protein kinase CAMP-activated catalytic subunit beta ( PRKACB ). Cell Counting Kit-8 (CCK-8) assay and colony formation assay were utilized for cell proliferation. Flow cytometry analysis was carried out to analyze cell apoptosis and cell cycle process. Transwell assay was manipulated for cell migration and invasion. Western blot assay was conducted for protein levels. Dual-luciferase reporter assay was adopted to verify the interaction between miR-206 and circRAD18 or PRKACB . Results CircRAD18 level was increased in AML patients’ blood specimens and AML cell lines compared to normal controls. CircRAD18 knockdown impeded the proliferation, migration and invasion and facilitated the apoptosis and cell cycle arrest in AML cells. Moreover, circRAD18 was identified as a sponge for miR-206, and circRAD18 knockdown-mediated effect on AML cell progression was reversed by miR-206 suppression. Additionally, PRKACB was the target gene of miR-206. MiR-206 overexpression suppressed the malignant behaviors of AML cells, while PRKACB elevation restored the effects. Conclusion CircRAD18 aggravated the malignancy of AML cells through reducing miR-206 expression and elevating PRKACB expression, indicating circRAD18 might be a therapeutic target for AML.

Downregulation of circ_0012152 inhibits proliferation and induces apoptosis in acute myeloid leukemia cells through the miR‐625‐5p/SOX12 axis

“…Likewise, many circRNAs have been verified to play a key part in the tumorigenesis of AML through serving as tumor suppressors 9,10 . For instance, circRAD18 facilitated AML progression through modulating miR‐206/PRKACB pathway 27 . Moreover, circ_0012152, derived from RNF220, was demonstrated to be highly expressed in AML tissues relative to normal tissues, 12 but its special molecular mechanism in AML remains largely elusive.…”

“…9,10 For instance, circRAD18 facilitated AML progression through modulating miR-206/PRKACB pathway. 27 Moreover, circ_0012152, derived from RNF220, was demonstrated to be highly expressed in AML tissues relative to normal tissues, 12 but its special molecular mechanism in AML remains largely elusive. Consistent with above research, in this study, circ_0012152 was found to be upregulated in AML, and high circ_0012152 expression was closely related to overall survival.…”

Advances in the Study of circRNAs in Hematological Malignancies

“…AML is a disease caused by malignant proliferation of myeloid cells in the bone marrow ( 45 ).Acute myelogenous leukemia (AML) is the most prevalent acute leukemia in adults ( 66 ). Although the diagnosis and treatment strategies of AML have been rapidly developed, the prognosis remains poor ( 44 ). With the advancement of analytical techniques, many circRNAs have been identified to be abnormally expressed in AML.…”

“…Furthermore, circ-vimentin overexpression is considered an independent and poor prognostic factor for significantly shorter overall survival (OS) and leukemia-free survival (LFS) in patients with AML ( 43 ). circ-RAD18 was found to be highly expressed in patients with AML, promotes AML cell proliferation, and accelerates tumor progression via miR-206/ protein kinase CAMP-activated catalytic subunit beta (PRKACB) ( 44 ). PRKACB participates in various biological processes, including cell replication, gene transcription, and metabolism ( 44 , 67 ).…”

Circular RNA hsa_circ_0016863 Regulates the Proliferation, Migration, Invasion and Apoptosis of Hepatocellular Carcinoma

“…In acute myeloid leukemia (AML), circRAD18 acts as a sponge for miR-206, while PRKACB is a miR-206 downstream target gene. In AML, upregulated circRAD18 promotes AML progression by decreasing miR-206 and elevating PRKACB, providing a reference direction for the treatment of AML [26]. NOTCH1 has been implicated in the progression of multiple tumors.…”