LncRNA UCA1 Promotes the Progression of AML by Upregulating the Expression of CXCR4 and CYP1B1 by Affecting the Stability of METTL14

Abstract

Objective. Increasing numbers of studies have proved that m6A methylation plays crucial roles in different cancers. However, how lncRNA regulates m6A methylation and participates in acute myeloid leukemia (AML) remains unclear. Therefore, this study aims to explore the function and mechanism of UCA1 in AML by regulating m6A methylation. Methods. qRT-PCR, western blot, and immunohistochemical staining were used to detect the expression of METTL14, CXCR4, and CYP1B1. qRT-PCR was used to detect the expression of UCA1. CCK8, flow cytometry, and transwell assays were used to detect the proliferation, apoptosis, migration, and invasion of HL60 and U937 cells, respectively. m6A methylation was detected by dot blot analysis. Tumor-bearing mice were established, and tumor weight and volume were analyzed. Immunofluorescence staining, co-localization, and RNA pull-down were used to confirm the reaction between UCA1 and METTL14. Results. Overexpression of UCA1 promotes AML development in vitro. Furthermore, we found that METTL14-influenced m6A methylation could be affected by UCA1. UCA1 promoted AML development by regulating m6A methylation. Moreover, the expression of CYP1B1 and CXCR4 was affected by METTL14. In addition, UCA1 promoted AML development by affecting m6A methylation in vivo. Conclusion. In the present study, we demonstrated that lncRNAUCA1 promotes the progression of AML by upregulating the expression of CXCR4 and CYP1B1 by affecting the stability of METTL14.

MicroRNA-1306-5p Regulates the METTL14-Guided m6A Methylation to Repress Acute Myeloid Leukemia

“…In addition, the relationship between METTL14 and AML is also reported in recent years. Li et al pointed that METTL14 could promote the progression of AML via combining with long noncoding RNA UCA1 [ 10 ]. However, there is few studies focusing on the regulatory mechanism of this effect.…”

Non-coding RNA and autophagy: Finding novel ways to improve the diagnostic management of bladder cancer

“…Mechanistically, UCA1 was shown to physically interact with EZH2, which blocked the p21 expression through histone methylation, and parallelly UCA1 expression mediates phosphorylation of CAMP responsive element binding protein (CREB) and PI3K/AKT and thereby facilitates tamoxifen-mediated resistance ( Fan et al, 2014b ). In addition, UCA1 has also been shown to mediate resistance during cisplatin treatment by Cytochrome P450 Family 1 Subfamily B Member 1 (CYP1B1)-mediated apoptosis via miR-513a-3 upregulation ( Li et al, 2022b ). UCA1 expression was shown to be positively related to CYP1B1 expression.…”

RNA Modifications Meet Tumors

“… 94 , 95 For example, lncRNA UCA1 can promote the progression of acute myeloid leukemia (AML) by increasing the expression of METTL14. 96 Furthermore, the level of m 6 A expression in follicular lymphoma and AML may be used to monitor the tumor microenvironment for targeted treatment. Similarly, detecting m 6 A modification levels in lncRNA helps evaluate the prognostic level of patients with acute and chronic myelogenous leukemia.…”