Silencing of lncRNA UCA1 curbs proliferation and accelerates apoptosis by repressing SIRT1 signals by targeting miR‐204 in pediatric AML

Abstract

The long noncoding RNA urothelial carcinoma‐associated 1 (UCA1) has been reported to sustain the proliferation of acute myeloid leukemia (AML) cells through downregulating cell cycle regulators p27kip1. Yet, the foundational mechanism of UCA1 in AML pathologies remains unclear. Herein, we found an escalation of UCA1 expression and suppression of miR‐204 expression in pediatric AML patients and cells. UCA1 silencing suppressed cell proliferative abilities, promoted apoptotic rates, decreased Ki67, and increased cleaved caspase‐3 in AML cells. Moreover, UCA1 sponged miR‐204 and suppressed its expression. UCA1 overexpression inversed the miR‐204 suppressed proliferation and promoted apoptosis. UCA1 also boosted the expression of SIRT1, a miR‐204 target, via the sponging interaction. Furthermore, miR‐204 inhibited inducible nitric oxide synthase and cyclooxygenase‐2 expression, while UCA1 overexpression inversed the inhibitory effects in AML cells. Our findings concluded that UCA1 downregulation repressed cell proliferation and promoted apoptosis through inactivating SIRT1 signals by upregulating miR‐204 in pediatric AML.

Identification of prognostic biomarkers and potential regulatory axes for acute myeloid leukemia based on a competitive endogenous RNA network

“…7a). Besides, several studies indicate that abnormal expression of lncRNAs is often associated with the development of AML [3,24]. Therefore, it is reasonable to suggest CTB-193M12.1 as a regulatory gene of AML.…”

Role of Nitric Oxide in Gene Expression Regulation during Cancer: Epigenetic Modifications and Non-Coding RNAs

“…The reduction in miR-204 has been related to UCA1 expression in acute myeloid leukemia (AML) cultured cells and in patients. The proapoptotic and antiproliferative properties of miR-204 were associated with the reduced expression of SIRT1, COX2 and NOS2 in AML cells [118] (Figure 3B2). In this setting, UCA1 exerted sponging interaction with miR-204 and prevented all downstream events in AML cells [118].…”

The Role of cis- and trans-Acting RNA Regulatory Elements in Leukemia

“…Downregulation of XLOC_109948 in a NPM1-mutated OCI-AML3 cell line treated with Ara-C or ATRA enhanced apoptosis, thus suggesting the role of this lncRNA in drug sensitivity [119]. lncRNAs contribute to proliferation [104,[120][121][122][123][124][125][126], chemoresistance [105,127], and shorter overall survival [128][129][130][131][132] in childhood leukemia, while functions of some highly upregulated and downregulated lncRNAs are still unknown [133], Table 2. Urothelial carcinoma-associated 1 (UCA1) lncRNA was upregulated in some pediatric AML after adriamycin (ADR)-based chemotherapy [105].…”