LncRNA ANRIL regulates AML development through modulating the glucose metabolism pathway of AdipoR1/AMPK/SIRT1

Abstract

The long noncoding RNA ANRIL has been found to be abnormally expressed and play important roles in different cancers. However, the expression and function of ANRIL in acute myeloid leukemia (AML) remain to be declared. In this study, we found that ANRIL is up-regulated in AML patients at diagnosis and down-regulated in patients after complete remission (CR). Functional studies showed that knockdown of ANRIL expression resulted in a decline in glucose uptake and inhibition of AML cell maintenance in vitro and in vivo. Mechanically, ANRIL was found to repress the expression of Adiponectin receptor (AdipoR1), a key regulator of glucose metabolism. Both ANRIL and AdipoR1 knockdown reduced the expression levels of phosphorylation of AMPK and SIRT1, implying a previously unappreciated ANRIL-AdipoR1-AMPK/SIRT1 signaling pathway in regulating cell glucose metabolism and survival in AML. The study is the first to demonstrate that ANRIL promotes malignant cell survival and cell glucose metabolism to accelerate AML progression and is a potential prognostic marker and therapeutic target in AML treatment.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0879-9) contains supplementary material, which is available to authorized users.

The implication of lncRNA expression pattern and potential function of lncRNA RP4‐576H24.2 in acute myeloid leukemia

“…For instance, knockdown of lncRNA ZFAS1 represses the AML progression through mediating the miR‐150/Sp1 and miR‐150/Myb pathways . And lncRNA ANRIL enhances the malignant cell survival and cell glucose metabolism of AML by regulating the AdipoR1/AMPK/SIRT1 pathway . In addition, lncRNA UCA1 expression is increased in AML pediatric patients after adriamycin (ADR)‐based chemotherapy, and knockdown of lncRNA UCA1 inhibits chemoresistance to ADR in AML cells via mediating miR‐125a/hexokinase 2 pathway .…”

“…Previous studies reveal that some specific lncRNAs might play crucial roles in regulating the AML cell functions or chemoresistance, for instance, a previous study reports that lncRNA urothelial carcinoma‐associated 1 (UCA1) knockdown inhibits chemoresistance via repressing glycolysis by mediating the microRNA (miR)‐125a/hexokinase 2 signaling pathway . However, the existed studies mostly focus on investigating the roles of several specific/individual lncRNAs in AML, such as lncRNA antisense noncoding RNA in the INK4 locus (ANRIL), lncRNA UCA1 and so on, while the studies assessing the lncRNA expression pattern in AML are few …”

“…11,12 However, the existed studies mostly focus on investigating the roles of several specific/individual lncRNAs in AML, such as lncRNA antisense noncoding RNA in the INK4 locus (ANRIL), lncRNA UCA1 and so on, while the studies assessing the lncRNA expression pattern in AML are few. 11,13 Herein, we conducted this study to investigate the implication of lncRNA expression pattern in AML pathogenesis and the potential of several specific candidate lncRNAs as markers for AML risk and prognosis, and further explore the effect of lncRNA RP4-576H24.2 on regulating AML progression.…”

“…33 And lncRNA ANRIL enhances the malignant cell survival and cell glucose metabolism of AML by regulating the AdipoR1/AMPK/SIRT1 pathway. 13 In addition, lncRNA UCA1 expression is increased in AML pediatric patients after adriamycin (ADR)-based chemotherapy, and knockdown of lncRNA UCA1 inhibits chemoresistance to ADR in AML cells via mediating miR-125a/hexokinase 2 pathway. 11 And lncRNA TUG1 suppresses AML cell proliferation while promotes apoptosis through targeting aurora kinase A.…”

The Advancement of Long Non-Coding RNAs in Cholangiocarcinoma Development

“…LncRNA may affect pathophysiological metabolism of CCA [60]. It is well known that abnormal glutamine is characteristic in tumor tissues and related to tumorigenesis and development [61].…”