Long Non-Coding RNA LINC00152 Regulates Self-Renewal of Leukemia Stem Cells and Induces Chemo-Resistance in Acute Myeloid Leukemia

Abstract

Relapse of acute myeloid leukemia (AML) has a very poor prognosis and remains a common cause of treatment failure in patients with this disease. AML relapse is partially driven by the chemoresistant nature of leukemia stem cells (LSCs), which remains poorly understood, and our study aimed at elucidating the underlying mechanism. Accumulating evidences show that long noncoding RNAs (lncRNAs) play a crucial role in AML development. Herein, the lncRNA, LINC00152, was identified to be highly expressed in CD34+ LSCs and found to regulate the self-renewal of LSCs derived from AML patients. Importantly, LINC00152 upregulation was correlated with the expression of 16 genes within a 17-gene LSC biomarker panel, which contributed to the accurate prediction of initial therapy resistance in AML. Knockdown of LINC00152 markedly increased the drug sensitivity of leukemia cells. Furthermore, LINC00152 expression was found to be correlated with poly (ADP-ribose) polymerase 1 (PARP1) expression in AML, whereas LINC00152 knockdown significantly decreased the expression of PARP1. Upregulation of LINC00152 or PARP1 was associated with poor prognosis in AML patients. Collectively, these data highlight the importance and contribution of LINC00152 in the regulation of self-renewal and chemoresistance of LSCs in AML.

Long non-coding RNA LINC00152 in cancer: Roles, mechanisms, and chemotherapy and radiotherapy resistance

“…The inhibition of LINC00152 increased the sensitivity of leukemic cells to doxorubicin. These results suggest that LINC00152 may serve as a potential prognostic marker in AML patients ( 8 ). Transcriptome analysis has identified LINC00152 as a biomarker for early relapse and mortality in acute lymphoblastic leukemia ( 9 )…”

“…Cui et al ( 8 ) demonstrated that LINC00152 promotes PARP1 expression, which induces chemoresistance in acute myeloid leukemia and regulates the self-renewal of LSCs ( 8 ). In addition, knockdown of LINC00152 can inhibit PARP1 expression to improve the sensitivity of leukemia cells to chemotherapy, thus improving the prognosis of leukemia patients.…”

Diverse functions of long noncoding RNAs in acute myeloid leukemia: emerging roles in pathophysiology, prognosis, and treatment resistance

“…Moreover, the expression of LINC00152 was correlated with poly (ADP-ribose) polymerase 1 ( PARP1 ) expression and knockdown of LINC00152 resulted in decreased PARP1 expression which consequently resulted in an increased sensitivity of AML cells to the DNA damaging agent-doxorubicin. Thus, LINC00152 potentially contributes to the chemoresistance of LSCs in AML via upregulating PARP1 [56 ▪ ].…”

Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia

“…Previous studies have revealed that lncRNAs play essential roles in many important regulatory processes, such as transcription regulation, genome imprinting, chromatin modification, and nuclear transport, which have attracted widespread attention ( Groff et al, 2016 ; Long et al, 2017 ). Some lncRNAs, including CASC15 ( Fernando et al, 2017 ), UCA1 ( Li et al, 2020 ), H19 ( Zhang et al, 2018 ), HOTAIRM1 ( Chen et al, 2020 ), LINC00152 ( Cui et al, 2021 ), have been identified to be associated with the recurring mutations, clinical features and prognosis of AML. Accumulating studies have indicated that aberrant expression of certain specific lncRNAs in tumor cells can be used as a diagnostic marker or a potential drug target.…”