LINC00504 promotes the progression of acute myeloid leukemia by targeting MDM2.

Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignant tumor, accompanied by the abnormal cloning of myeloid hematopoietic stem cells, little is known about its etiological role and pathogenesis. We aimed to explore the effect and regulatory mechanism of LINC00504 on the malignant phenotypes of AML cells. In this study, LINC00504 levels in AML tissues or cells were ascertained by PCR. RNA pull-down and RIP assays were conducted to verify the combination of LINC00504 and MDM2. Cell proliferation was detected by CCK-8 and BrdU assays, apoptosis was checked by flow cytometry, and glycolytic metabolism levels were detected by ELISA analysis. The expressions of MDM2, Ki-67, HK2, cleaved caspase-3, and p53 were detected by western blotting and immunohistochemistry. A xenograft tumor model was used to detect the role of LINC00504 in vivo. Results showed that LINC00504 was highly expressed in AML and its high expression was related to clinicopathological features in AML patients. LINC00504 knockdown significantly inhibited the proliferation and glycolysis, while inducing apoptosis of AML cells. Meanwhile, LINC00504 downregulation also exerted a significant alleviating effect on AML cell growth in vivo. In addition, LINC00504 could bind to MDM2 protein and positively regulate its expression. Overexpression of LINC00504 promoted the malignant phenotypes of AML cells and partially reversed the inhibitory effects of LINC00504 knockdown on AML progression. In conclusion, LINC00504 facilitated AML cell proliferation and suppressed apoptosis through upregulating MDM2 expression, suggesting that LINC00504 may serve as a prognostic marker and therapeutic target in patients with AML.