MYC upregulated LINC00319 promotes human acute myeloid leukemia (AML) cells growth through stabilizing SIRT6.

Abstract Long non-coding RNAs (lncRNAs) have been identified by accumulating studies as critical regulator in tumorigenesis and tumor development in human cancers, including in acute myeloid leukemia (AML). This study investigated the function and the underlying mechanism of LINC00319 in AML progression. Firstly, the low expression level of LINC00319 in whole blood of healthy individuals was obtained from UCSC, and its upregulation was detected in AML patients as well as AML cell lines. Besides, the prognostic significance of LINC00319 was revealed in AML patients. Functionally, the loss-of-function assays revealed that LINC00319 silence restrained proliferation but stimulated apoptosis in AML cells. Furthermore, LINC00319 expression was demonstrated proportional to MYC level in AML samples and transcriptionally regulated by MYC. Mechanistically, we identified FUS as a shared RNA binding protein (RBP) interacting with both LINC00319 and SIRT6. And LINC00319 regulated SIRT6 expression at post-transcriptional level through FUS-dependent pathway. Last but not least, SIRT6 overexpression rescued the suppressive effect of LINC00319 knockdown on AML cells growth. Overall, our findings unveiled that LINC00319 contributed to AML leukemogenesis via elevating SIRT6 expression, indicating a possible molecular target of LINC00319 for AML treatment. Graphical abstract Image 1 Highlights • Silencing LINC00319 that was upregulated in AML repressed cell proliferation but enhanced apoptosis in AML cells. • MYC was highly expressed in AML and upregulated LINC00319 expression transcriptionally in AML cells. • LINC00319 stabilized SIRT6 mRNA in AML through a FUS-dependent pathway. • The promotion effect of LINC00319 on the growth of AML cells was mediated by SIRT6. [ABSTRACT FROM AUTHOR]