Abstract
Acute myeloid leukemia (AML) is a malignant tumor derived from leukemia stem cells, with complicated pathogenesis. LncRNAs play an important role in tumors genesis and progression. According to results from bioinformatics analysis, lncRNA USP30-AS1 is highly expressed in AML and both the high expression of USP30-AS1 and low methylation level at Cg03124318 locus of USP30-AS1 gene promoter are associated with poor prognosis of AML. This study knocked down and overexpressed USP30-AS1 to determine the roles in AML cell lines. High-throughput sequencing was performed to explore the genes regulated by USP30-AS1. Results showed that USP30-AS1 promoted AML cell viability and inhibited apoptosis. Genes regulated by USP30-AS1 are mainly related to genetic regulation and immune system. Among them, USP30 and ANKRD13A genes are close to USP30-AS1 gene in chromosome. Knockdown of USP30, but not ANKRD13A, abolished the cancer-promoting effects of USP30-AS1. ANKRD13A recognizes Lys-63-linked polyubiquitin chain in HLA-I. USP30-AS1 induced HLA-I internalization from the cell membrane by up-regulating ANKRD13A, which might induce the immune escape of AML cells. ChIP analysis revealed that the regulatory effects of USP30-AS1 on USP30 and ANKRD13A are associated with H3K4me3 and H3K27Ac. In summary, USP30-AS1 probably promotes AML cell survival by cis-regulating USP30 and ANKRD13A.
Highlights
Acute myeloid leukemia (AML) is a malignancy of bonemarrow hematopoietic stem/progenitor cells, including all non-lymphoid acute leukemias, and is the most common type of adult acute leukemia [1]
Survival analysis showed that high expression of USP30AS1 was associated with a lower overall survival rate (***p < 0.001, Fig. 1B), indicating that the high expression of USP30-AS1 was associated with the poor prognosis of AML
It can judge that the hypomethylation of Cg03124318 might lead to the high expression of USP30-AS1 in AML, whereby associating to poor prognosis
Summary
Acute myeloid leukemia (AML) is a malignancy of bonemarrow hematopoietic stem/progenitor cells, including all non-lymphoid acute leukemias, and is the most common type of adult acute leukemia [1]. It has rapid onset, rapid development and serious harm. The changes in the genome can lead to the disruption of the expression of oncogenes and tumor suppressor genes, promoting tumor formation [3]. Epigenetics is one of the key areas in the study of genomic function and regulation of gene expression. In a study of determining the key epigenetic genes in AML, Hu et al found that the hypomethylated ZNRF2 gene promotes
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
