Abstract
BackgroundChronic myeloid leukemia (CML) is an acquired hematopoietic stem malignant disease originating from the myeloid system. Long non-coding RNAs (lncRNAs) have been widely explored in cancer tumorigenesis. However, their roles in CML remain largely unclear.MethodsThe peripheral blood mononuclear cells (PBMCs) and CML cell lines (K562, KCL22, MEG01, BV173) were collected for in vitro research. Real-time quantitative polymerase chain reaction was used to determine the mRNA expression levels. Cell viability and apoptosis were analyzed by cell counting kit 8 and flow cytometry assays. The targeting relationships were predicted using Starbase and TargetScan and ulteriorly verified by RNA pull-down and luciferase reporter assays. Western blotting assay was performed to assess the protein expressions. N6-methyladenosine (m6A) modification sites were predicted by SRAMP and confirmed by Methylated RNA immunoprecipitation (MeRIP) assay.ResultsLncRNA nuclear-enriched abundant transcript 1 (NEAT1) expression levels were decreased in the CML cell lines and PBMCs of CML patients. Moreover, METTL3-mediated m6A modification induced the aberrant expression of NEAT1 in CML. Overexpression of NEAT1 inhibited cell viability and promoted the apoptosis of CML cells. Additionally, miR-766-5p was upregulated in CML PBMCs and abrogated the effects of NEAT1 on cell viability and apoptosis of the CML cells. Further, CDKN1A was proved to be the target gene of miR-766-5p and was downregulated in the CML PBMCs. Knockdown of CDKN1A reversed the effects of NEAT1.ConclusionThe current research elucidates a novel METTL3/NEAT1/miR-766-5p/CDKN1A axis which plays a critical role in the progression of CML.
Highlights
Chronic myelocytic leukemia (CML) is a malignant clonal proliferative disease that manifests with a large number of immature white blood cells accumulating in the bone marrow, which inhibits the normal hematopoiesis of the bone marrow [1]
LncRNA nuclear-enriched abundant transcript 1 (NEAT1) expression levels were decreased in the CML cell lines and peripheral blood mononuclear cells (PBMCs) of CML patients
MiR-766-5p was upregulated in CML PBMCs and abrogated the effects of nuclear enriched abundant transcript 1 (NEAT1) on cell viability and apoptosis of the CML cells
Summary
Chronic myelocytic leukemia (CML) is a malignant clonal proliferative disease that manifests with a large number of immature white blood cells accumulating in the bone marrow, which inhibits the normal hematopoiesis of the bone marrow [1]. CML patients often suffer a characteristic reciprocal translocation t(9:22) (q34:q11) (Philadelphia chromosome) between chromosomes 9 and 22, forming a bcr-abl fusion gene, which aberrant expresses BCR-ABL protein with continuous tyrosine kinase activity [2]. BCR-ABL activates downstream signal transduction pathways, thereby regulates the expression of cytokines, further leading to immature myeloid cells release into the peripheral blood, that is, occurrence of CML [3]. Long non-coding RNAs (lncRNAs) have been widely explored in cancer tumorigenesis. Their roles in CML remain largely unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
