Effects And Mechanisms And Of LncRNA-HOTAIR In AML Cell Differentiation Induced By ATRA

Background and objective: Acute myeloid leukemia is a hematological malignancy origin from myeloid hematopoietic stem cells,it may occur at any age with a rapid disease progress and poor prognosis.All-transretinoic acid has improved the treatment and prognosis of acute promyelocytic leukemia,the most dangerous kind of AML,a lot in recent years.However,treatment of the rest of AML remains poor,further mechanism research is wanted.Long non-coding RNA,longer than 200 bp in length,without the ability to translate into protein.Lnc RNA play an important role in numerous biological roles including epigenetic regulation,apoptosis,cell cycle and tumor progress.HOTAIR is a lnc RNA with 2158 bp in length,located in HOXC locus on chromosome 12.HOTAIR act as an oncogene through epigenetic regulation,promote cancer cell proliferation and differentiation in many tumors,but the function of HOTAIR in AML remains unknown.Here,we aims to investigated the role of HOTAIR during the AML cell differentiation induced by ATRA.Methods: The expression of HOTAIR was evaluated in bone marrow of 45 AML patients and 15 IDA patients,AML cell lines by q PCR.AML cell differentiation was induced by ATRA and the differentiation was estimate by FCM.Then,si RNA was used to investigate the function of HOTAIR,and western blot was used to detect the cell cycle protein.Furthermore,Kaplan-Meier was used to analyze the relationship between HOTAIR and prognosis of AML patients.Results: The expression of CD11 b and HOTAIR were upregulated by ATRA,and AML cell differentiation was decreased by knockdown HOTAIR.Furthermore,knockdown HOTAIR leads to cell cycle alter,that level of G0/G1 phase decrease and level of S phase increase.And CDK4 and cyclin D1 was upregulated,p21 wasdownregulated after knockdown of HOTAIR.In addition,HOTAIR was downregulated in AML-M2 patients and HOTAIR was correlated with WBC counts.Conclusion: 1.ATRA upregulated the expression of HOTAIR.2.HOTAIR participated in AML cell differentiation by regulated cell cycle;3.HOTAIR regulated expression of CDK4,cyclin D1 and p21 protein.4.HOTAIR correlated with WBC count in AML patients;5.HOTAIR may serve as a potential target in AML.