LncRNA NR-104098 Inhibits AML Proliferation and Induces Differentiation Through Repressing EZH2 Transcription by Interacting With E2F1

Feng, Yongzeng; Hu, Shuang; Li, Lanlan; Zhang, Shengpeng; Liu, Jikang; Xu, Xiaoling; Zhang, Meiju; Du, Tian-Xi; Du, Yan; Peng, Xiaoqing; Chen, Feihu

doi:10.3389/fcell.2020.00142

Cited by 28 publications

(43 citation statements)

References 54 publications

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“…Our recent results show that ATPR can upregulate the expression of lncRNA NR-104098 and inhibit the differentiation and proliferation of AML induced by ATPR [11]. More in-depth mechanism studies showed that lncRNA NR-104098 played a role by enhancing the binding of E2F1 to EZH2 promoter [11]. Our results indicate that HOXA-AS2 can directly bind to EZH2 and inhibit the proliferation and induce differentiation of AML by regulating the expression of LATS2.…”

Section: Discussionmentioning

confidence: 58%

“…There are many reports that lncRNA can bind to EZH2, and then regulate the expression of downstream genes to exert its biological functions [5,33]. Our recent results show that ATPR can upregulate the expression of lncRNA NR-104098 and inhibit the differentiation and proliferation of AML induced by ATPR [11]. More in-depth mechanism studies showed that lncRNA NR-104098 played a role by enhancing the binding of E2F1 to EZH2 promoter [11].…”

Section: Discussionmentioning

confidence: 65%

“…With the continuous improvement and progress of experimental technology, more and more new lncRNAs have been discovered by RNA sequencing technology, which play a main role in the occurrence and development of diseases and malignant progress [2,25,37]. Many studies have shown that many lncRNAs express differently in AML and can regulate their functions [11,12,21,30]. However, the function and molecular mechanism of many lncRNAs associated with AML are still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…For the detection methods of differentiation indicators (CD11b and CD14), please refer to our previously published articles [11].…”

Section: Differentiation Marker Analysismentioning

confidence: 99%

“…Fluorescence in situ hybridization (FISH) was used to detect the location of HOXA-AS2 in the cells. The experimental method was similar to that reported before [11]. Fluorescence imaging was analyzed by laser scanning confocal microscope.…”

Section: Fluorescence In Situ Hybridization ( Sh)mentioning

confidence: 99%

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Long Noncoding RNA HOXA-AS2 Functions as an Oncogene by Binding to EZH2 and Suppressing LATS2 in AML

Feng

et al. 2020

Preprint

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BackgroundLong noncoding RNAs (lncRNAs) plays an important role in the development of physiology and pathology. Many reports have shown that LncRNA HOXA cluster antisense RNA 2 (HOXA-AS2) is a carcinogen and plays an important role in many tumors, but there are few reports on its role in Acute myeloid leukemia (AML). MethodsThe expression of HOXA-AS2 in AML cell line was detected by qRT-PCR. AML cases from the public database (GEPIA) were also included in this study. Cell counting kit-8 (CCK-8) assay, flow cytometry, immunofluorescence and Western blot were used to detect the role of HOXA-AS2 in AML cells. Luciferase reporter gene detection, RIP, RNA pull-down and RNA-ChIP detection were used to demonstrate the molecular biological mechanism of HOXA-AS2 in AML.ResultsOur results show that HOXA-AS2 was upregulated in AML cell lines and tissues, and the overexpression of HOXA-AS2 is negatively correlated with the survival of patients. Silencing HOXA-AS2 can inhibit the proliferation and induce differentiation of AML cells in vitro and in vivo. After overexpressing HOXA-AS2, it will show the opposite result. Moreover, more in-depth mechanism studies show that HOXA-AS2 exerts its carcinogenicity mainly by binding with the epigenetic inhibitor Enhancer of zeste homolog 2 (EZH2) and then inhibiting the expression of Large Tumor Suppressor 2 (LATS2). ConclusionsTaken together, our results highlight the important role of HOXA-AS2 in AML, suggesting that HOXA-AS2 may be an effective therapeutic target for patients with AML.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

“…For the detection methods of differentiation indicators (CD11b and CD14), please refer to our previously published articles [11].…”

Section: Differentiation Marker Analysismentioning

confidence: 99%

Section: Fluorescence In Situ Hybridization ( Sh)mentioning

confidence: 99%

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Long Noncoding RNA HOXA-AS2 Functions as an Oncogene by Binding to EZH2 and Suppressing LATS2 in AML

Feng

et al. 2020

Preprint

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Long noncoding RNAs: A novel insight in the leukemogenesis and drug resistance in acute myeloid leukemia

Kirtonia

Ashrafizadeh

Zarrabi

et al. 2021

Journal Cellular Physiology

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Acute myeloid leukemia (AML) is a common hematological disorder with heterogeneous nature that resulted from blocked myeloid differentiation and an enhanced number of immature myeloid progenitors. During several decades, different factors, including cytogenetic, genetic, and epigenetic have been reported to contribute to the pathogenesis of AML by inhibiting the differentiation and ensuring the proliferation of myeloid blast cells. Recently, long noncoding RNAs (lncRNAs) have been considered as potential diagnostic, therapeutic, and prognostic factors in different human malignancies including AML. Altered expression of lncRNAs is correlated with the transformation of hematopoietic stem and progenitor cells into leukemic blast cells because of their distinct role in the key cellular processes. We discuss the significant role of lncRNAs in the proliferation, survival, differentiation, leukemic stem cells in AML and their involvement in different molecular pathways (insulin-like growth factor type I receptor, FLT3, c-KIT, Wnt, phosphatidylinositol 3-kinase/ protein kinase-B, microRNAs), and associated mechanisms such as autophagy, apoptosis, and glucose metabolism. In addition, we aim to highlight the role of lncRNAs as reliable biomarkers for diagnosis, prognosis, and drug resistance for precision medicine in AML.

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The tip of the iceberg—The roles of long noncoding RNAs in acute myeloid leukemia

Connerty

Lock

2023

WIREs RNA

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Long noncoding RNAs (lncRNAs) are traditionally defined as RNA transcripts longer than 200 nucleotides that have no protein coding potential. LncRNAs have been identified to be dysregulated in various types of cancer, including the deadly hematopoietic cancer—acute myeloid leukemia (AML). Currently, survival rates for AML have reached a plateau necessitating new therapeutic targets and biomarkers to improve treatment options and survival from the disease. Therefore, the identification of lncRNAs as novel biomarkers and therapeutic targets for AML has major benefits. In this review, we assess the key studies which have recently identified lncRNAs as important molecules in AML and summarize the current knowledge of lncRNAs in AML. We delve into examples of the specific roles of lncRNA action in AML such as driving proliferation, differentiation block and therapy resistance as well as their function as tumor suppressors and utility as biomarkers.This article is categorized under: RNA in Disease and Development > RNA in Disease

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LncRNA NR-104098 Inhibits AML Proliferation and Induces Differentiation Through Repressing EZH2 Transcription by Interacting With E2F1

Cited by 28 publications

References 54 publications

Long Noncoding RNA HOXA-AS2 Functions as an Oncogene by Binding to EZH2 and Suppressing LATS2 in AML

Long Noncoding RNA HOXA-AS2 Functions as an Oncogene by Binding to EZH2 and Suppressing LATS2 in AML

Long noncoding RNAs: A novel insight in the leukemogenesis and drug resistance in acute myeloid leukemia

The tip of the iceberg—The roles of long noncoding RNAs in acute myeloid leukemia

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