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      Long noncoding RNA NEAT1 modulates cell proliferation and apoptosis by regulating miR-23a-3p/SMC1A in acute myeloid leukemia : ZHAO et al.

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          Abstract

          The aim of this study was to determine the function of the NEAT1/miR-23a-3p/SMC1A axis in cell proliferation and apoptosis in acute myeloid leukemia (AML). Microarray analysis was used to screen differentially expressed lncRNAs/miRNAs/mRNAs in primary AML cells. The expression of nuclear paraspeckle assembly transcript 1 (NEAT1), miR-23a-3p, and structural maintenance of chromosome 1 alpha (SMC1A) in primary AML cells and THP-1 cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR). A Cell Counting Kit-8 (CCK-8) assay was used to analyze proliferation. Cell cycle progression and apoptosis were examined by flow cytometry. RNA immunoprecipitation (RIP) and dual-luciferase assays were performed to determine the correlation between miR-23a-3p and NEAT1 or SMC1A. The qRT-PCR illustrated that NEAT1 and SMC1A expression was decreased but that miR-23a-3p expression was increased in primary AML cells and THP-1 cells compared with that in normal cells. The RIP assay and dual-luciferase assay revealed the targeting relationship between miR-23a-3p and NEAT1 or SMC1A. The CCK-8 assay showed that the overexpression of NEAT1 and SMC1A or repression of miR-23a-3p inhibited cell proliferation. Flow cytometry showed that the upregulation of NEAT1 and SMC1A or repression of miR-23a-3p promoted apoptosis and affected the cell cycle. NEAT1 repressed the expression of miR-23a-3p, and therefore promoted SMC1A, which in turn suppressed myeloid leukemia cell proliferation and enhanced apoptosis.

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          Long non-coding RNA cox-2 prevents immune evasion and metastasis of hepatocellular carcinoma by altering M1/M2 macrophage polarization

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            Long Non-Coding RNA CCAT1 Acts as a Competing Endogenous RNA to Regulate Cell Growth and Differentiation in Acute Myeloid Leukemia

            Long non-coding RNAs (lncRNAs) are involved in multiple cellular events, as well as in tumorigenesis. Colon cancer-associated transcript-1 (CCAT1) gene encodes an lncRNA whose over-activation was observed in an expanding list of primary human solid tumors and tumor cell lines, however its biological roles in acute myeloid leukaemia (AML) has not been reported yet at present. In this study, the aberrant upregulation of CCAT1 was detected in French-American-British M4 and M5 subtypes of adult AML patients. By gain- and loss-of-function analysis, we determined that CCAT1 repressed monocytic differentiation and promoted cell growth of HL-60 by sequestering tumor suppressive miR-155. Accordingly, a significant decrease in miR-155 level was detected in AML patients. Re-introduction of miR-155 into HL-60 cells restored monocytic maturation and repressed cell proliferation. Furthermore, CCAT1 could up-regulated c-Myc via its competing endogenous RNA (ceRNA) activity on miR-155. In conclusion, these results revealed new mechanism of lncRNA CCAT1 in AML development, and suggested that the manipulation of CCAT1 expression could serve as a potential strategy in AML therapy.
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              Long non-coding RNA HOTAIR modulates c-KIT expression through sponging miR-193a in acute myeloid leukemia.

              HOTAIR is significantly overexpressed in various cancers and facilitates tumor invasion and metastasis. However, whether HOTAIR plays oncogenic roles in acute myeloid leukemia (AML) is still unknown. Here, we report that HOTAIR expression was obviously increased in leukemic cell lines and primary AML blasts. Clinically, AML patients with higher HOTAIR predicted worse clinical outcome compared with those with lower HOTAIR. Importantly, HOTAIR knockdown by small hairpin RNA inhibited cell growth, induced apoptosis, and decreased number of colony formation. Finally, HOTAIR modulated c-KIT expression by competitively binding miR-193a. Collectively, our data suggest that HOTAIR plays an important oncogenic role in AML and might serve as a marker for AML prognosis and a potential target for therapeutic intervention.
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                Author and article information

                Journal
                Journal of Cellular Physiology
                J Cell Physiol
                Wiley
                00219541
                May 2019
                May 2019
                September 24 2018
                : 234
                : 5
                : 6161-6172
                Affiliations
                [1 ]Department of Clinical Hematologic Laboratory; Jilin Medical University; Jilin China
                [2 ]Department of Pathology and Institute of Precision Medicine; Jining Medical University; Jining China
                [3 ]Department of Infectious Disease; No. 222 Hospital of PLA; Jilin China
                [4 ]Department of Pathogenic Biology; Jining Medical University; Jining China
                [5 ]Department of Pathophysiology; Jilin Medical University; Jilin China
                Article
                10.1002/jcp.27393
                30246348
                27964760-f814-4c11-aa31-c9fe125be169
                © 2018

                http://doi.wiley.com/10.1002/tdm_license_1.1

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