Dataset Information

Long noncoding RNA HAS2-AS1 accelerates non-small cell lung cancer chemotherapy resistance by targeting LSD1/EphB3 pathway.

ABSTRACT: The essential roles of long noncoding RNA (lncRNA) have been identified by emerging literature in the non-small cell lung cancer (NSCLC). However, the role of lncRNA hyaluronan synthase 2 antisense 1 (HAS2-AS1) in the NSCLC tumorigenesis is not clear. Here, we investigate the role and mechanism of HAS2-AS1 in the NSCLC tumorigenesis. In the NSCLC tissue and cells, HAS2-AS1 was found to be up-regulated, which, in turn, indicated the poor prognosis of NSCLC patients. Functional experiments illustrated that HAS2-AS1 promoted the proliferation, invasion and gefitinib chemotherapy resistance of NSCLC cells. In vivo, HAS2-AS1 knockdown suppressed the tumor growth. Mechanically, HAS2-AS1 recruited the lysine-specific demethylase 1 (LSD1) to the EphB3 promoter region to inhibit its transcription. In conclusion, this finding elucidates the essential roles of HAS2-AS1 in the NSCLC tumorigenesis, providing a possible treatment strategy for the NSCLC.

SUBMITTER: Sun P

PROVIDER: S-EPMC7137060 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Long noncoding RNA HAS2-AS1 accelerates non-small cell lung cancer chemotherapy resistance by targeting LSD1/EphB3 pathway.

Sun Peng P Sun Limin L Cui Jia J Liu Lili L He Qing Q

American journal of translational research 20200315 3

The essential roles of long noncoding RNA (lncRNA) have been identified by emerging literature in the non-small cell lung cancer (NSCLC). However, the role of lncRNA hyaluronan synthase 2 antisense 1 (HAS2-AS1) in the NSCLC tumorigenesis is not clear. Here, we investigate the role and mechanism of HAS2-AS1 in the NSCLC tumorigenesis. In the NSCLC tissue and cells, HAS2-AS1 was found to be up-regulated, which, in turn, indicated the poor prognosis of NSCLC patients. Functional experiments illustr ...[more]

PMID: 32269726

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Project description:BackgroundDiabetic retinopathy (DR) is a leading cause of blindness in the working-age population, which is characterized by retinal neurodegeneration and vascular dysfunction. Long non-coding RNAs (LncRNAs) have emerged as critical regulators in several biological processes and disease progression. Here we investigated the role of lncRNA AQP4-AS1 in retinal neurovascular dysfunction induced by diabetes.MethodsQuantitative RT-PCR was used to detect the AQP4-AS1 expression pattern upon diabetes mellitus-related stresses. Visual electrophysiology examination, TUNEL staining, Evans blue staining, retinal trypsin digestion and immunofluorescent staining were conducted to detect the role of AQP4-AS1 in retinal neurovascular dysfunction in vivo. MTT assays, TUNEL staining, PI/Calcein-AM staining, EdU incorporation assay transwell assay and tube formation were conducted to detect the role of AQP4-AS1 in retinal cells function in vitro. qRT-PCR, western blot and in vivo studies were conducted to reveal the mechanism of AQP4-AS1-mediated retinal neurovascular dysfunction.FindingsAQP4-AS1 was significantly increased in the clinical samples of diabetic retinopathy patients, high glucose-treated Müller cells, and diabetic retinas of a murine model. AQP4-AS1 silencing in vivo alleviated retinal neurodegeneration and vascular dysfunction as shown by improved retinal capillary degeneration, decreased reactive gliosis, and reduced RGC loss. AQP4-AS1 directly regulated Müller cell function and indirectly affected endothelial cell and RGC function in vitro. Mechanistically, AQP4-AS1 regulated retinal neurovascular dysfunction through affecting AQP4 levels.InterpretationThis study reveals AQP4-AS1 is involved in retinal neurovascular dysfunction and expected to become a promising target for the treatment of neurovascular dysfunction in DR.FundingThis work was generously supported by the grants from the National Natural Science Foundation of China (Grant No. 81800858, 82070983, 81870679 and 81970823), grants from the Medical Science and Technology Development Project Fund of Nanjing (Grant No ZKX17053 and YKK19158), grants from Innovation Team Project Fund of Jiangsu Province (No. CXTDB2017010), and the Science and Technology Development Plan Project Fund of Nanjing (Grant No 201716007, 201805007 and 201803058).

Dataset Information

Long noncoding RNA HAS2-AS1 accelerates non-small cell lung cancer chemotherapy resistance by targeting LSD1/EphB3 pathway.

Publications

Long noncoding RNA HAS2-AS1 accelerates non-small cell lung cancer chemotherapy resistance by targeting LSD1/EphB3 pathway.

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