Dataset Information

Long noncoding RNA UCA1 from hypoxia-conditioned hMSC-derived exosomes: a novel molecular target for cardioprotection through miR-873-5p/XIAP axis.

ABSTRACT: Exosomes (Exo) secreted from mesenchymal stem cells (hMSCs) are protective against myocardial injury. The purpose of the study was to investigate the role and mechanisms by which exosomes promote cardiomyocyte survival and function following myocardial infarction (MI). hMSCs were cultured under hypoxic and normoxic conditions. Hypoxia-conditioned hMSC-derived exosomes (Hypo-Exo) and normoxic-conditioned hMSC-derived exosomes (Nor-Exo) were collected and intramyocardially injected into rats with MI. The therapeutic effects of Hypo-Exo and Nor-Exo were evaluated after 4 weeks. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of candidate long noncoding RNA urothelial carcinoma associated 1 (lncRNA-UCA1) in Nor-Exo and Hypo-Exo. Intramyocardial injection of lncRNA-UCA1-knockdown-Hypo-Exo in a rat model of MI was then performed and the cardiac function was characterized. The target and downstream of the molecular mechanism lncRNA-UCA1 was disclosed by luciferase reporter assays and western blot. Circulating exosomal lncRNA-UCA1 level in AMI patients and healthy volunteers was assessed. We found that (1) hMSC exosomal (from hypoxic and normoxic conditions) cardioprotection in vitro and in vivo correlated with the presence of encapsulated lncRNA-UCA1 in exosomes; (2) lncRNA-UCA1 targeted miR-873 via sponging, reducing the latter's suppressive effects on its target XIAP, and this translated into AMPK phosphorylation and increased level of the antiapoptotic protein BCL2; and (3) plasma derived from patients with AMI contained exosomes enriched with the lncRNA-UCA1, unlike that from normal subjects. This study demonstrates that Hypo-Exo lncRNA-UCA1 plays a cardioprotective role via the miR-873-5p/XIAP axis and circulating exosomal lncRNA-UCA1 may be a promising novel biomarker for the diagnosis of AMI.

SUBMITTER: Sun L

PROVIDER: S-EPMC7442657 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Long noncoding RNA UCA1 from hypoxia-conditioned hMSC-derived exosomes: a novel molecular target for cardioprotection through miR-873-5p/XIAP axis.

Sun Ling L Zhu Wenwu W Zhao Pengcheng P Wang Qingjie Q Fan Baohan B Zhu Yeqian Y Lu Yao Y Chen Qiushi Q Zhang Jian J Zhang Fengxiang F

Cell death & disease 20200810 8

Exosomes (Exo) secreted from mesenchymal stem cells (hMSCs) are protective against myocardial injury. The purpose of the study was to investigate the role and mechanisms by which exosomes promote cardiomyocyte survival and function following myocardial infarction (MI). hMSCs were cultured under hypoxic and normoxic conditions. Hypoxia-conditioned hMSC-derived exosomes (Hypo-Exo) and normoxic-conditioned hMSC-derived exosomes (Nor-Exo) were collected and intramyocardially injected into rats with ...[more]

PMID: 32826854

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Project description:Background: Hypoxia is a crucial factor in the progression of various tumors, including gastric cancer (GC). Circular RNAs (circRNAs) are important regulators in GC, and this study focused on researching circC6orf132 in GC progression under hypoxia. Methods: In vitro experiments were performed in GC cells under hypoxia (1% O2). CircC6orf132, microRNA-873-5p (miR-873-5p), and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) levels were examined by real-time polymerase chain reaction (qRT-PCR). Colony formation assay and transwell assay were used for detecting cell proliferation and migration or invasion. Glycolytic metabolism was evaluated using lactate production, glucose uptake, and adenosine triphosphate (ATP) level and extracellular acidification rate (ECAR). Western blotting was performed for determining protein expression. The target interaction was analyzed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. In vivo assay was conducted via mouse xenograft model. Results: The expression of circC6orf132 was significantly high in GC cells under hypoxia. Hypoxia-induced GC proliferation, migration, invasion, and glycolysis were reversed by silencing circC6orf132. CircC6orf132 targeted miR-873-5p; and the inhibition of circC6orf132 knockdown for the effects of hypoxia on GC cells was abrogated by miR-873-5p inhibitor. PRKAA1 was validated as a downstream gene of miR-873-5p, and miR-873-5p functioned as an anticancer molecule in GC cells under hypoxia by downregulating PRKAA1 level. CircC6orf132 could regulate PRKAA1 by sponging miR-873-5p. CircC6orf132/miR-873-5p/PRKAA1 axis could regulate GC progression under the hypoxic condition. CircC6orf132 downregulation reduced tumorigenesis in vivo through affecting the miR-873-5p/PRKAA1 axis. Conclusion: CircC6orf132 has been affirmed to promote proliferation, migration, invasion, and glycolysis in GC under hypoxia, partly by depending on the regulation of miR-873-5p/PRKAA1 axis.

Project description:Background: DC-STAMP domain containing 1-antisense 1 (DCST1-AS1) is a long noncoding RNA (lncRNA) that is up-regulated in triple-negative breast cancer (TNBC) tissues. Here, we attempt to investigate the oncogenic property of DCST1-AS1. Methods: LncRNA microarrays were used to detect differentially expressed lncRNA in cancerous tissues. Fluorescence in situ hybridization assay was used to detect the distribution of DCST1-AS1 in BT-549 and MDA-MB-231 cells. Lentiviral systems, inhibitors, siRNA and overexpression plasmids were used for gain- and loss-of-function experiments. Colony formation assay, wound healing assay, CCK8 assay, transwell assay, and flow cytometry assay were used to study the function of DCST1-AS1. Luciferase assay was used to verify the binding of MYC to the promoter region and the binding of miR-873-5p to DCST1-AS1. RNA immunoprecipitation assay was used to verify that argonaute 2 binds to both miR-873-5p and DCST1-AS1. Western blotting was used to measure changes in protein expression. Results: Consistent with the microarray results, we found that DCST1-AS1 was up-regulated in both TNBC tissue samples and cell lines. DCST1-AS1 was positively correlated with distant metastasis and histopathological grades. DCST1-AS1 is distributed in both nucleus and cytoplasm. Knockdown of DCST1-AS1 inhibits TNBC cell proliferation and metastasis, while overexpression of DCST1-AS1 promotes TNBC cell proliferation and metastasis. We confirmed that DCST1-AS1 expression in TNBC cells is regulated by MYC. Furthermore, we found that DCST1-AS1 is negatively correlated with miR-873-5p in TNBC tissues and is a direct target gene of miR-873-5p. Argonaute 2 is involved in the binding of DCST1-AS1 and miR-873-5p and promotes the degradation of DCST1-AS1. The interaction of DCST1-AS1 with miR-873-5p ultimately up-regulated the expression of insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), MYC, CD44 and lymphoid enhancer binding factor 1 (LEF1). Conclusions: DCST1-AS1 is activated by MYC and is degraded by binding to miR-873-5p, thereby upregulating the expression of miR-873-5p downstream proteins IGF2BP1, MYC, LEF1 and CD44. MYC, DCST1-AS1 and miR-873-5p form a positive regulatory loop to promote TNBC cell proliferation and metastasis.

Dataset Information

Long noncoding RNA UCA1 from hypoxia-conditioned hMSC-derived exosomes: a novel molecular target for cardioprotection through miR-873-5p/XIAP axis.

Publications

Long noncoding RNA UCA1 from hypoxia-conditioned hMSC-derived exosomes: a novel molecular target for cardioprotection through miR-873-5p/XIAP axis.

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