LncRNA-encoded polypeptide ASRPS inhibits triple-negative breast cancer angiogenesis

Wang, Yirong; Wu, Siqi; Zhu, Xiaozhong; Zhang, Liyuan; Deng, Jieqiong; Li, Fang; Guo, Binbin; Zhang, Shenghua; Wu, Rui; Zhang, Zheng; Wang, Kexin; Lü, Jiachun; Zhou, Yifeng

doi:10.1084/jem.20190950

Cited by 150 publications

(112 citation statements)

References 46 publications

(53 reference statements)

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“…The lncRNAs are a newly recognized mechanism for gene regulation and are being explored as potential therapeutic targets in a variety of diseases (Li et al, 2018;Pecero et al, 2019;Wang et al, 2020), including diabetic nephropathy (Ge et al, 2019;Yang et al, 2019). A nucleic acid-based approach could allow greater specificity than pharmacological compounds, reducing side effects and allowing tissue-specific delivery (Sharma and Watts, 2015;Ku et al, 2016).…”

Section: Figure 8 | Ko Of Edn1-as Regulatory Elements Results In Incrmentioning

confidence: 99%

EDN1-AS, A Novel Long Non-coding RNA Regulating Endothelin-1 in Human Proximal Tubule Cells

et al. 2020

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Endothelin-1 (ET-1) is a peptide hormone that functions as a vasoconstrictor in the vasculature, whereas in the collecting duct of the kidney it exerts blood pressurelowering effects via natriuretic actions. Aberrant ET-1 signaling is associated with several pathological states including hypertension and chronic kidney disease. ET-1 expression is regulated largely through transcriptional control of the gene that encodes ET-1, EDN1. Here we report a long, non-coding RNA (lncRNA) that appears to be antisense to the EDN1 gene, called EDN1-AS. Because EDN1-AS represents a potential novel mechanism to regulate ET-1 expression, we examined the regulation of EDN1-AS expression and action. A putative glucocorticoid receptor response (GR) element upstream of the predicted EDN1-AS transcription start site was identified using the ENCODE database and the UCSC genome browser. Two homozygous deletion clones of the element were generated using CRISPR/Cas9. This deletion resulted in a significant increase in the expression of EDN1-AS, which was associated with increased secretion of ET-1 peptide from HK-2 cells (two-fold increase in KO cells vs. CNTL, n = 7, P < 0.05). Phenotypic characterization of these CRISPR clones revealed a difference in cell growth rates. Using a standard growth assay, we determined that the KO1 clone exhibited a three-fold increase in growth over 8 days compared to control cells (n = 4, P < 0.01) and the KO2 clone exhibited a two-fold increase (n = 4, P < 0.01). These results support a role for EDN1-AS as a novel regulatory mechanism of ET-1 expression and cellular proliferation.

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Section: Figure 8 | Ko Of Edn1-as Regulatory Elements Results In Incrmentioning

confidence: 99%

EDN1-AS, A Novel Long Non-coding RNA Regulating Endothelin-1 in Human Proximal Tubule Cells

et al. 2020

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“…51 In addition, long ncRNA encoded 60-amino acid polypeptide (ASRPS), centromere protein U, endogenous hydrogen sulfide, and exosomal-annexin A2 have been found to be associated with angiogenesis and suggested to be potential targets. [52][53][54][55]…”

Section: Angiogenesis Inhibitorsmentioning

confidence: 99%

<p>Progress: Targeted Therapy, Immunotherapy, and New Chemotherapy Strategies in Advanced Triple-Negative Breast Cancer</p>

Shi

Liu

Song

2020

CMAR

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Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, accounting for approximately 15% of cases, and is defined by the lack of expression of hormone receptors (estrogen and progesterone receptors) and lack of amplification or overexpression of human epidermal growth receptor 2 (HER2). Due to the lack of targets of hormone receptors and HER2, treatment of TNBC or advanced TNBC relies on conventional chemotherapeutic agents, but their efficacy and prognosis are poor. In patients with advanced TNBC, poorer outcomes are observed. Recently, with the launch of clinical trials and advancements in molecular studies, targeted therapy for signaling transduction pathways, immunotherapy for immune checkpoints, and new chemotherapy strategies have provided feasible or potential therapeutic options for advanced TNBC. This review aimed to summarize recent progress in targeted therapy, immunotherapy, and chemotherapy for advanced TNBC.

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“…The regulatory mechanisms of lncRNA vary depending on their location in the nucleus or cytoplasm ( 17 ). Numerous studies have reported that lncRNAs serve key roles in pathogenesis of various diseases, including cancer, cardiovascular diseases, nervous system disease and immune diseases ( 18 - 21 ). Certain lncRNAs are involved in autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) ( 22 - 24 ).…”

Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA expression profiles identify lncRNA‑XLOC_I2_006631 as a potential novel blood biomarker for Hashimoto's thyroiditis

et al. 2020

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Long non-coding RNAs (lncRNAs) have been increasingly recognized as important immune checkpoints involved in the pathogenesis of autoimmune diseases. However, the exact role of lncRNAs in Hashimoto's thyroiditis (HT) has been rarely studied. The aim of the present study was to investigate the role of lncRNAs and the potential biomarkers in HT, a total of 33 patients with HT and 32 healthy volunteers were enrolled in the present study, and five patients and five healthy controls were investigated using next generation sequencing. A total of 218 dysregulated lncRNAs, including 94 upregulated and 124 downregulated lncRNAs, were identified and examined in the peripheral blood mononuclear cells (PBMCs) from patients with HT. The majority of the lncRNAs were intergenic and exonic (66.06%). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that abnormally expressed lncRNAs were enriched in the 'NF-kB expression', in the 'TGF-β signaling pathway' and in the 'JAK-STAT signaling pathway', which are associated with the immunopathogenic mechanisms of HT. In total, three lncRNAs (LOC729737, XLOC_I2_006631 and BC041964) were validated and had a trend identical to that detected by the sequencing results. The expression of lncRNA-XLOC_I2_006631 was upregulated and was positively correlated with the serum concentrations of anti-thyroperoxidase antibody in patients with HT. Methyl-CpG-binding protein 2 (MECP2) was identified as the potential regulatory gene of lncRNA-XLOC_I2_006631 using a prediction program. The expression of MECP2 was increased and was positively correlated with the elevated expression levels of lncRNA-XLOC_I2_006631 and anti-thyroperoxidase antibody in patients with HT. Furthermore, lncRNA-XLOC_I2_006631 was able to regulate MECP2 expression in vitro . Receiver operating characteristic curve analysis suggested that lncRNA-XLOC_I2_006631 has a potential diagnostic value. Collectively, the present results indicated the important role of dysregulated lncRNAs in HT and demonstrated that lncRNA-XLOC_I2_006631 functioned as a positive regulator of MECP2 expression, suggesting a potential mechanism. Thus, lncRNA-XLOC_I2_006631 may be used as a biomarker of HT.

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LncRNA-encoded polypeptide ASRPS inhibits triple-negative breast cancer angiogenesis

Cited by 150 publications

References 46 publications

EDN1-AS, A Novel Long Non-coding RNA Regulating Endothelin-1 in Human Proximal Tubule Cells

EDN1-AS, A Novel Long Non-coding RNA Regulating Endothelin-1 in Human Proximal Tubule Cells

<p>Progress: Targeted Therapy, Immunotherapy, and New Chemotherapy Strategies in Advanced Triple-Negative Breast Cancer</p>

Long non‑coding RNA expression profiles identify lncRNA‑XLOC_I2_006631 as a potential novel blood biomarker for Hashimoto's thyroiditis

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