Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function

Josipovic, Ivana; Pflüger, Beatrice; Fork, Christian; Vasconez, Andrea E.; Oo, James A.; Hitzel, Juliane; Seredinski, Sandra; Gamen, Elisabetta; Heringdorf, Dagmar Meyer zu; Chen, Wei; Looso, Mario; Pullamsetti, Soni Savai; Brandes, Ralf P.; Leisegang, Matthias

doi:10.1016/j.yjmcc.2018.01.015

Cited by 36 publications

(43 citation statements)

References 57 publications

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“…Long noncoding RNAs (lncRNAs) constitute a large class of mRNA-like transcripts, greater than 200 nucleotides with no protein coding capability [6,7]. They are involved in a large variety of biological processes, with reports linking the dysregulation of lncRNAs with cancer cell invasion, proliferation and metastasis through mechanisms ranging from transcriptional levels to posttranscriptional levels [8,9].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation

Han¹,

Gu²,

Lü³

et al. 2020

Mol Cancer

149

126

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Background: Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Recent evidence suggests that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and chemoresistance. However, the regulatory mechanism of lncRNAs in trastuzumab resistance is not well established to date. In this research, we identified the differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer.Methods: LncRNA microarray and qRT-PCR were performed to identify the dysregulated lncRNAs. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of exosomal AFAP1-AS1 (actin filament associated protein 1 antisense RNA 1). Bioinformatics prediction, RNA fluorescence in situ hybridization (RNA-FISH) and immunoprecipitation assays were performed to identify the direct interactions between AFAP1-AS1 and other associated targets, such as AU-binding factor 1 (AUF1) and ERBB2. Finally, a series gain-or loss-functional assays were done to prove the precise role of AFAP1-AS1 in trastuzumab resistance.Results: AFAP1-AS1 was screened out due to its higher expression in trastuzumab-resistant cells compared to sensitive cells. Increased expression of AFAP1-AS1was associate with poorer response and shorter survival time of breast cancer patients. AFAP1-AS1 was upregulated by H3K27ac modification at promoter region, and knockdown of AFAP1-AS1 reversed trastuzumab resistance. Moreover, extracellular AFAP1-AS1 secreted from trastuzumab resistant cells was packaged into exosomes and then disseminated trastuzumab resistance of receipt cells. Mechanically, AFAP1-AS1 was associated with AUF1 protein, which further promoted the translation of ERBB2 without influencing the mRNA level.Conclusion: Exosomal AFAP1-AS1 could induce trastuzumab resistance through associating with AUF1 and promoting ERBB2 translation. Therefore, AFAP1-AS1 level may be useful for prediction of trastuzumab resistance and breast cancer treatment.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation

Han¹,

Gu²,

Lü³

et al. 2020

Mol Cancer

149

126

View full text Add to dashboard Cite

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“…Normal EC function is maintained by a gene program under the regulation of LSS, which antagonizes vascular disease (14). Previous studies have demonstrated LSS-responsive lncRNAs, including LINC00341 (29), MANTIS (9), LEENE (10), and LISPR1 (30). SENCR is shown here to be induced by LSS in multiple EC types; however, DSS, which promotes vascular disease (15), showed no observable impact on SENCR RNA level in cultured HUVEC.…”

Section: Discussionmentioning

confidence: 55%

SENCRstabilizes vascular endothelial cell adherens junctions through interaction with CKAP4

Lyu

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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SENCR is a human-specific, vascular cell-enriched long-noncoding RNA (lncRNA) that regulates vascular smooth muscle cell and endothelial cell (EC) phenotypes. The underlying mechanisms of action of SENCR in these and other cell types is unknown. Here, levels of SENCR RNA are shown to be elevated in several differentiated human EC lineages subjected to laminar shear stress. Increases in SENCR RNA are also observed in the laminar shear stress region of the adult aorta of humanized SENCR-expressing mice, but not in disturbed shear stress regions. SENCR loss-of-function studies disclose perturbations in EC membrane integrity resulting in increased EC permeability. Biotinylated RNA pull-down and mass spectrometry establish an abundant SENCR-binding protein, cytoskeletal-associated protein 4 (CKAP4); this ribonucleoprotein complex was further confirmed in an RNA immunoprecipitation experiment using an antibody to CKAP4. Structure–function studies demonstrate a noncanonical RNA-binding domain in CKAP4 that binds SENCR. Upon SENCR knockdown, increasing levels of CKAP4 protein are detected in the EC surface fraction. Furthermore, an interaction between CKAP4 and CDH5 is enhanced in SENCR-depleted EC. This heightened association appears to destabilize the CDH5/CTNND1 complex and augment CDH5 internalization, resulting in impaired adherens junctions. These findings support SENCR as a flow-responsive lncRNA that promotes EC adherens junction integrity through physical association with CKAP4, thereby stabilizing cell membrane-bound CDH5.

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“…RNA immunoprecipitation (RIP) experiments were performed in a similar manner as . Briefly, HUVECs UV‐crosslinked at 254 nm were scratched and resuspended in lysis buffer (50 m m Tris‐HCl pH7.4, 100 m m NaCl, 1% NP‐40, 0.1% SDS, 0.5% Sodium deoxycholate and protease inhibitors).…”

Section: Methodsmentioning

confidence: 99%

The histone demethylase PHF8 facilitates alternative splicing of the histocompatibility antigen HLA‐G

Leisegang

Preussner

et al. 2019

FEBS Letters

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Histone3‐lysine9 (H3K9) residues not only control gene expression, but also contribute to RNA splicing. Here, the H3K9 histone demethylase PHF8 was investigated in endothelial cells for its involvement in alternative splicing. An angiogenic sprouting assay shows the importance of PHF8 for endothelial cells. Immunoprecipitation reveals that PHF8 interacts with U1 spliceosomal proteins, such as SRPK1 and snRNP70. We identify the histocompatibility antigen HLA‐G as a target of PHF8. The inclusion of HLA‐G intron 4, with concomitant RNA Polymerase II accumulation at this intron is controlled by PHF8 and H3K9. Soluble HLA‐G is generated after PHF8 knockdown, which leads to reduced T‐cell proliferation. Collectively, PHF8 knockdown generates the immunosuppressive alternative splice product soluble HLA‐G, which is secreted by endothelial cells to elicit a potential inhibitory effect on inflammation.

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Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function

Cited by 36 publications

References 57 publications

RETRACTED ARTICLE: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation

RETRACTED ARTICLE: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation

SENCRstabilizes vascular endothelial cell adherens junctions through interaction with CKAP4

The histone demethylase PHF8 facilitates alternative splicing of the histocompatibility antigen HLA‐G

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