OIP5-AS1 modulates epigenetic regulator HDAC7 to enhance non-small cell lung cancer metastasis via miR-140-5p
ONCOLOGY LETTERS
Authors: Mei, Jiazhuan; Liu, Guiju; Wang, Wenhui; Xiao, Peng; Yang, Dan; Bai, Hua; Li, Ruijun
Abstract
Long non-coding RNAs have been reported to be involved in non-small cell lung cancer (NSCLC) progression. However, whether Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) serves a role in NSCLC remains unclear. Bioinformatics analysis of The Cancer Genome Atlas datasets showed clinical significance and relevance of OIP5-AS1 in NSCLC. Western blotting and reverse transcription-quantitative PCR revealed protein and RNA expression levels of the genes [includingOIP5-AS1, microRNA (miR)-140-5p, histone deacetylase 7(HDAC7)and vascular endothelial growth factor A(VEGFA)]. Direct associations between the genes (miR-140-5p and OIP5-AS1, or miR-140-5p and HDAC7) were confirmed using a dual-luciferase reporter assay. Lymphatic vessel formation and invasion ability were detected using a lymphatic vessel formation assay and Transwell invasion assay. OIP5-AS1 knockdown attenuated lymphatic vessel length and invasion. The role of OIP5-AS1 was reverted by miR-140-5p. HDAC7 and VEGFA are downstream effectors of miR-140-5p-mediated NSCLC metastasis. OIP5-AS1, miR-140-5p, HDAC7 and VEGFA were all dysregulated in human clinical NSCLC tumor tissues. In conclusion, the present results demonstrated a novel mechanism for OIP5-AS1-induced metastatic phenotypes of NSCLC via the miR-140-5p/HDAC7/VEGFA axis.
Retinal VEGFA maintains the ultrastructure and function of choriocapillaris by preserving the endothelial PLVAP
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Authors: Kim, Sang A.; Kim, Soo Jin; Choi, Yeong A.; Yoon, Hye-Jin; Kim, Anna; Lee, Junyeop
Abstract
Fenestrations in choriocapillaris act as a window for molecular transports between the retina and choroid, and is crucial for maintaining visual function. Plasmalemma vesicle-associated protein (PLVAP) is essential for the development of endothelial fenestrations. There is little knowledge about how the choriocapillaris maintains the fenestrated endothelium. This study aimed to evaluate the role of vascular endothelial growth factor-A (VEGFA)-PLVAP axis in the maintenance of choroidal fenestrations using oxygen-induced retinopathy (OIR) model. In C57BL/6 J mice, the mice with OIR on postnatal day 12 (P12) presented thicker endothelium and less fenestration compared to the non-OIR mice. However, the OIR on 17 mice showed thinner endothelium with more fenestration compared to OIR on P12. In vivo angiography demonstrated the presence of hyperpermeable choroidal vessels on P17 in OIR mice. These dramatic changes in choriocapillaris were not observed in the BALB/cJ OIR model. The ultrastructural changes in the choriocapillaris were correlated with temporal variations in the expression of VEGFA and PLVAP. VEGFA stimulated expression of PLVAP in the choroidal endothelial cells. Loss of PLVAP disrupts the polarized structure of the choriocapillaris leading to retinal degeneration. These results indicate that the expression of retinal VEGFA is essential for maintaining the structure and function of choriocapillaris by preserving the endothelial PLVAP. (C) 2019 The Authors. Published by Elsevier Inc.