Long noncoding RNA ERLR mediates epithelial-mesenchymal transition of retinal pigment epithelial cells and promotes experimental proliferative vitreoretinopathy

Abstract

Proliferative vitreoretinopathy (PVR) is a disease that causes severe blindness and is characterized by the formation of contractile fibrotic subretinal or epiretinal membranes. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a hallmark of PVR. This work aims to examine the role of a long noncoding RNA (lncRNA) named EMT-related lncRNA in RPE (ERLR, LINC01705-201 (ENST00000438158.1)) in PVR and to explore the underlying mechanisms. In this study, we found that ERLR is upregulated in RPE cells stimulated with transforming growth factor (TGF)-β1 as detected by lncRNA microarray and RT-PCR. Further studies characterized full-length ERLR and confirmed that it is mainly expressed in the cytoplasm. In vitro, silencing ERLR in RPE cells attenuated TGF-β1-induced EMT, whereas overexpressing ERLR directly triggered EMT in RPE cells. In vivo, inhibiting ERLR in RPE cells reduced the ability of cells to induce experimental PVR. Mechanistically, chromatin immunoprecipitation (ChIP) assays indicated that the transcription factor TCF4 directly binds to the promoter region of ERLR and promotes its transcription. ERLR mediates EMT by directly binding to MYH9 protein and increasing its stability. TCF4 and MYH9 also mediate TGF-β1-induced EMT in RPE cells. Furthermore, ERLR is also significantly increased in RPE cells incubated with vitreous PVR samples. In clinical samples of PVR membranes, ERLR was detected through fluorescent in situ hybridization (FISH) and colocalized with the RPE marker pancytokeratin (pan-CK). These results indicated that lncRNA ERLR is involved in TGF-β1-induced EMT of human RPE cells and that it is involved in PVR. This finding provides new insights into the mechanism and treatment of PVR.

Prognostication of Pancreatic Cancer Using The Cancer Genome Atlas Based Ferroptosis-Related Long Non-Coding RNAs

“…In addition, LINC01705 has high expression during the pathogenesis of proliferative vitreoretinopathy ( Xie et al, 2018 ). Shuai Yang et al (2021) investigated the inhibitory effect of the tumor growth suppressor TRAF3IP2-AS1 on the progression of NONO-TFE3-translocated renal carcinoma and found that the overexpression of TRaf3IP2-AS1 could stimulate N6-methyladenosine of PARP1 mRNA and downregulate PTEN, further inhibiting the progression of renal carcinoma. He et al (2021) showed that TRAF3IP2-AS1 may be an attractive therapeutic target for IL-17-related autoimmune diseases, such as psoriasis and multiple sclerosis.…”

Molecular Insights into Tumor Targeted Therapy by Carrier-Free Lycorine Nanoparticles in Vitro and in Vivo

“…EMT has attracted more and more attention in promoting tumor cell invasion and metastasis [39][40][41]. In this study, we also determined the protein levels of two speci c EMT markers, E-cadherin and Vimentin.…”

Ligand-independent Activation of Platelet-derived Growth Factor Receptor β promotes contraction of retinal pigment epithelial cells

“…When RPEM cells grew to 90% con uence in 24-well culture plates, they were serum-starved overnight and then treated with RV or RV in the presence of NAC, SU6656 for additional 48 hours. The resultant lysates were subjected to western blot using desired antibodies, among which there was an antibody against α-SMA, a protein marker of EMT [40,41].…”