LncRNA LINC00673 is Downregulated in Diabetic Retinopathy and Regulates the Apoptosis of Retinal Pigment Epithelial Cells via Negatively Regulating p53

Abstract

Background: Long noncoding RNA (LncRNA) LINC00673 has been proven to play critical roles in cancer biology, while its role in other diseases is unknown. It has been reported that LINC00673 could interact with p53, a critical player in diabetes and diabetic complications, suggesting that LINC00673 may also participate in diabetic retinopathy (DR). This study aimed to investigate the role of LINC00673 in DR. Methods: The present study included 3 groups of participants, including DR group, diabetes (DB) group, and healthy control (Control) group. Flow cytometry was utilized to determine cell apoptosis. Proteins and messenger RNAs (mRNAs) were estimated by Western blot and quantitative reverse transcription PCR (qRT-PCR), respectively. Results: LINC00673 was downregulated in plasma samples of DR patients (n=60) in comparison with the healthy controls (n=60) and negatively correlated with p53 only across DR patients but not across the healthy controls. In retinal pigment epithelial cells (RPECs), high glucose treatment downregulated LINC00673. Moreover, LINC00673 overexpression downregulated p53 and decreased RPEC apoptosis, while LINC00673 silencing upregulated p53 and increased RPEC apoptosis. In addition, p53 overexpression reduced the effects of LINC00673 overexpression. Conclusion: LINC00673 is downregulated in DR patients and regulates RPEC apoptosis via negatively regulating p53.

Impact of Long Noncoding RNA LINC00673 Genetic Variants on Susceptibility to Diabetic Retinopathy

“…Studies that have discussed the possible correlation between LINC00673 SNP and DR development are rare; only one study has evaluated the relationship between LINC00673 expression and DR ( Cheng et al, 2021 ). In our study, the frequency of LINC00673 SNPs (i.e., rs6501551, rs9914618, and rs11655237) was not significantly different between the non-DR and DR groups.…”

“…Nevertheless, research on the relationship between the SNPs of LINC00673 and DR development is rare. Because LINC00673 is downregulated in patients with DR ( Cheng et al, 2021 ), the SNPs of LINC00673 may also affect the clinical features of DR.…”

Noncoding RNAs Are Promising Therapeutic Targets for Diabetic Retinopathy: An Updated Review (2017–2022)

“…lncRNA H19 reduces inflammation by inhibiting miR-93 expression via XBP1s in HG-induced RPE cells [ 128 ]. Overexpression of lncRNA LINC00673 can downregulate the expression of p53, thereby inhibiting the apoptosis of RPE cells in HG conditions [ 129 ]. lncRNA AK077216 reduces ARPE-19 cell apoptosis by inhibiting the expression of miR-383 [ 130 ].…”

Diabetic Retinopathy: Are lncRNAs New Molecular Players and Targets?

“…Additionally, in a recent paper it has been observed that Mini-chromosome Maintenance Complex Component 3 Associated Protein Antisense ( MCM3AP-AS1 ) was downregulated in DR patients comparing to T2D subjects and promotes cell apoptosis by regulating miR-211/ SIRT1 axis [ 174 ]. Moreover, the downregulation of the Long Intergenic Non-Coding RNA 673 ( LINC00673 ) has been reported in plasma samples of DR patients [ 175 ]. Interestingly, LINC00673 induces apoptosis in retinal pigment epithelial cells (RPECs) under HG conditions by negatively regulating p53.…”

“…Interestingly, LINC00673 induces apoptosis in retinal pigment epithelial cells (RPECs) under HG conditions by negatively regulating p53. [ 175 ]. Interestingly, in a recent work from Sehgal and colleagues, the Vascular Endothelial-Associated LncRNA 2 ( VEAL2 ) has been identified as a novel lncRNA implicated in human vascular disease [ 176 ].…”