Abstract:Diabetic retinopathy (DR), as the most frequent microvascular complication of diabetes mellitus (DM), causes vision loss and blindness in adults worldwide with increasing incidence. MicroRNAs (miRNAs) are involved in the regulation of DR. However, the role of miR-542-5p is still unknown. Here, we demonstrate that miR-542-5p is down-regulated in patients with DR and in high-glucose (HG)-treated retinal pigment epithelial cells. Moreover, miR-542-5p overexpression inhibits apoptosis in retinal pigment epithelial… Show more
“…In this, the high expression of CARM1 also was found in DR patients and HG-induced RPE cells. Silencing CARM1 could effectively relieve HG-induced RPE cell injury, which was consistent with the results of previous studies [ 32 , 33 ]. In addition, we confirmed that CARM1 was targeted by miR-338-3p, and it could reverse the inhibitory effect of miR-338-3p on HG-induced RPE cell injury.…”
Section: Discussionsupporting
confidence: 92%
“…Under the condition of HG, CARM1 was discovered to be upregulated in RPE cells and promote cell apoptosis [ 32 ]. Moreover, Guo et al suggested that miR-542-5p could target CARM1 to inhibit HG-induced RPE cell apoptosis [ 33 ]. In this, the high expression of CARM1 also was found in DR patients and HG-induced RPE cells.…”
Background. Circular RNAs (circRNAs) have been reported to be involved in the regulation of retinal pigment epithelial (RPE) cell injury and are closely related to the development of diabetic retinopathy (DR). More research is needed to confirm the role and mechanism of circ-ADAM9 in DR progression. Methods. High glucose (HG)-induced RPE cells (ARPE-19) were used to mimic the hyperglycemia condition. The expression of circ-ADAM9, microRNA (miR)-338-3p, and coactivator-associated arginine methyltransferase 1 (CARM1) was measured using quantitative real-time PCR. Cell proliferation and apoptosis were determined using MTT assay, EdU assay, and flow cytometry. The protein expression of apoptosis markers and CARM1 was examined by the western blot analysis. Also, MDA level and SOD activity were determined to assess cell oxidative stress. In addition, the interaction between miR-338-3p and circ-ADAM9 or CARM1 was confirmed by dual-luciferase reporter assay and RIP assay. Results. The expression of circ-ADAM9 was upregulated in DR patients and HG-induced ARPE-19 cells. Silenced circ-ADAM9 could promote proliferation and inhibit inflammation, apoptosis, and oxidative stress in HG-induced ARPE9 cells. In terms of mechanism, circ-ADAM9 could sponge miR-338-3p to upregulate CARM1. The inhibitory effect of circ-ADAM9 knockdown on HG-induced ARPE9 cell injury could be reversed by an miR-338-3p inhibitor. As a target of miR-338-3p, CARM1 knockdown could alleviate HG-induced ARPE9 cells’ injury, and its overexpression also could reverse the negatively regulation of miR-338-3p on HG-induced ARPE9 cell injury. Conclusion. Circ-ADAM9 contributed to HG-induced ARPE9 cell injury by regulating miR-338-3p/CARM1 axis, which provided effective targets for DR treatment.
“…In this, the high expression of CARM1 also was found in DR patients and HG-induced RPE cells. Silencing CARM1 could effectively relieve HG-induced RPE cell injury, which was consistent with the results of previous studies [ 32 , 33 ]. In addition, we confirmed that CARM1 was targeted by miR-338-3p, and it could reverse the inhibitory effect of miR-338-3p on HG-induced RPE cell injury.…”
Section: Discussionsupporting
confidence: 92%
“…Under the condition of HG, CARM1 was discovered to be upregulated in RPE cells and promote cell apoptosis [ 32 ]. Moreover, Guo et al suggested that miR-542-5p could target CARM1 to inhibit HG-induced RPE cell apoptosis [ 33 ]. In this, the high expression of CARM1 also was found in DR patients and HG-induced RPE cells.…”
Background. Circular RNAs (circRNAs) have been reported to be involved in the regulation of retinal pigment epithelial (RPE) cell injury and are closely related to the development of diabetic retinopathy (DR). More research is needed to confirm the role and mechanism of circ-ADAM9 in DR progression. Methods. High glucose (HG)-induced RPE cells (ARPE-19) were used to mimic the hyperglycemia condition. The expression of circ-ADAM9, microRNA (miR)-338-3p, and coactivator-associated arginine methyltransferase 1 (CARM1) was measured using quantitative real-time PCR. Cell proliferation and apoptosis were determined using MTT assay, EdU assay, and flow cytometry. The protein expression of apoptosis markers and CARM1 was examined by the western blot analysis. Also, MDA level and SOD activity were determined to assess cell oxidative stress. In addition, the interaction between miR-338-3p and circ-ADAM9 or CARM1 was confirmed by dual-luciferase reporter assay and RIP assay. Results. The expression of circ-ADAM9 was upregulated in DR patients and HG-induced ARPE-19 cells. Silenced circ-ADAM9 could promote proliferation and inhibit inflammation, apoptosis, and oxidative stress in HG-induced ARPE9 cells. In terms of mechanism, circ-ADAM9 could sponge miR-338-3p to upregulate CARM1. The inhibitory effect of circ-ADAM9 knockdown on HG-induced ARPE9 cell injury could be reversed by an miR-338-3p inhibitor. As a target of miR-338-3p, CARM1 knockdown could alleviate HG-induced ARPE9 cells’ injury, and its overexpression also could reverse the negatively regulation of miR-338-3p on HG-induced ARPE9 cell injury. Conclusion. Circ-ADAM9 contributed to HG-induced ARPE9 cell injury by regulating miR-338-3p/CARM1 axis, which provided effective targets for DR treatment.
“…CARM1 accelerated retinal pigment epithelial cell apoptosis by mediating H3R17 asymmetric dimethylation, thereby promoting the progression of DR [28]. Additionally, Guo et al revealed that CARM1 up-regulation expedited cell apoptosis in HG-stimulated retinal pigment epithelial cells via binding to miR-542-5p [29]. In our research, we verified that CARM1 level was overtly elevated in DR patients and HG-disposed hRMECs.…”
Background
Diabetic retinopathy (DR) is a serious complication of diabetes. Numerous reports have validated that circular RNAs (circRNAs) participate in DR progression. This study aimed to elucidate the role and potential mechanism of circRNA zinc finger protein 532 (circZNF532) in DR.
Methods
The levels of circZNF532, miR-1243, and coactivator associated arginine methyltransferase 1 (CARM1) in DR patients and human retinal microvascular endothelial cells (hRMECs) were determined by quantitative real-time PCR and western blot. Colony formation assay, transwell assay, tube formation assay and enzyme-linked immunosorbent assay were used to assess the biological function of hRMECs. The binding relationship between miR-1243 and circZNF532/CARM1 was verified by dual-luciferase reporter and RNA immunoprecipitation assays.
Results
circZNF532 and CARM1 levels were increased, while miR-1243 level was reduced in DR patients and high glucose (HG)-stimulated hRMECs. In terms of mechanism, miR-1243 competitively bound to circZNF532 and CARM1. Down-regulation of circZNF532 restrained HG-induced hRMECs proliferation, migration, invasion, angiogenesis and inflammation via regulating miR-1243. In addition, miR-1243 inhibited HG-triggered hRMECs progression via targeting CARM1.
Conclusion
circZNF532 facilitated HG-induced angiogenesis and inflammation in hRMECs via modulating the miR-1243/CARM1 pathway, suggesting that circZNF532 might be a potential biomarker for DR treatment.
“…MiR-34a was a promoter in DR progression by targeting sirtuin-1 (SIRT1), 30 and miR-542-5p was an antipathogenic factor in DR by targeting coactivator-associated arginine methyltransferase 1 (CARM1). 31 HG was found to increase the expression of miR-128-3p in this study. The functional assays exhibited that miR-128-3p expression upregulation neutralized all those effects of HG on ARPE-19 cells.…”
:Diabetic retinopathy is a frequent complication of diabetes mellitus and one of the common causes of blindness. Circular RNAs (circRNAs) can modulate various biological behaviors of human diseases. Circ_0084043 is a novel circRNA, and its function in diabetic retinopathy progression is unclear. Adult retinal pigment epithelial cells (ARPE-19) were treated with high glucose (HG). RNA levels of circ_0084043, microRNA-128-3p (miR-128-3p), and thioredoxin-interacting protein (TXNIP) were detected by quantitative real-time polymerase chain reaction. 3-(4, 5-dimethylthiazole-2-y1)-2, 5-diphenyl tetrazolium bromide and flow cytometry were, respectively, used to examine cell viability and apoptosis. Apoptotic and TNXIP relative protein levels were measured by Western blot. The combination between targets was analyzed through dual-luciferase reporter assay or RNA immunoprecipitation assay. Results showed that HG induced the upregulation of circ_0084043 and the downregulation of miR-128-3p in ARPE-19 cells. Circ_0084043 knockdown or miR-128-3p overexpression mitigated the HG-mediated cell viability inhibition, apoptosis promotion, and inflammatory response. Circ_0084043 targeted miR-128-3p and miR-128-3p inhibitor returned the regulation of si-circ_0084043 in HG-treated cells. TXNIP was the target gene of miR-128-3p and TXNIP overexpression abolished the miR-128-3p-mediated effects after HG treatment. Circ_0084043 regulated the TXNIP expression to activate Wnt/β-catenin signal pathway by targeting miR-128-3p. Our findings unraveled that circ_0084043 promoted the HG-induced retinal pigment epithelial cell injury through activating the Wnt/β-catenin signal pathway by the miR-128-3p/TXNIP axis. Circ_0084043 might be an available biomarker in diabetic retinopathy diagnosis and therapy.
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