Downregulation of circulating miR-320a and target gene prediction in patients with diabetic retinopathy

Prado, Marcelle SanJuan Ganem; Jesus, Mirthz Lemos de; Goes, Thaline Cunha de; Mendonça, Lucilla Silva Oliveira; Kaneto, Carla Martins

doi:10.1186/s13104-020-05001-9

Cited by 23 publications

(17 citation statements)

References 47 publications

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“…A number of studies have indicated the role of miRNAs in tumors ( 29 , 30 ). miR-320a, which is an extensively studied miRNA, has been reported to serve a critical role in diabetic retinopathy ( 31 ) and atherosclerosis ( 32 ). Moreover, miR-320a has been investigated in several types of cancer, such as lung cancer ( 33 ), papillary thyroid cancer ( 34 ), osteosarcoma ( 35 ) and hepatocellular carcinoma ( 36 ).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of microRNA‑320a inhibits proliferation and induces apoptosis of retinoblastoma cells via targeting TUSC3

Kong¹,

Sun²,

Chen³

et al. 2020

Exp Ther Med

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MicroRNA (miR)-320a is specific to vertebrates and has been indicated to serve a role in a number of cancer types, such as gastric, colorectal, pancreatic and ovarian cancer. miR-320a has been reported to be expressed at high levels in retinoblastoma tissues; however its role and mechanism of function in retinoblastoma remain to be elucidated. The aim of the present study was to investigate the role of miR-320a in retinoblastoma cells and the underlying mechanisms. The expression of miR-320a in retinoblastoma cell lines Y79 and WERI-Rb-1, and normal human retinal pigment epithelial cell line ARPE-19 was examined via reverse transcription-quantitative PCR (RT-qPCR). TargetScan bioinformatics analysis and dual-luciferase reporter assay were used to predict and reveal the target gene of miR-320a. Target gene expression was detected via RT-qPCR in retinoblastoma cell lines and ARPE-19 cells. Subsequently, gain-or loss-of-function experiments for miR-320a and tumor suppressor candidate 3 (TUSC3) were performed to study the role of miR-320a/TUSC3 in retinoblastoma cells. Cell viability and apoptosis were assessed via MTT and flow cytometry analysis, respectively. Compared with ARPE-19 cells, miR-320a was prominently expressed in retinoblastoma cell lines. TUSC3 was predicted to be a target gene of miR-320a. Compared with ARPE-19 cells, the expression of TUSC3 in retinoblastoma cell lines was reduced. The results of MTT and flow cytometry analysis revealed that overexpression of TUSC3 reduced the viability of retinoblastoma cells and induced apoptosis. Additional analysis indicated that miR-320a inhibitor enhanced the expression of the target gene TUSC3, thereby inhibiting retinoblastoma cell viability and inducing apoptosis. The effects of miR-320a inhibitor on retinoblastoma cells were inhibited by TUSC3-short hairpin RNA. miR-320a regulated the viability and apoptosis of retinoblastoma cells via targeting TUSC3. Therefore, the present study provided a reference for investigating a potential target for the clinical treatment of retinoblastoma.

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Section: Introductionmentioning

confidence: 99%

Downregulation of microRNA‑320a inhibits proliferation and induces apoptosis of retinoblastoma cells via targeting TUSC3

Kong¹,

Sun²,

Chen³

et al. 2020

Exp Ther Med

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“…In addtion, using an RNA-Seq approach, it was evidenced that miR-4448, miR-338-3p, miR-190a-5p, miR-485-5p, and miR-9-5p appeared differentially expressed in serum from retinopathic diabetic patients when compared to controls (49). However, while validation of miR-21 and miR-126 in DR was confirmed in other similar studies (39,40,44,45), miR-320a, which was previously found to be upregulated in DR (23), was later reported to be significantly downregulated in another work (51), indicating, therefore, that discrepancies exist in this context. Several explanations can be provided for the lack of consensus in the literature in this regard.…”

Section: Discussionmentioning

confidence: 72%

“…In recent years, several works have investigated the association of miRNAs with DR (23)(24)(25)(26)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). In circulating miRNA profiling studies, miR-27b, miR-320a, and miR-126 were validated in patients with type 1 diabetes and DR (23,42).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-1281 as a Novel Circulating Biomarker in Patients With Diabetic Retinopathy

et al. 2020

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Objective: Recently, the role of circulating miRNAs as non-invasive biomarkers for the identification and monitoring of diabetes microvascular complications has emerged. Herein, we aimed to: identify circulating miRNAs differentially expressed in patients with and without diabetic retinopathy (DR); examine their predictive value; and understand their pathogenic impact. Methods: Pooled serum samples from randomly selected matched patients with type 2 diabetes, either with or without DR, were used for initial serum miRNA profiling. Validation of the most relevant miRNAs was thereafter conducted by RT-qPCR in an extended sample of patients with DR and matched controls. Results: Following miRNA profiling, 43 miRNAs were significantly up-or down-regulated in patients with DR compared with controls. After individual validation, 5 miRNAs were found significantly overexpressed in patients with DR. One of them, miR-1281, was the most up-regulated and appeared to be specifically related to DR. Furthermore, secreted levels of miR-1281 were increased in high glucose-cultured retinal cells, and there was evidence of a potential link between glucose-induced miR-1281 up-regulation and DR. Conclusion: Our findings suggest miR-1281 as a circulating biomarker of DR. Also, they highlight the pathogenic significance of miR-1281, providing insights for a new potential target in treating DR.

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“…DR is one of the most extensively studied diabetic complications, since it is a major cause of blindness and vision impairment among adults. Plasma levels of miR-320a are lower in patients with DR compared to patients with DM and no retinopathy and to healthy controls [ 89 ]. MiR-320 is also involved in the regulation of insulin growth factor-1 (IGF-1) expression, which takes part in the development of insulin resistance in adipose tissue and endothelial cells [ 89 ].…”

Section: C-reactive Proteinmentioning

confidence: 99%

“…Plasma levels of miR-320a are lower in patients with DR compared to patients with DM and no retinopathy and to healthy controls [ 89 ]. MiR-320 is also involved in the regulation of insulin growth factor-1 (IGF-1) expression, which takes part in the development of insulin resistance in adipose tissue and endothelial cells [ 89 ]. It is noteworthy that patients with DR presented with higher risk of AD compared to healthy controls, indicating the association between dysregulated miRNAs, DM, DR and AD [ 90 ].…”

Section: C-reactive Proteinmentioning

confidence: 99%

Early Biomarkers of Neurodegenerative and Neurovascular Disorders in Diabetes

Siwik

Gajewska

Jaguszewski

et al. 2020

JCM

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Diabetes mellitus (DM) is a common disease worldwide. There is a strong association between DM and neurovascular and neurodegenerative disorders. The first group mainly consists of diabetic retinopathy, diabetic neuropathy and stroke, whereas, the second group includes Alzheimer’s disease, Parkinson’s disease, mild cognitive impairment and dementia. The aforementioned diseases have a common pathophysiological background including insulin resistance, oxidative stress, atherosclerosis and vascular injury. The increasing prevalence of neurovascular and neurodegenerative disorders among diabetic patients has resulted in an urgent need to develop biomarkers for their prediction and/or early detection. The aim of this review is to present the potential application of the most promising biomarkers of diabetes-related neurodegenerative and neurovascular disorders, including amylin, β-amyloid, C-reactive protein (CRP), dopamine, gamma-glutamyl transferase (GGT), glycogen synthase kinase 3β, homocysteine, microRNAs (mi-RNAs), paraoxonase 1, phosphoinositide 3-kinases, tau protein and various growth factors. The most clinically promising biomarkers of neurovascular and neurodegenerative complications in DM are hsCRP, GGT, homocysteine and miRNAs. However, all biomarkers discussed in this review could become a part of the potential multi-biomarker screening panel for diabetic patients at risk of neurovascular and neurodegenerative complications.

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Downregulation of circulating miR-320a and target gene prediction in patients with diabetic retinopathy

Cited by 23 publications

References 47 publications

Downregulation of microRNA‑320a inhibits proliferation and induces apoptosis of retinoblastoma cells via targeting TUSC3

Downregulation of microRNA‑320a inhibits proliferation and induces apoptosis of retinoblastoma cells via targeting TUSC3

MicroRNA-1281 as a Novel Circulating Biomarker in Patients With Diabetic Retinopathy

Early Biomarkers of Neurodegenerative and Neurovascular Disorders in Diabetes

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