A Pilot Study on MicroRNA Profile in Tear Fluid to Predict Response to Anti-VEGF Treatments for Diabetic Macular Edema

Chan, Hwei Wuen; Yang, Binxia; Wong, Wai P.; Blakeley, Paul; Seah, Ivan; Tan, Queenie Shu Woon; Wang, Haofei; Bhargava, Mayuri; Lin, Hazel Anne; Chai, Charmaine; Mangunkusumo, Erlangga Ariadarma; Naing, Thet; Yuen, Yew Sen; Sethi, Raman; Wang, Si; Hunziker, Walter; Gopal, Lingam; Su, Xinyi

doi:10.3390/jcm9092920

Cited by 13 publications

(13 citation statements)

References 75 publications

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“…The other top-ranked miRNAs identified by bioinformatic analysis were miR-4500 and miR-4458. However, we did not find any literature on the role of miR-4500 and miR-4458 in endothelial dysfunction, whereas recent reports [52][53][54] have suggested a role for miR-98-5p in endothelial cells. Moreover, the complementary nucleotides between the target region of TMPRSS2 3′ untranslated region (3′-UTR) and miR-98-5p are evolutionarily highly conserved across different species, including humans, non-human primates, and rodents (Figure 1).…”

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confidence: 99%

miR-98 Regulates TMPRSS2 Expression in Human Endothelial Cells: Key Implications for COVID-19

et al. 2020

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The two main co-factors needed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter human cells are angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Here, we focused on the study of microRNAs that specifically target TMPRSS2. Through a bioinformatic approach, we identified miR-98-5p as a suitable candidate. Since we and others have shown that endothelial cells play a pivotal role in the pathogenesis of the coronavirus disease 2019 (COVID-19), we mechanistically validated miR-98-5p as a regulator of TMPRSS2 transcription in two different human endothelial cell types, derived from the lung and from the umbilical vein. Taken together, our findings indicate that TMPRSS2 represents a valid target in COVID-19 treatment, which may be achieved by specific non-coding-RNA approaches.

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confidence: 99%

miR-98 Regulates TMPRSS2 Expression in Human Endothelial Cells: Key Implications for COVID-19

et al. 2020

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“…Through bioinformatics analysis, Matarese et al also identified miR-4500 and miR-4458 [218]. However, no evidence exists in the literature about their endothelial dysfunction roles, while other reports [220][221][222] precisely suggest a role for miR-98-5p in endothelial cells. TMPRSS2 is a highly polymorphic gene, and specific genetic variants of TMPRSS2 have been classified, indicating that their frequencies change with geographic location and origin [223][224][225].…”

Section: Alternative Approachmentioning

confidence: 99%

Anti-SARS-CoV-2 Strategies and the Potential Role of miRNA in the Assessment of COVID-19 Morbidity, Recurrence, and Therapy

Narożna

Rubiś

2021

IJMS

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Recently, we have experienced a serious pandemic. Despite significant technological advances in molecular technologies, it is very challenging to slow down the infection spread. It appeared that due to globalization, SARS-CoV-2 spread easily and adapted to new environments or geographical or weather zones. Additionally, new variants are emerging that show different infection potential and clinical outcomes. On the other hand, we have some experience with other pandemics and some solutions in virus elimination that could be adapted. This is of high importance since, as the latest reports demonstrate, vaccine technology might not follow the new, mutated virus outbreaks. Thus, identification of novel strategies and markers or diagnostic methods is highly necessary. For this reason, we present some of the latest views on SARS-CoV-2/COVID-19 therapeutic strategies and raise a solution based on miRNA. We believe that in the face of the rapidly increasing global situation and based on analogical studies of other viruses, the possibility of using the biological potential of miRNA technology is very promising. It could be used as a promising diagnostic and prognostic factor, as well as a therapeutic target and tool.

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“…1 The main cause of DME is the onset of macular thickening. 17 VEGF overexpression plays a pivotal role in DME progression, but its mechanism and diagnostic role have remained elusive. Serum exosomal miRNAs have been identified as biomarkers of several diseases, although their value in DME has been unclear.…”

Section: Discussionmentioning

confidence: 99%

Serum exosomal miR-377-3p inhibits retinal pigment epithelium proliferation and offers a biomarker for diabetic macular edema

et al. 2021

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Objectives Diabetic macular edema (DME) is a complication of diabetes mellitus that leads to diabetic retinopathy. Thus far, the role of serum exosomal microRNAs (miRNAs) in DME progression remains elusive. This study investigated serum exosomal miRNAs from patients with type 2 diabetes (T2D) and DME to identify miRNAs associated with expression of vascular endothelial growth factor (VEGF), a pivotal component in DME progression; it also evaluated the diagnostic values of these miRNAs for DME. Methods Serum was collected from patients with T2D who did (n = 20) and did not have DME (n = 24). Exosomes were isolated from serum and subjected to real-time polymerase chain reaction, western blotting, luciferase reporter, and miRNA profiling analyses. Results VEGF was significantly upregulated in ARPE-19 cells treated with exosomes from patients with T2D and DME, compared with exosomes from patients with T2D alone. Among the top 10 downregulated miRNAs identified during exosomal miRNA profiling, miR-377-3p inhibited the expression of VEGF. Luciferase reporter assays confirmed that miR-377-3p could directly regulate VEGF expression. Receiver operating characteristic analysis identified serum exosomal miR-377-3p as a potential biomarker for DME. Conclusion Serum exosomal miR-377-3p inhibits VEGF expression to suppress retinal pigment epithelium proliferation and offers a diagnostic biomarker for DME.

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A Pilot Study on MicroRNA Profile in Tear Fluid to Predict Response to Anti-VEGF Treatments for Diabetic Macular Edema

Cited by 13 publications

References 75 publications

miR-98 Regulates TMPRSS2 Expression in Human Endothelial Cells: Key Implications for COVID-19

miR-98 Regulates TMPRSS2 Expression in Human Endothelial Cells: Key Implications for COVID-19

Anti-SARS-CoV-2 Strategies and the Potential Role of miRNA in the Assessment of COVID-19 Morbidity, Recurrence, and Therapy

Serum exosomal miR-377-3p inhibits retinal pigment epithelium proliferation and offers a biomarker for diabetic macular edema

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