Circular RNAs: Novel target of diabetic retinopathy

Abstract Background Most of the biological functions of circular RNAs (circRNAs) and the potential underlying mechanisms in hepatocellular carcinoma (HCC) have not yet been discovered. Methods In this study, using circRNA expression data from HCC tumor tissues and adjacent tissues from the Gene Expression Omnibus database, we identified out differentially expressed circRNAs and verified them by qRT-PCT. Functional experiments were performed to evaluate the effects of circFAM13B in HCC in vitro and in vivo. Results We found that circFAM13B was the most significantly differentially expressed circRNA in HCC tissue. Subsequently, in vitro and in vivo studies also demonstrated that circFAM13B promoted the proliferation of HCC. Further studies revealed that circFAM13B, a sponge of miR-212, is involved in the regulation of E2F5 gene expression by competitively binding to miR-212, inhibits the activation of the P53 signalling pathway, and promotes the proliferation of HCC cells. Conclusions Our findings revealed the mechanism underlying the regulatory role played by circFAM13B, miR-212 and E2F5 in HCC. This study provides a new theoretical basis and novel target for the clinical prevention and treatment of HCC.

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Circ_0003266 sponges miR-503-5p to suppress colorectal cancer progression via regulating PDCD4 expression

BMC Cancer ◽

10.1186/s12885-021-07997-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Caihong Wen ◽

Xiaoqing Feng ◽

Honggang Yuan ◽

Yong Gong ◽

Guangsheng Wang

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Cell Lines ◽

Cancer Progression ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

Pdcd4 Expression ◽

Novel Target

Abstract Background Circular RNAs (circRNAs) feature prominently in tumor progression. However, the biological function and molecular mechanism of circ_0003266 in colorectal cancer (CRC) require further investigation. Methods Circ_0003266 expression in 46 pairs CRC tissues / adjacent tissues, and CRC cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR); after circ_0003266 was overexpressed or knocked down in CRC cells, cell proliferation, apoptosis, migration, and invasion were evaluated by the cell counting kit-8 (CCK-8), flow cytometry, and Transwell assays, respectively; the interaction among circ_0003266, miR-503-5p, and programmed cell death 4 (PDCD4) was confirmed using bioinformatics analysis and dual-luciferase reporter assay; PDCD4 protein expression in CRC cells was quantified using Western blot. Results Circ_0003266 was significantly lowly expressed in CRC tissues and cell lines. Circ_0003266 overexpression markedly repressed CRC cell proliferation, migration, and invasion, and accelerated the cell apoptosis, but its overexpression promoted the malignant phenotypes of CRC cells. PDCD4 was a direct target of miR-503-5p and circ_0003266 promoted PDCD4 expression by competitively sponging miR-503-5p. Conclusion Circ_0003266 suppresses the CRC progression via sponging miR-503-5p and regulating PDCD4 expressions, which suggests that circ_0003266 may serve as a novel target for the treatment of CRC.

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Silencing of hsa_circ_0000515 Inhibits Proliferation, Migration and Invasion of Gastric Cancer Cells by Sponging miR-615-5p In Vitro

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2733 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1466-1476

Author(s):

Xuli Wang ◽

Aiping Wang

Keyword(s):

Gastric Cancer ◽

Underlying Mechanism ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Pcr Analysis ◽

Circular Rnas ◽

Loss Of Function ◽

Gastric Cancer Cells ◽

Novel Target

Circular RNAs (circRNAs) have been reported to participate in the molecular mechanism of human cancers. This study investigates the role of circRNA hsa_circ_0000515 in gastric cancer (GC) cells and the underlying mechanism associated with microRNA-615-5p (miR-615-5p). qRT-PCR analysis showed the upregulation of hsa_circ_0000515 and downregulation of miR-615-5p in GC cell lines. Loss-of-function experiments indicated that suppression of hsa_circ_0000515 inhibited cell proliferation, migration, and invasion. Dual-luciferase reporter assay highlighted that hsa_circ_0000515 was able to act as a ceRNA of miR-615-5p. Furthermore, hsa_circ_0000515 could interact with splicing factors and bind miR-615-5p to regulate progression of GC cells. Deficiency of miR-615-5p reverses the inhibitory roles of si-hsa_circ_0000515 on the proliferation, migration, and invasion of GC cells. The findings highlighted the promising uses of hsa_circ_0000515 as a likely novel target for gastric cancer treatment.

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A Novel Circular RNA CircRFX3 Serves as a Sponge for MicroRNA-587 in Promoting Glioblastoma Progression via Regulating PDIA3

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.757260 ◽

2021 ◽

Vol 9 ◽

Author(s):

Tong Li ◽

Jianguo Xu ◽

Yi Liu

Keyword(s):

Circular Rna ◽

Molecular Therapy ◽

Luciferase Reporter ◽

Circular Rnas ◽

Competing Endogenous Rna ◽

Luciferase Reporter Gene ◽

Invasion And Migration ◽

Downstream Target ◽

Novel Target ◽

And Migration

An increasing number of studies have indicated that circular RNAs (circRNAs) participate in the progression of numerous tumors. However, the functions of circRNAs in glioblastoma (GBM) remain largely unknown. In this study, we focused on a novel circRNA (hsa_circRFX3_003) that was spliced from RFX3, which we named circRFX3. We confirmed that the expression of circRFX3 was substantially increased in GBM cell lines and clinical GBM tissues. The results of a series of overexpression and knockdown assays indicated that circRFX3 could boost the proliferation, invasion, and migration of GBM cells. By performing dual-luciferase reporter gene and RNA pull-down assays, we verified that circRFX3 could sponge microRNA-587 (miR-587) to exercise its function as a competing endogenous RNA (ceRNA) in the development of GBM. In addition, PDIA3 was proven to be a downstream target of miR-587 and to regulate the Wnt/β-catenin pathway. In conclusion, circRFX3 could act as a cancer-promoting circRNA to boost the development of GBM and regulate the miR-587/PDIA3/β-catenin axis. This study might provide a novel target for the treatment of GBM with molecular therapy.

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Amine oxidase copper-containing 3 (AOC3) inhibition: a potential novel target for the management of diabetic retinopathy

International Journal of Retina and Vitreous ◽

10.1186/s40942-021-00288-7 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

David S. Boyer ◽

Joerg F. Rippmann ◽

Michael S. Ehrlich ◽

Remko A. Bakker ◽

Victor Chong ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Visual Impairment ◽

Vascular Function ◽

Amine Oxidase ◽

Oral Treatment ◽

Unmet Need ◽

Treatment Burden ◽

Adhesion Protein ◽

Novel Target ◽

Vascular Adhesion

Abstract Background Diabetic retinopathy (DR), a microvascular complication of diabetes, is the leading cause of visual impairment in people aged 20–65 years and can go undetected until vision is irreversibly lost. There is a need for treatments for non-proliferative diabetic retinopathy (NPDR) which, in comparison with current intravitreal (IVT) injections, offer an improved risk–benefit ratio and are suitable for the treatment of early stages of disease, during which there is no major visual impairment. Efficacious systemic therapy for NPDR, including oral treatment, would be an important and convenient therapeutic approach for patients and physicians and would reduce treatment burden. In this article, we review the rationale for the investigation of amine oxidase copper-containing 3 (AOC3), also known as semicarbazide-sensitive amine oxidase and vascular adhesion protein 1 (VAP1), as a novel target for the early treatment of moderate to severe NPDR. AOC3 is a membrane-bound adhesion protein that facilitates the binding of leukocytes to the retinal endothelium. Adherent leukocytes reduce blood flow and in turn rupture blood vessels, leading to ischemia and edema. AOC3 inhibition reduces leukocyte recruitment and is predicted to decrease the production of reactive oxygen species, thereby correcting the underlying hypoxia, ischemia, and edema seen in DR, as well as improving vascular function. Conclusion There is substantial unmet need for convenient, non-invasive treatments targeting moderately severe and severe NPDR to reduce progression and preserve vision. The existing pharmacotherapies (IVT corticosteroids and IVT anti-vascular endothelial growth factor-A) target inflammation and angiogenesis, respectively. Unlike these treatments, AOC3 inhibition is predicted to address the underlying hypoxia and ischemia seen in DR. AOC3 inhibitors represent a promising therapeutic strategy for treating patients with DR and could offer greater choice and reduce treatment burden, with the potential to improve patient compliance.

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Circular RNA SFMBT2 Inhibits the Proliferation and Metastasis of Glioma Cells Through Mir-182-5p/Mtss1 Pathway

Technology in Cancer Research & Treatment ◽

10.1177/1533033820945799 ◽

2020 ◽

Vol 19 ◽

pp. 153303382094579

Author(s):

Shoudan Zhang ◽

Wanxiang Qin ◽

Shuo Yang ◽

Ning Guan ◽

Xin Sui ◽

...

Keyword(s):

High Mobility ◽

Glioma Cells ◽

Circular Rna ◽

Migration And Invasion ◽

Circular Rnas ◽

Metastasis Suppressor ◽

Metastasis Suppressor 1 ◽

Proliferation And Metastasis ◽

Novel Target

Glioma is a common type of tumor in human central nervous system, and it is characterized with high mobility and mortality. The prognosis of patients with advanced glioma remains poor. Thus, it is necessary to develop novel therapeutic approaches for the treatment of this disease. Circular RNAs are a group of noncoding RNAs which have been detected in eukaryotic cells. They are tissue-specific and characterized with a more stable structure compared with linear RNAs. Recently, studies have revealed that certain circular RNAs are involved in biological processes such as gene regulation; however, the functions of most circular RNAs remain unknown and require further investigation. Furthermore, circular RNAs can act as “sponges” of its target microRNA, consequently suppressing their activity. Additionally, impaired expression of circular RNAs is reported in different diseases including cancer. In our study, low expression of circular RNA Scm like with 4 Mbt domains 2 was detected in glioma samples. Furthermore, reduced circRNA Scm like with 4 Mbt domains 2 expression was observed in human glioma cell lines compared to normal astrocyte cells. Additionally, overexpression of circRNA Scm like with 4 Mbt domains 2 suppressed the growth and metastasis of glioma cells in vitro. Moreover, microRNA-182-5p could be a downstream molecule of circRNA Scm like with 4 Mbt domains 2. The influenced of microRNA-182-5p-induced proliferation, migration, and invasion of glioma cells could be abrogated by overexpressed circRNA Scm like with 4 Mbt domains 2. In addition, metastasis suppressor 1 was predicted as a novel target of microRNA-182-5p, and its expression was restored by circRNA Scm like with 4 Mbt domains 2. In summary, our findings provided novel insight into the roles of circRNA Scm like with 4 Mbt domains 2 in glioma. More importantly, circRNA Scm like with 4 Mbt domains 2/microRNA-182-5p/metastasis suppressor 1 axis could be a putative therapeutic target for the treatment of patients with glioma.

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Circular Ribonucleic Acid circFTO Promotes Angiogenesis and Impairs Blood–Retinal Barrier Via Targeting the miR-128-3p/Thioredoxin Interacting Protein Axis in Diabetic Retinopathy

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.685466 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jianjin Guo ◽

Feng Xiao ◽

Wei Ren ◽

Yikun Zhu ◽

Qiujing Du ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Vascular Endothelial Cells ◽

Cell Model ◽

Luciferase Reporter ◽

Circular Rnas ◽

Blood Retinal Barrier ◽

Interacting Protein ◽

Thioredoxin Interacting Protein

Background: Increasing attention has been attracted by the role of circular RNAs (circRNAs) in ocular diseases. Previous study has revealed that circ_0005941 (also known as circFTO, an alpha-ketoglutarate–dependent dioxygenase) was upregulated in the vitreous humor of diabetic retinopathy (DR), while its underlying mechanism in DR remains unknown.Methods: Retinal vascular endothelial cells (RVECs) treated with high glucose (HG) were used to establish the DR cell model. The in vivo assays were conducted using streptozotocin-induced diabetic mice. The circular structure and stability of circFTO were identified by Sanger sequencing and RNase R treatment. RT-qPCR analysis was used to detect the RNA expression. The levels of the mRNA-encoded protein thioredoxin-interacting protein (TXNIP) or angiogenesis-associated proteins (VEGFA, PDGF, and ANG2) and blood–retinal barrier (BRB)-related proteins (ZO-1, Occludin, and Claudin-5) were measured by Western blot. The viability of RVECs was measured using CCK-8 assays. The angiogenesis of RVECs was assessed using tube formation assays in vitro. Endothelial permeability assays were conducted to examine the function of the BRB. The binding between genes was explored using RNA pulldown and luciferase reporter assays.Results: CircFTO was upregulated in HG-treated RVECs. CircFTO deficiency reversed the HG-induced increase in the viability and angiogenesis of RVECs and alleviated HG-mediated impairment of the BRB. MiR-128-3p bound with circFTO and was downregulated in HG-treated RVECs. TXNIP was a downstream target gene of miR-128-3p. TXNIP was highly expressed in the DR cell model. Rescue assays revealed that circFTO promoted angiogenesis and impaired the blood–retinal barrier by upregulating TXNIP. In the DR mouse model, circFTO silencing inhibited angiogenesis and promoted BRB recovery in vivo.Conclusion: CircFTO promotes angiogenesis and impairs the blood–retinal barrier in vitro and in vivo by binding with miR-128-3p to upregulate TXNIP in DR.

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