Dataset Information

Profiling of circular RNAs in age-related cataract reveals circZNF292 as an antioxidant by sponging miR-23b-3p.

ABSTRACT: Age-related cataract (ARC) is one of the major causes of visual impairment and reversible blindness worldwide. Accumulating evidence has revealed that circular RNAs (circRNAs) are involved in multiple regulatory processes in various ocular diseases. However, the expression profile, regulatory roles, and underlying mechanisms of circRNAs in ARC remain largely unknown. Herein we deep-sequenced circRNAs of anterior lens capsules from normal and ARC lenses, and detected 23,787 candidate circRNAs. Of these, 466 were significantly differentially expressed, and a higher correlation in down-regulated circRNAs between ARC and diabetic cataract was observed compared with up-regulated ones. Subsequent bioinformatics analysis disclosed that certain differentially expressed circRNAs participated in oxidative stress and apoptosis-related signaling pathways in ARC. Notably, the level of circZNF292 was significantly decreased, while miR-23b-3p was significantly increased in ARC. The target region prediction and dual-luciferase reporter assays proved that circZNF292 acted as a competitive endogenous RNA to regulate the expression of anti-oxidative genes through competing with miR-23b-3p. Our results indicate that circZNF292, a down-regulated circRNA in the anterior lens capsule of ARC patients, may be involved in resistance to oxidative damage and apoptosis of lens epithelial cells by sponging miR-23b-3p, providing a potential target for prevention and treatment of ARC.

SUBMITTER: Liang S

PROVIDER: S-EPMC7521481 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Profiling of circular RNAs in age-related cataract reveals circZNF292 as an antioxidant by sponging miR-23b-3p.

Liang Shuqi S Dou Shengqian S Li Wenfeng W Huang Yusen Y

Aging 20200910 17

Age-related cataract (ARC) is one of the major causes of visual impairment and reversible blindness worldwide. Accumulating evidence has revealed that circular RNAs (circRNAs) are involved in multiple regulatory processes in various ocular diseases. However, the expression profile, regulatory roles, and underlying mechanisms of circRNAs in ARC remain largely unknown. Herein we deep-sequenced circRNAs of anterior lens capsules from normal and ARC lenses, and detected 23,787 candidate circRNAs. Of ...[more]

PMID: 32913142

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Project description:Circular RNAs (circRNAs) have been identified from various tissues and species, but their regulatory functions during developmental processes are not well understood. We examined circRNA expression profiles of two developmental stages of bovine skeletal muscle (embryonic and adult musculus longissimus) to provide first insights into their potential involvement in bovine myogenesis. We identified 12 981 circRNAs and annotated them to the Bos taurus reference genome, including 530 circular intronic RNAs (ciRNAs). One parental gene could generate multiple circRNA isoforms, with only one or two isoforms being expressed at higher expression levels. Also, several host genes produced different isoforms when comparing development stages. Most circRNA candidates contained two to seven exons, and genomic distances to back-splicing sites were usually less than 50 kb. The length of upstream or downstream flanking introns was usually less than 105 nt (mean≈11 000 nt). Several circRNAs differed in abundance between developmental stages, and real-time quantitative PCR (qPCR) analysis largely confirmed differential expression of the 17 circRNAs included in this analysis. The second part of our study characterized the role of circLMO7-one of the most down-regulated circRNAs when comparing adult to embryonic muscle tissue-in bovine muscle development. Overexpression of circLMO7 inhibited the differentiation of primary bovine myoblasts, and it appears to function as a competing endogenous RNA for miR-378a-3p, whose involvement in bovine muscle development has been characterized beforehand. Congruent with our interpretation, circLMO7 increased the number of myoblasts in the S-phase of the cell cycle and decreased the proportion of cells in the G0/G1 phase. Moreover, it promoted the proliferation of myoblasts and protected them from apoptosis. Our study provides novel insights into the regulatory mechanisms underlying skeletal muscle development and identifies a number of circRNAs whose regulatory potential will need to be explored in the future.

Project description:As a recently discovered noncoding RNA, circular RNAs (circRNAs) have been identified to play key roles in cancer biology; however, the detailed functions and mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain largely unclarified. RNA-seq analysis was used to screen the expression profiles of circRNAs in HCC. CircZNF566 expression in HCC tissues and cell lines was detected by qRT-PCR. In vitro CCK-8, colony formation, wound healing, transwell migration, and invasion assays and in vivo tumorigenesis and metastasis assays were conducted to determine the functions of circZNF566. Luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were also performed to confirm the relationship between circZNF566 and miR-4738-3p. Bioinformatics analysis and luciferase reporter assays were employed to determine whether miR-4738-3p regulates tryptophan 2,3-dioxygenase (TDO2) expression. Finally, immunohistochemistry (IHC) was used to detect the level of TDO2 and determine its prognostic value. CircZNF566 was significantly upregulated in HCC tissues and cell lines. High circZNF566 expression in HCC tissues was positively correlated with clinicopathological features and poor prognosis. Functionally, in vitro experiments showed that circZNF566 promoted HCC cell migration, invasion, and proliferation, whereas in vivo experiments showed that circZNF566 promoted tumorigenesis and metastasis. Mechanistically, circZNF566 acted as a miR-4738-3p sponge to relieve the repressive effect of miR-4738-3p on its target TDO2. In addition, miR-4738-3p suppressed HCC cell migration, invasion, and proliferation, while TDO2 was positively correlated with pathological features and poor prognosis and promoted cell migration, invasion, and proliferation in HCC. CircZNF566 is a novel tumor promoter in HCC and functions through the circZNF566/ miR-4738-3p /TDO2 axis; in addition, circZNF566 may serve as a novel diagnostic marker, prognostic indicator, and target for the treatment of HCC.

Dataset Information

Profiling of circular RNAs in age-related cataract reveals circZNF292 as an antioxidant by sponging miR-23b-3p.

Publications

Profiling of circular RNAs in age-related cataract reveals circZNF292 as an antioxidant by sponging miR-23b-3p.

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