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

Li, Tong; Xu, Jianguo; Liu, Yi

doi:10.3389/fcell.2021.757260

“…Therefore, this study aims to screen out new prognostic markers of cervical cancer and reduce the mortality of cervical cancer patients, thereby providing reference for improving the prognosis and realizing individualized targeted therapy. PDIA3 affects the occurrence and development of a variety of cancer tissues and regulates the proliferation of cancer cells, playing a vital role in the prognosis and treatment of malignant tumors [19]. The research by Zou et al [20] suggested that patients with glioma with high PDIA3 expression had poor survival prognosis, and PDIA3 could be used as an independent prognostic biomarker of diffuse glioma, whose down-regulation might contribute to the survival of patients undergoing chemotherapy and radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

Expression and Prognostic Significance of PDIA3 in Cervical Cancer

Zhang

¹

,

Li

²

,

Li

³

et al. 2022

International Journal of Genomics

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To investigate the expression of protein disulfide isomerase A3 (PDIA3/ERP57) in cervical cancer and its clinical prognostic significance as well as its function and possible action mechanism in the progression of cervical cancer. Based on TIMER2.0 database, the human protein map (Human Protein Atlas) was used to determine the expression level of PDIA3 protein for the analysis of PDIA3 expression in 39 The Cancer Genome Atlas (TCGA) tumors. The PDIA3 expression in cervical cancer tissues in the TCGA and Genotype-Tissue Expression databases was further verified based on the GEPIA2 database to analyze the relationship between the PDIA3 expression and the pathological stage of cervical cancer patients. Immunohistochemistry was used to detect the PDIA3 expression in cervical cancer tissue microarray, including 111 cancer tissue samples and 24 adjacent cancer tissue samples, and the relationship between PDIA3 protein expression and clinical characteristics of patients with cervical cancer was analyzed. The Kaplan–Meier method and log-rank test were used for survival analysis. Based on the cBioPortal database, the Spearman’s and Pearson’s methods were used to analyze the correlation between PDIA3 expression and DNA methylation. The correlation between PDIA3 expression and the infiltration levels of each immune cell in cervical cancer was evaluated. The STRING was used to construct protein interaction network. Based on LinkedOmics database, the Spearman’s method was used to analyze the co-expressed genes of PDIA3 in TCGA cervical cancer. The gene ontology functional enrichment analysis was performed on Top 50 differentially co-expressed genes based on DAVID database. The PDIA3 expression in cervical cancer tissues was significantly higher than that in normal tissues, which ( F = 2.74 , PR (>F) = 0.0436) was significantly increased with the progression of tumor stage, and PDIA3 showed strong immunoreactivity in cervical cancer tissues. In cervical cancer patients, overall survival ( P = 0.014 ), disease-specific survival ( P = 0.013 ), disease-free interval ( P = 0.023 ), and progression-free interval ( P = 0.001 ) in those with high expression of PDIA3 were significantly lower than those with low expression, suggesting that high expression of PDIA3 was associated with poor prognosis. In cervical cancer, high expression of PDIA3 was associated with DNA methylation and negatively correlated with B cell memory ( r = − 0.132 , P = 0.021 ), T cell regulatory ( r = − 0.127 , P = 0.026 ), monocytes ( r = − 0.204 , P = 0 ), and macrophages M2 ( r = − 0.142 , P = 0.013 ), whereas positively correlated with levels of NK cell activated ( r = 0.162 , P = 0.005 ) and mast cells activated ( r = 0.119 , P = 0.037 ). The genes positively correlated with PDIA3 expression included HSPA5 and PPIB, which were mainly enriched in biological processes, such as endoplasmic reticulum (ER) protein folding and ER stress response. PDIA3 can be used as a marker of poor prognosis of cervical cancer. The expression level of PDIA3 is closely related to the survival and prognosis of cervical cancer patients, DNA methylation, and immune cell infiltration.

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“…Based on the results of the subcellular fractionation and FISH assays, circ-TRIO was located in the cytoplasm of TNBC cells, indicating that circ-TRIO might have the potential to sponge miRNAs. To date, numerous studies have shown that acting as miRNA sponges is among the most significant approaches by which circRNAs exert their functions [44][45][46]. CiRS-7 was the first circRNA that has been proven to exert its functions by acting as a miRNA sponge, possessing more than 70 conventional binding sites for miR-7 [47].…”

Section: Discussionmentioning

confidence: 99%

Circ-TRIO promotes TNBC progression by regulating the miR-432-5p/CCDC58 axis

Wang

¹

,

Li

²

,

Yang

³

et al. 2022

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Numerous studies have shown that circRNAs are aberrantly expressed in various cancers and play a significant role in tumor progression. However, the molecular mechanisms of circRNAs in triple-negative breast cancer (TNBC) remain ambiguous. By intersecting throughput data and qRT-PCR results from tissues and cell lines, circ-TRIO was identified as a potential oncogenic regulator of TNBC. Moreover, circ-TRIO expression was detected in TNBC tissues and was correlated with the recurrence and prognosis of TNBC patients. The circular characteristics of circ-TRIO were verified by RNase R and CHX assays. Functionally, the knockdown of circ-TRIO inhibited the proliferation, migration and invasion of TNBC cells, while the overexpression of circ-TRIO resulted in the opposite impacts. Mechanistically, a dual luciferase reporter assay and RNA immunoprecipitation were performed and indicated that circ-TRIO could combine with miR-432-5p to regulate the expression of coiled-coil domain containing 58 (CCDC58). In summary, our study illustrates that circ-TRIO plays an important role in the progression of TNBC by regulating the miR-432-5p/CCDC58 axis, which could broaden our insight into the underlying mechanisms and provide a novel prognostic marker of TNBC in the clinic.

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“…CircRFX3 is generated from the RFX3 gene [ 93 ]. A high circRFX3 expression level was related to poor prognosis in GBM patients.…”

Section: Functional Mechanisms Of Circrnas In Gbmmentioning

confidence: 99%

“…A high circRFX3 expression level was related to poor prognosis in GBM patients. Overexpression of circRFX3 promoted GBM cell proliferation, invasion and migration [ 93 ]. Dual-luciferase and RNA pull-down assays revealed that circRFX3 could sponge miR-587 and that PDIA3 was a direct target of miR-587 [ 93 ].…”

Section: Functional Mechanisms Of Circrnas In Gbmmentioning

confidence: 99%

Underlying mechanisms and clinical potential of circRNAs in glioblastoma

ZHANG,

GAO

et al. 2023

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Glioblastoma (GBM) is the most malignant form of glioma and is difficult to diagnose, leading to high mortality rates. Circular RNAs (circRNAs) are noncoding RNAs with a covalently closed loop structure. CircRNAs are involved in various pathological processes and have been revealed to be important regulators of GBM pathogenesis. CircRNAs exert their biological effects by 4 different mechanisms: serving as sponges of microRNAs (miRNAs), serving as sponges of RNA binding proteins (RBPs), modulating parental gene transcription, and encoding functional proteins. Among the 4 mechanisms, sponging miRNAs is predominant. Their good stability, broad distribution and high specificity make circRNAs promising biomarkers for GBM diagnosis. In this paper, we summarized the current understanding of the characteristics and action mechanisms of circRNAs, illustrated the underlying regulatory mechanisms of circRNAs in GBM progression and explored the possible diagnostic role of circRNAs in GBM.

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

Cited by 10 publications

References 24 publications

Expression and Prognostic Significance of PDIA3 in Cervical Cancer

Expression and Prognostic Significance of PDIA3 in Cervical Cancer

Circ-TRIO promotes TNBC progression by regulating the miR-432-5p/CCDC58 axis

Underlying mechanisms and clinical potential of circRNAs in glioblastoma

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