Circular RNA circ-NT5C2 acts as an oncogene in osteosarcoma proliferation and metastasis through targeting miR-448

Liu, Xunfa; Zhong, Yun‐Shi; Li, Jifeng; Shan, Aijun

doi:10.18632/oncotarget.22162

Cited by 49 publications

(52 citation statements)

References 30 publications

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“…circular RNAs have been confirmed to exert various effects, including functioning as biomarkers to improve the diagnostic efficiency and serving as a regulatory factor in OS progression (12,(31)(32)(33). In the study by Liu et al, it was reported that circNT52 functioned as an oncogene to regulate OS cell proliferation and metastasis by sponging miR-448 (34). circSAMd4A has been reported to be highly expressed in OS and to regulate cell proliferation by targeting the miR-1244/MdM2 axis (27).…”

Section: Discussionmentioning

confidence: 99%

CircSAMD4A regulates cell progression and epithelial‑mesenchymal transition by sponging miR‑342‑3p via the regulation of FZD7 expression in osteosarcoma

Xie

Chen

et al. 2020

Int J Mol Med

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Osteosarcoma (OS) is a primary malignant tumor with a complex etiology. Therefore, research into the pathogenesis of osteosarcoma is considered a priority. circular RNAs play important roles in cell metabolism and in the immune response and are closely associated with cancer treatment. However, research into the association of circular RNAs with osteosarcoma is limited. In the present study, circSAMd4A was validated by RT-qPcR and agarose gel electrophoresis. circSAMd4A and miR-342-3p expression was detected by RT-qPcR. The relative protein expression levels were measured by western blot analysis. MTT assay and flow cytometry were used to detect cell cytotoxicity and apoptosis, respectively. Transwell assay was applied to assess cell migration and invasion. dual-luciferase reporter assay was used to determine the association among circSAMd4A, Frizzled-7 (FZd7) and miR-342-3p. In vivo, subcutaneous tumor formation assay was performed in an experiment with nude mice. The results revealed that the expression levels of circSAMd4A and FZd7 were upregulated, while those of miR-342-3p were downregulated in OS tissues and cells. The inhibition of circSAMd4A suppressed cell progression and epithelial-mesenchymal transition (EMT), and promoted cell apoptosis in OS. The reduction of miR-342-3p reversed the effects of circSAMd4A downregulation on cell cytotoxicity, migration, invasion, apoptosis and EMT in OS, while FZd7 overexpression blocked the effect of miR-342-3p upregulation on OS progression. The suppressive effect of sh-circSAMd4A on tumor growth was thus verified in OS. Overall, the present study demonstrated that circSAMd4A affected cell cytotox-icity, invasion, apoptosis, migration and EMT by regulating the miR-342-3p/FdZ7 axis in OS, thereby providing a novel regulatory mechanism and a potential therapeutic target for OS.

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Section: Discussionmentioning

confidence: 99%

CircSAMD4A regulates cell progression and epithelial‑mesenchymal transition by sponging miR‑342‑3p via the regulation of FZD7 expression in osteosarcoma

Xie

Chen

et al. 2020

Int J Mol Med

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“…Overall, results showed that hsa_circ_0016788 accelerated the HCC via miR-486/CDK4 and acted as a biomarker for HCC detection. in series of pathogenesis, including cancers, circulation system disease, and nervous system disease (Hsiao, Sun, & Tsai, 2017;Li, Ding, et al, 2017;Liu, Zhong, Li, & Shan, 2017). In present study, our project devotes ourself to the expression profiles of circRNAs in hepatocellular carcinoma (HCC) tissue and investigate the potential pathological effects on HCC oncogenesis.…”

Section: Hsa_circ_0016788 Accelerated the Hcc Via Mir-486/cdk4 And mentioning

confidence: 99%

Circular RNA hsa_circ_0016788 regulates hepatocellular carcinoma tumorigenesis through miR‐486/CDK4 pathway

Zheng

Tan

et al. 2018

Journal Cellular Physiology

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Recent studies have revealed that circular RNAs (circRNAs) play important roles in the tumorigenesis of human cancer, including hepatocellular carcinoma (HCC). In present study, we screen the circular RNA expression profiles in HCC tissue and investigate the molecular roles on HCC tumorigenesis. Human circRNA microarray analysis showed there were total 1,245 differently expressed circular RNAs, including 756 up-regulated circRNAs and 489 down-regulated circRNAs, in three pairs of HCC tissue and adjacent normal tissue. Hsa_circ_0016788 was identified to be up-regulated in both HCC tissue and cell lines. Loss-of-functional experiments in vivo and vitro revealed that hsa_circ_0016788 silencing inhibited the proliferation, invasion and promoted the apoptosis in vitro, and inhibited the tumor growth in vivo. Bioinformatics tools and luciferase reporter assay validated that miR-486 targeted hsa_circ_0016788 and CDK4 accompanying with negatively correlated expression, suggesting the hsa_circ_0016788/miR-486/CDK4 pathway. Receiver operating characteristic (ROC) curve showed that hsa_circ_0016788 had high diagnostic value (AUC = 0.851). In summary, results reveal the role of hsa_circ_0016788/miR-486/CDK4 in HCC tumorigenesis, providing a novel therapeutic target for HCC.

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“…Moreover, 22 studies were further eliminated with a variety of reasons, including ve studies not related to circRNAs or osteosarcoma, six studies did not report outcomes, two reviews and case reports, four animal studies, and ve lack of extractable data. Finally, 26 studies comprising 1,652 osteosarcoma cases were enrolled in this quantitative study, with 18 on clinicopathological features, ten on diagnosis [13,18,19,21,24,[30][31][32][33][34] [12,14,18,19,[32][33][34][36][37][38][39][40], whereas other two studies on downregulated circRNAs applying ≥ 18 or < 18 years old to separate enrolled patients [13,30]. In consideration of the consistency, only these studies with common cut-off value were included in the following meta-analysis with regard to patients' age.…”

Section: Characteristics Of the Enrolled Studiesmentioning

confidence: 99%

“…The duration for follow-up ranged from 40 to 125. For diagnostic assay, ten studies with data on sensitivity, speci city and AUC [13,18,19,21,24,[30][31][32][33][34]. The quality of studies was evaluated by QUADAS II and NOS scores.…”

Section: Characteristics Of the Enrolled Studiesmentioning

confidence: 99%

“…More recently, emerging studies have highlighted the role of circRNAs in osteosarcoma [12][13][14][15][16][17][18][19]. CircRNAs are reported to modulate osteosarcoma malignant properties including cell proliferation, apoptosis, migration and resistance to chemotherapy [12,20,21]. CircRNAs could interact with cancer-related signaling pathway, such as Akt/GSK-3β, and wnt/β-catenin pathway, or act as a ceRNA to sponge miRNA and consequently regulate target genes in osteosarcoma progression [12,22,23].…”

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confidence: 99%

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Diagnostic and Prognostic Significance of Dysregulated Expression of Circular RNAs in Osteosarcoma

Zhang

et al. 2020

Preprint

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Background CircRNAs have emerged as pivotal regulators in osteosarcoma tumorigenesis and progression, but their prognostic and diagnostic significance remain unclear. Herein, we aimed to perform an updated meta-analysis to explore the clinical, diagnostic and prognostic values of circRNAs in osteosarcoma. Methods Several databases, including PubMed, Web of Science, EMBASE, Scopus and Cochrane Library, were systematically searched up to April 10, 2020. Eligible studies regarding the relationship between circRNAs levels and clinicopathological, diagnostic and prognostic values in osteosarcoma patients were included in this study. Pooled odds ratios with corresponding 95% confidence intervals were used to measure clinical characteristics, while hazard ratios with 95% CIs were adopted to assess overall survival (OS) and disease-free survival (DFS). Results Overall, 26 relevant studies involving 1,652 patients with osteosarcoma were enrolled, with eighteen studies on clinicopathological parameters, ten on diagnosis and eighteen on prognosis. For clinical parameters, overexpression of oncogenic circRNAs was intimately correlated with larger tumor size (P < 0.00001), advanced Enneking stage (P < 0.00001), poor differentiation (P = 0.0001), and distant metastasis (DM) (P < 0.00001). In contrast, the downregulated circRNAs showed negative correlation with Enneking stage (P = 0.002) and DM (P < 0.0001). For the diagnostic values, the summary area under the curve of circRNA for the discriminative efficacy between osteosarcoma patients and non-cancer counterparts was estimated to be 0.86 (95% CI: 0.83–0.89), with a weighted sensitivity of 0.80 (95% CI: 0.74–0.84), specificity of 0.80 (95%: 0.75–0.84), and diagnostic odds ratio of 15.48 (10.85–22.10), respectively. For the prognostic significance, oncogenic circRNAs had poor OS (HR = 1.92, 95% CI: 1.68–2.19) and DFS (HR = 2.65, 95% CI: 2.02–3.49), while elevated expression of tumor-suppressor circRNAs were closely related to longer OS (HR = 0.44, 95% CI: 0.28–0.69). Conclusions Taken together, our study showed that aberrantly expressed circRNA signatures could serve as potential biomarkers in diagnosis and prognosis in patients with osteosarcoma.

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Circular RNA circ-NT5C2 acts as an oncogene in osteosarcoma proliferation and metastasis through targeting miR-448

Cited by 49 publications

References 30 publications

CircSAMD4A regulates cell progression and epithelial‑mesenchymal transition by sponging miR‑342‑3p via the regulation of FZD7 expression in osteosarcoma

CircSAMD4A regulates cell progression and epithelial‑mesenchymal transition by sponging miR‑342‑3p via the regulation of FZD7 expression in osteosarcoma

Circular RNA hsa_circ_0016788 regulates hepatocellular carcinoma tumorigenesis through miR‐486/CDK4 pathway

Diagnostic and Prognostic Significance of Dysregulated Expression of Circular RNAs in Osteosarcoma

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