Circular RNA profile identifies circOSBPL10 as an oncogenic factor and prognostic marker in gastric cancer

Wang, Sen; Zhang, Xing; Li, Zheng; Wang, Weizhi; Li, Bowen; Huang, Xiaoxu; Sun, Guangli; Xu, Jianghao; Li, Qing; Xu, Zhipeng; Xia, Yiwen; Wang, Lu; Zhang, Qiang; Li, Qiang; Zhang, Lu; Chen, Jie; Wu, Yangjun; Cao, Jiacheng; Xu, Penghui; Zhang, Diancai; Xu, Hao; Xu, Zekuan

doi:10.1038/s41388-019-0933-0

Cited by 81 publications

(56 citation statements)

References 61 publications

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“…Dozens of circRNAs have been announced to participate in the progression of GC cells. For example, the novel circ_0000144, circOSBPL10 and circHECTD1 were upregulated in GC, and silencing of them could inhibit human GC cell proliferation, migration and invasion in vitro and in vivo [16][17][18]. The other tumor-related physiological processes had also been modulated by dysregulation of circRNAs, such as cell apoptosis, autophagy, Warburg effect, glutaminolysis, EMT, and cisplatin resistance, as well as the underlying signaling pathways [18][19][20][21].…”

Section: Discussionmentioning

confidence: 99%

Circ_0032821 acts as an oncogene in cell proliferation, metastasis and autophagy in human gastric cancer cells in vitro and in vivo through activating MEK1/ERK1/2 signaling pathway

et al. 2020

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Background: Circular RNA (circRNA) is increasingly attracting attention in gastric cancer (GC). Hsa_circ_0032821 (circ_0032821) has been declared to be upregulated in human GC tissues. However, the biological role of circ_0032821 remains undisclosed in GC cells. Methods: Expression of circ_0032821 was measured by real-time quantitative PCR. Cell proliferation, autophagy, Epithelial-mesenchymal transition (EMT), migration, and invasion were evaluated by Cell counting kit-8 assay, western blotting or transwell assays. Expression of proliferating cell nuclear antigen (PCNA), Matrix metalloproteinase 2 (MMP2), MMP9, Light chain 3 (LC3), p62, total and phosphorylated Extracellular signal-regulated kinase 1/2 (ERK1/2) and Mitogen-activated protein kinase's kinase 1 (MEK1) was evaluated by western blotting. Xenograft tumor model was established to measure tumor growth in vivo. Results: Circ_0032821 was significantly upregulated in human GC tumors and cells. Moreover, circ_0032821 might be a biomarker for the advanced Tumor node metastasis (TNM) stage, lymphoid node metastasis and poor prognosis in gastric cancer. Knockdown of circ_0032821 by transfection induced decrease of cell proliferation, EMT, migration and invasion, but increase of autophagy of AGS and HGC-27 cells in vitro, as well as induced tumor growth inhibition in vivo. Besides, overexpression of circ_0032821 by transfection functioned the opposite effects in human GC cells. Mechanically, the MEK1/ERK1/2 signaling pathway was activated when circ_0032821 upregulation, whereas inhibited when circ_0032821 silencing. Conclusion: Circ_0032821 expression induced cell proliferation, EMT, migration, invasion, and autophagy inhibition in human GC cells in vitro and in vivo through activating MEK1/ERK1/2 signaling pathway, suggesting circ_0032821 as an oncogenic role in GC.

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Section: Discussionmentioning

confidence: 99%

Circ_0032821 acts as an oncogene in cell proliferation, metastasis and autophagy in human gastric cancer cells in vitro and in vivo through activating MEK1/ERK1/2 signaling pathway

et al. 2020

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“…Advances in RNA sequencing technologies have accelerated the identification of circRNAs. CircRNAs are abundant and conserved RNA isoforms that are more stable than linear RNAs [7,8]. Divergent primers (primers in a primer pair that face away from each other) that cross over back-splicing sites have been used to amplify particular circular transcripts [9].…”

Section: Introductionmentioning

confidence: 99%

Circular RNA hsa_circ_0000326 acts as a miR-338-3p sponge to facilitate lung adenocarcinoma progression

Huang

et al. 2020

J Exp Clin Cancer Res

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Background: Circular RNAs (circRNAs) are a novel class of noncoding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. According to recent studies, circRNAs are involved in the pathogenesis of cancer, but the roles of circRNAs in lung adenocarcinoma are largely unknown. Methods: In this study, we identified a novel upregulated circRNA, hsa_circ_0000326, in human lung adenocarcinoma tissues using microarray analysis and qRT-PCR. We then explored the biological role of hsa_circ_0000326 using gainand loss-of-function assays in adenocarcinoma cells. Bioinformatics databases were used to screen for potential target miRNAs and the luciferase reporter assays and RNA-FISH further validated the interaction. Downstream protein was detected by western blot. Finally, we established xenografts in nude mice to assess the function of hsa_circ_0000326 in vivo. Results: We found that high expression of hsa_circ_0000326 was correlated with tumor size, regional lymph node status and differentiation in human lung adenocarcinoma. Additionally, we conducted gain-and loss-of-function assays and found that hsa_circ_0000326 acted as a positive regulator of cell proliferation and migration and a negative regulator of apoptosis. Mechanistic studies showed that hsa_circ_0000326 acted as a miR-338-3p sponge and altered the function of miR-338-3p, which in turn upregulated the expression of the downstream target RAB14 and affected the proliferation, migration and apoptosis of lung adenocarcinoma cells. Conclusions: Collectively, our study results reveal crucial roles for hsa_circ_0000326 in the proliferation, migration and apoptosis of lung adenocarcinoma cells and suggest that hsa_circ_0000326 may represent a potential therapeutic target in patients with lung adenocarcinoma.

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“…For instance, the expression of circOSBPL10 is upregulated in GC tissues and its level is a prognostic marker of the overall survival and disease-free survival of patients with GC. CircOSBPL10 promotes the growth and metastasis of gastric cancer by regulating miR-136-5p-WNT2 axis [38]. The expression of circAKT3 is higher in cisplatin (CDDP)-resistant GC tissues and cells than that in CDDP-sensitive samples.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA CCDC66 promotes gastric cancer progression by regulating c-Myc and TGF-β signaling pathways

Chen²,

Fu³

et al. 2020

J. Cancer

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Background: CircRNAs play important roles in cancer development and progression and have the potential to serve as cancer biomarkers. The aim of this study was to investigate the role of circular RNA CCDC66 (circCCDC66) in gastric cancer and to reveal the underlying mechanisms. Methods: The expression of circCCDC66 in GC tissues and cell lines was examined by qRT-PCR. The correlation between circCCDC66 expression level and clinicopathological characteristics was analyzed. The biological roles of circCCDC66 in GC cell apoptosis, proliferation, migration and invasion were determined by flow cytometry, cell counting, cell colony formation, wound healing, transwell migration and matrigel invasion assays. The role of circCCDC66 in GC growth was further confirmed by mouse xenograft tumor model. Western blot and qRT-PCR were used to explore the effects of circCCDC66 on epithelial-mesenchymal transition (EMT)-related gene and protein expression. Results: CircCCDC66 expression was elevated in both GC tissues and cell lines compared to adjacent normal tissues and normal gastric epithelial cell line. The upregulation of circCCDC66 in GC tissues was related to tumor stage and lymphatic metastasis. CircCCDC66 knockdown significantly inhibited GC cell proliferation, migration and invasion and induced cell apoptosis in GC cells. On the contrary, circCCDC66 overexpression had the opposite effects. In addition, circCCDC66 knockdown suppressed the tumorigenesis of GC cells in nude mice. Furthermore, circCCDC66 knockdown inhibited the activation of c-Myc and TGF-β signaling pathways and reversed EMT in GC cells. c-Myc and TGF-β interference blocked circCCDC66-mediated promotion of gastric cancer cell proliferation, migration and invasion. Conclusion: CircCCDC66 promotes GC growth and metastasis by activating c-Myc and TGF-β signaling pathways, suggesting that it may serve as a potential biomarker for GC.

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Circular RNA profile identifies circOSBPL10 as an oncogenic factor and prognostic marker in gastric cancer

Cited by 81 publications

References 61 publications

Circ_0032821 acts as an oncogene in cell proliferation, metastasis and autophagy in human gastric cancer cells in vitro and in vivo through activating MEK1/ERK1/2 signaling pathway

Circ_0032821 acts as an oncogene in cell proliferation, metastasis and autophagy in human gastric cancer cells in vitro and in vivo through activating MEK1/ERK1/2 signaling pathway

Circular RNA hsa_circ_0000326 acts as a miR-338-3p sponge to facilitate lung adenocarcinoma progression

Circular RNA CCDC66 promotes gastric cancer progression by regulating c-Myc and TGF-β signaling pathways

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