Circular RNA _0008278 acts as a sponge of miR-378 and promotes proliferation and metastasis in gastric cancer

Abstract Background: Circular RNA (circRNA) is rising as an indispensable regulatory molecule in the progression of various kinds of malignant growth. However, little is known about the capacity and instruments of circRNA_0008727 in gastric cancer (GC). Our point was to recognize a novel circRNA-microRNA-mRNA useful system in gastric cancer. Method: CircRNA_0008278 was identified in three paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circRNA_0008278 combined with in vitro and in vivo assays were performed to prove the functional significance of circRNA_0008278. The molecular mechanism of circRNA_0008278 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments.Results: CircRNA_0008278 was frequently upregulated in GC tissues, and high circRNA_0008278 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circRNA_0008278 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, circRNA_0008278 over-expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circRNA_0008278 could sponge miR-378, thus indirectly regulating theYY1 expression and contributing to GC tumourigenesis.Conclusion: Our findings demonstrate that circRNA_0008278 functions as a tumour promoter in GC, and a new pathway circRNA_0008278/miR-378/YY1 which may be potential method for gastric cancer treatment.

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circLMTK2 acts as a sponge of miR-150-5p and promotes proliferation and metastasis in gastric cancer

Molecular Cancer ◽

10.1186/s12943-019-1081-4 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 15

Author(s):

Sen Wang ◽

Dong Tang ◽

Wei Wang ◽

Yining Yang ◽

Xiaoqing Wu ◽

...

Keyword(s):

Gastric Cancer ◽

Bioinformatic Analysis ◽

Migration And Invasion ◽

Circular Rnas ◽

Normal Tissues ◽

Tumour Metastasis ◽

Genome Wide ◽

Proliferation And Metastasis

Abstract Background As a novel class of non-coding RNAs, circular RNAs (circRNAs) are key regulators of the development and progression of different cancers. However, little is known about the function and biological mechanism of circLMTK2, also named hsa_circ_0001725, in gastric cancer (GC) tumourigenesis. Methods circLMTK2 was identified in ten paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circLMTK2 combined with in vitro and in vivo assays were performed to prove the functional significance of circLMTK2. The molecular mechanism of circLMTK2 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments. Results circLMTK2 was frequently upregulated in GC tissues, and high circLMTK2 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circLMTK2 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, ectopic circLMTK2 expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circLMTK2 could sponge miR-150-5p, thus indirectly regulating the c-Myc expression and contributing to GC tumourigenesis. Conclusion Our findings demonstrate that circLMTK2 functions as a tumour promoter in GC through the miR-150-5p/c-Myc axis and could thus be a prognostic predictor and therapeutic target for GC.

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Circular RNA CDR1as Inhibits the Metastasis of Gastric Cancer through Targeting miR-876-5p/GNG7 Axis

Gastroenterology Research and Practice ◽

10.1155/2021/5583029 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Jiajia Jiang ◽

Rong Li ◽

Junyi Wang ◽

Jie Hou ◽

Hui Qian ◽

...

Keyword(s):

Gastric Cancer ◽

Epithelial Mesenchymal Transition ◽

Circular Rna ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Luciferase Reporter Gene ◽

Mesenchymal Transition ◽

Underlying Mechanisms

Circular RNA CDR1as has been demonstrated to participate in various cancer progressions as miRNA sponges. The exact underlying mechanisms of CDR1as on gastric cancer (GC) metastasis remain unknown. Here, we found that CDR1as knockdown facilitated GC cell migration and invasion while its overexpression inhibited the migration and invasion abilities of GC cells in vitro and in vivo. Moreover, epithelial-mesenchymal transition- (EMT-) associated proteins and MMP2 and MMP9 were downregulated by CDR1as. Bioinformatics analysis combined with dual-luciferase reporter gene assays, western blot, RT-qPCR analysis, and functional rescue experiments demonstrated that CDR1as served as a miR-876-5p sponge and upregulated the target gene GNG7 expression to suppress GC metastasis. In summary, our findings indicate that CDR1as suppresses GC metastasis through the CDR1as/miR-876-5p/GNG7 axis.

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Inhibition of circRNA circVPS33B reduces cell malignant behaviors and Warburg effect through regulation of the miR-873-5p/HNRNPK axis in infiltrative gastric cancer

10.21203/rs.3.rs-43509/v1 ◽

2020 ◽

Author(s):

Yizhuo Lu ◽

Jia Cheng ◽

Wangyu Cai ◽

Huiqin Zhuo ◽

Guoyang Wu ◽

...

Keyword(s):

Gastric Cancer ◽

Colony Formation ◽

Warburg Effect ◽

Lactate Production ◽

Circular Rna ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Inhibitory Influence

Abstract Background Circular RNA VPS33B (circVPS33B) is upregulated in gastric cancer (GC) tissues. However, the role of circVPS33B in infiltrative GC is indistinct. Methods Expression of circVPS33B, miR-873-5p, and heterogeneous nuclear ribonucleoprotein K (HNRNPK) mRNA was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, colony formation, migration, and invasion of infiltrative GC cells (XGC-1) were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT), plate clone, wound healing, or transwell assays. Several protein levels were examined by western blotting. The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of XGC-1 cells were evaluated by XF96 extracellular flux analyzer. Glucose uptake and lactate production were analyzed by glycolysis assay. The relationship between circVPS33B or HNRNPK and miR-873-5p was verified by dual-luciferase reporter and/or RNA pull-down assays. In vivo tumorigenesis assay was executed for verifying the in vitro results. Results CircVPS33B and HNRNPK were upregulated while miR-873-5p was downregulated in infiltrative GC tissues and XGC-1 cells. CircVPS33B silencing decreased tumor growth in vivo and inhibited proliferation, colony formation, migration, invasion, and Warburg effect of XGC-1 cells in vitro. CircVPS33B regulated HNRNPK expression via sponging miR-873-5p. The inhibitory influence of circVPS33B knockdown on the malignancy and Warburg effect of XGC-1 cells was overturned by miR-873-5p inhibitor. HNRNPK overexpression reversed the repression of the malignancy and Warburg effect of XGC-1 cells caused by miR-873-5p mimic. Conclusions CircVPS33B accelerated infiltrative GC progression through regulating the miR-873-5p/HNRNPK axis, manifesting that circVPS33B might be a promising target for infiltrative GC treatment.

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Inhibition of circRNA circVPS33B reduces cell malignant behaviors and Warburg effect through regulation of the miR-873-5p/HNRNPK axis in infiltrative gastric cancer

10.21203/rs.3.rs-43509/v2 ◽

2020 ◽

Author(s):

Yizhuo Lu ◽

Jia Cheng ◽

Wangyu Cai ◽

Huiqin Zhuo ◽

Guoyang Wu ◽

...

Keyword(s):

Gastric Cancer ◽

Colony Formation ◽

Warburg Effect ◽

Lactate Production ◽

Circular Rna ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Inhibitory Influence

Abstract Background: Circular RNA VPS33B (circVPS33B) is upregulated in gastric cancer (GC) tissues. However, the role of circVPS33B in infiltrative GC is indistinct. Methods: Expression of circVPS33B, miR-873-5p, and heterogeneous nuclear ribonucleoprotein K (HNRNPK) mRNA was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, colony formation, migration, and invasion of infiltrative GC cells (XGC-1) were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT), plate clone, wound healing, or transwell assays. Several protein levels were examined by western blotting. The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of XGC-1 cells were evaluated by XF96 extracellular flux analyzer. Glucose uptake and lactate production were analyzed by glycolysis assay. The relationship between circVPS33B or HNRNPK and miR-873-5p was verified by dual-luciferase reporter and/or RNA pull-down assays. In vivo tumorigenesis assay was executed for verifying the in vitro results.Results: CircVPS33B and HNRNPK were upregulated while miR-873-5p was downregulated in infiltrative GC tissues and XGC-1 cells. CircVPS33B silencing decreased tumor growth in vivo and inhibited proliferation, colony formation, migration, invasion, and Warburg effect of XGC-1 cells in vitro. CircVPS33B regulated HNRNPK expression via sponging miR-873-5p. The inhibitory influence of circVPS33B knockdown on the malignancy and Warburg effect of XGC-1 cells was overturned by miR-873-5p inhibitor. HNRNPK overexpression reversed the repression of the malignancy and Warburg effect of XGC-1 cells caused by miR-873-5p mimic.Conclusions: CircVPS33B accelerated infiltrative GC progression through regulating the miR-873-5p/HNRNPK axis, manifesting that circVPS33B might be a promising target for infiltrative GC treatment.

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Circular RNA CDR1as Promotes Gastric Cancer Growth via miR-299-3p/TGIF1 Axis

10.21203/rs.3.rs-1081040/v1 ◽

2021 ◽

Author(s):

Rong Li ◽

Jiajia Jiang ◽

Junyi Wang ◽

Jie Hou ◽

Dongli Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Circular Rna ◽

Luciferase Reporter ◽

Healthy Controls ◽

Luciferase Reporter Gene ◽

Normal Tissues ◽

Analysis Survival ◽

Related Proteins

Abstract Background Gastric cancer (GC) is a common malignancy worldwide. Circular RNA CDR1as has been reported as a crucial regulator in human diseases including cancer. However, its biological roles, mechanisms and clinical values in GC remain largely unknown. Methods and Results CDR1as levels were surveyed in paired GC and adjacent normal tissues, paired blood samples from GC patients and healthy controls by RT-qPCR. Its clinical values were evaluated by ROC analysis, survival analysis and correlations with clinic pathological features. Cell transfection was performed to manipulate gene expression. In vitro CCK8 and colony formation assays and in vivo xenograft mouse model were employed to determine CDR1as effects on GC growth. CDR1as-miRNA and miRNA-mRNA interactions were predicted by bioinformatics analysis and further verified by RIP, dual-luciferase reporter gene assays, RT-qPCR, western blot and functional rescue experiments. Our results showed that CDR1as level was significantly downregulated in GC tissues and correlated with nerve invasion and poor prognosis. GC patients presented higher plasma CDR1as level than healthy controls. Functionally, knockdown of CDR1as inhibited GC cell proliferation and viability while its overexpression promoted GC growth in vitro and in vivo. The proliferation-related proteins PCNA and Cyclin D1 and apoptosis-related proteins Bax, Bcl-2, Caspase-3 and Caspase-9 were regulated. Mechanistically, CDR1as acted as a miR-299-3p sponge to relieve its suppressive effects and upregulate TGIF1 expression to promote GC growth.Conclusions CDR1as may be considered as a potential diagnostic and prognostic biomarker for GC. CDR1as/miR-299-3p/TGIF1 axis promotes GC growth in vitro and in vivo.

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Circular RNA Circ-0002570 Accelerates Cancer Progression by Regulating VCAN via MiR-587 in Gastric Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.733745 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lei Yang ◽

Yong-ning Zhou ◽

Miao-miao Zeng ◽

Nan Zhou ◽

Bin-sheng Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Progression ◽

Circular Rna ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

Functional Roles ◽

Reporter Assays

BackgroundCircular RNAs (circRNAs) are closely associated with the occurrences and progress of gastric cancer (GC). We aimed to delve into the function and pathological mechanism of Circular RNA-0002570 (circ-0002570) in GC progression.MethodsCircRNAs differentially expressed in GC were screened using bioinformatics technology. The expression of circ-0002570 was detected in GC specimens and cells via qRT-PCR, and the prognostic values of circ-0002570 were determined. The functional roles of circ-0002570 on proliferation, migration, and invasion in GC cells were explored in vitro and in vivo. Interaction of circ-0002570, miR-587, and VCAN was confirmed by dual-luciferase reporter assays, Western blotting, and rescue experiments.ResultsCirc-0002570 expression was distinctly increased in GC tissues compared to adjacent normal specimens, and GC patients with higher circ-0002570 expressions displayed a short survival. Functionally, knockdown of circ-0002570 resulted in the inhibition of cell proliferation, migration, and invasion, and suppressed tumor growth in vivo. Mechanistically, miR-587 was sponged by circ-0002570. VCAN expression in NSCLC was directly inhibited by miR-587. Overexpression of circ-0002570 prevented VCAN from miR-587-mediated degradation and thus facilitated GC progression.ConclusionThe circ-0002570-miR-587-VCAN regulatory pathway promoted the progression of GC. Our findings provided potential new targets for the diagnosis and therapy of GC.

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Circular RNA hsa_circ_0110389 promotes gastric cancer progression through upregulating SORT1 via sponging miR-127-5p and miR-136-5p

Cell Death and Disease ◽

10.1038/s41419-021-03903-5 ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Min Liang ◽

Wenxia Yao ◽

Boyun Shi ◽

Xiongjie Zhu ◽

Rui Cai ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Progression ◽

Circular Rna ◽

Migration And Invasion ◽

Circular Rnas ◽

Environmental Carcinogen ◽

Advanced Stages

AbstractIncreasing studies have found that circular RNAs (circRNAs) are aberrantly expressed and play important roles in the occurrence and development of human cancers. However, the function of circRNAs on environmental carcinogen-induced gastric cancer (GC) progression remains poorly elucidated. In the present study, hsa_circ_0110389 was identified as a novel upregulated circRNA in malignant-transformed GC cells through RNA-seq, and subsequent quantitative real-time PCR verified that hsa_circ_0110389 was significantly increased in GC tissues and cells. High hsa_circ_0110389 expression associates with advanced stages of GC and predicts poor prognosis. Knockdown and overexpression assays demonstrated that hsa_circ_0110389 regulates proliferation, migration, and invasion of GC cells in vitro. In addition, hsa_circ_0110389 was identified to sponge both miR-127-5p and miR-136-5p and SORT1 was validated as a direct target of miR-127-5p and miR-136-5p through multiple mechanism assays; moreover, hsa_circ_0110389 sponged miR-127-5p/miR-136-5p to upregulate SORT1 expression and hsa_circ_0110389 promoted GC progression through the miR-127-5p/miR-136-5p–SORT1 pathway. Finally, hsa_circ_0110389 knockdown suppressed GC growth in vivo. Taken together, our findings firstly identify the role of hsa_circ_0110389 in GC progression, which is through miR-127-5p/miR-136-5p–SORT1 pathway, and our study provides novel insight for the identification of diagnostic/prognostic biomarkers and therapeutic targets for GC.

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Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001364 ◽

2021 ◽

Vol 9 (2) ◽

pp. e001364

Author(s):

Yan Zhang ◽

Hui Yang ◽

Jun Zhao ◽

Ping Wan ◽

Ye Hu ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Metabolism ◽

Vital Role ◽

Methionine Metabolism ◽

Promoter Regions ◽

Normal Tissues ◽

Methionine Cycle

BackgroundThe activation of tumor-associated macrophages (TAMs) facilitates the progression of gastric cancer (GC). Cell metabolism reprogramming has been shown to play a vital role in the polarization of TAMs. However, the role of methionine metabolism in function of TAMs remains to be explored.MethodsMonocytes/macrophages were isolated from peripheral blood, tumor tissues or normal tissues from healthy donors or patients with GC. The role of methionine metabolism in the activation of TAMs was evaluated with both in vivo analyses and in vitro experiments. Pharmacological inhibition of the methionine cycle and modulation of key metabolic genes was employed, where molecular and biological analyses were performed.ResultsTAMs have increased methionine cycle activity that are mainly attributed to elevated methionine adenosyltransferase II alpha (MAT2A) levels. MAT2A modulates the activation and maintenance of the phenotype of TAMs and mediates the upregulation of RIP1 by increasing the histone H3K4 methylation (H3K4me3) at its promoter regions.ConclusionsOur data cast light on a novel mechanism by which methionine metabolism regulates the anti-inflammatory functions of monocytes in GC. MAT2A might be a potential therapeutic target for cancer cells as well as TAMs in GC.

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Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000478685 ◽

2017 ◽

Vol 42 (3) ◽

pp. 1025-1036 ◽

Cited By ~ 12

Author(s):

Dehu Chen ◽

Guiyuan Liu ◽

Ning Xu ◽

Xiaolan You ◽

Haihua Zhou ◽

...

Keyword(s):

Gastric Cancer ◽

Western Blot ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Invasion And Metastasis ◽

Ags Cells ◽

Mesenchymal Transition

Background/Aims: Gastric cancer (GC) is a common and lethal malignancy, and AMP-activated protein kinase-related kinase 5 (ARK5) has been discovered to promote cancer metastasis in certain types of cancer. In this study, we explored the role of ARK5 in GC invasion and metastasis. Methods: ARK5 and epithelial-mesenchymal transition (EMT)-related markers were determined by immunohistochemistry and western blot in GC specimens. Other methods including stably transfected against ARK5 into SGC7901 and AGS cells, western blot, migration and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. Results: The results demonstrated that ARK5 expression was increased and positively correlated with metastasis, EMT-related markers and poor prognosis in patients with GC. Knockdown of ARK5 expression remarkably suppressed GC cells invasion and metastasis via regulating EMT, rather than proliferation in vitro and in vivo. And knockdown of ARK5 expression in GC cells resulted in the down-regulation of the mTOR/p70S6k signals, Slug and SIP1. Conclusion: The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in GC cells migration and invasion via EMT alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1, thus providing a potential therapeutic target for GC.

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Circular RNA circFAT1(e2) Promotes Colorectal Cancer Tumorigenesis via the miR-30e-5p/ITGA6 Axis

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/9980459 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Fei Pan ◽

Dongqing Zhang ◽

Na Li ◽

Mei Liu

Keyword(s):

Colorectal Cancer ◽

Circular Rna ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

Small Interfering Rnas ◽

Regulatory Relationship ◽

Downstream Target ◽

Normal Tissues

circRNAs (circular RNAs) are a family of noncoding RNAs and have diverse physiological and pathological functions. However, the functions and mechanisms of circRNAs in the development and progression of colorectal cancer (CRC) remain largely unknown. Here, we aimed to explore the functions and roles of circFAT1(e2) in CRC. qRT-PCR revealed that circFAT1(e2) in CRC tumor tissues was upregulated compared with that in adjacent normal tissues and was also upregulated in CRC cell lines. Small interfering RNAs (siRNAs) against circFAT1(e2) were used to decrease the expression of circFAT1(e2) in HCT116 and RKO cells in vitro. The roles of circFAT1(e2) in CRC cell metastasis and proliferation were then determined by transwell and CCK-8 assays. The results showed that circFAT1(e2) silencing markedly suppressed CRC growth. Moreover, we identified circFAT1(e2) as a promoter of CRC metastasis. Knockdown of circFAT1(e2) evidently reduced HCT116 and RKO cell migration and invasion. Furthermore, the regulatory relationship between circFAT1(e2) and its target miRNAs was verified by a luciferase reporter assay. We demonstrated that circFAT1(e2) could sponge miR-30e-5p, which regulated the expression level of integrin α6 (ITGA6), the downstream target gene of miR-30e-5p. Rescue assays demonstrated that knockdown of miR-30e-5p enhanced CRC proliferation and migration via ITGA6. Taken together, our results reveal the novel oncogenic roles of circFAT1(e2) in CRC through the miR-30e-5p/ITGA6 axis.

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