scholarly journals The novel role of circular RNA ST3GAL6 on blocking gastric cancer malignant behaviors through autophagy regulated by the FOXP2/MET/mTOR axis

2021 ◽  
Author(s):  
Penghui Xu ◽  
Xing Zhang ◽  
Jiacheng Cao ◽  
Jing Yang ◽  
Zetian Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Circular Rna ◽  
Circular Rnas ◽  
The Novel ◽  
Transcriptional Inhibition ◽  
And Migration ◽  
Induced Apoptosis

Abstract Gastric cancer (GC) ranks third in motality among all cancers worldwide. Circular RNAs (circRNAs) play essential roles in the malignant progression and metastasis of gastric cancer. As a transcription factor, FOXP2 is involved in the progression of many tumours. However, the regulation and association between circRNAs and FOXP2 remain to be discovered. In our study, CircST3GAL6 was significantly depressed in GC tissues and cells. circST3GAL6 overexpression inhibited the proliferation, invasion and metastasis of GC cells in vitro and in vivo. Importantly, circST3GAL6 overexpression induced apoptosis and promote autophagy in GC cells. Furthermore, we found that circST3GAL6 sponged miR-300 and subsequently regulated FOXP2. We further revealed that FOXP2 suppressed the activation of the Met/AKT/mTOR axis, a classic pathway that regulates autophagy-mediated proliferation and migration. In summary, our findings revealed that circST3GAL6 functions as a tumour suppressor through the miR-300/FOXP2 axis in GC, regulates apoptosis and autophagy through FOXP2-mediated transcriptional inhibition of the MET axis and may be a biomarker for GC treatment.

scholarly journals The Novel Role of Circular RNA ST3GAL6 on Blocking GC Malignant Behaviors Through Autophagy Regulated by the FOXP2/MET/Mtor Axis

2021 ◽  
Author(s):  
Penghui Xu ◽  
Xing Zhang ◽  
Jiacheng Cao ◽  
Jing Yang ◽  
Zetian Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Circular Rna ◽  
Circular Rnas ◽  
The Novel ◽  
Transcriptional Inhibition ◽  
And Migration ◽  
Induced Apoptosis

Abstract Gastric cancer (GC) ranks third in motality among all cancers worldwide. Circular RNAs (circRNAs) play essential roles in the malignant progression and metastasis of gastric cancer. As a transcription factor, FOXP2 is involved in the progression of many tumours. However, the regulation and association between circRNAs and FOXP2 remain to be discovered. In our study, CircST3GAL6 was significantly depressed in GC tissues and cells. circST3GAL6 overexpression inhibited the proliferation, invasion and metastasis of GC cells in vitro and in vivo. Importantly, circST3GAL6 overexpression induced apoptosis and promote autophagy in GC cells. Furthermore, we found that circST3GAL6 sponged miR-300 and subsequently regulated FOXP2. We further revealed that FOXP2 suppressed the activation of the Met/AKT/mTOR axis, a classic pathway that regulates autophagy-mediated proliferation and migration. In summary, our findings revealed that circST3GAL6 functions as a tumour suppressor through the miR-300/FOXP2 axis in GC, regulates apoptosis and autophagy through FOXP2-mediated transcriptional inhibition of the MET axis and may be a biomarker for GC treatment.

The Therapeutic Effect of Circular RNA ST3GAL6 on Blocking GC Malignant Behaviors Through Autophagy Regulated by the FOXP2/MET/Mtor Axis

2021 ◽  
Author(s):  
Penghui Xu ◽  
Xing Zhang ◽  
Jiacheng Cao ◽  
Jing Yang ◽  
Zetian Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Induced Apoptosis

Abstract Background: Gastric cancer (GC) ranks third in motality among all cancers worldwide. Circular RNAs (circRNAs) play essential roles in the malignant progression and metastasis of gastric cancer. As a transcription factor, FOXP2 is involved in the progression of many tumours. However, the regulation and association between circRNAs and FOXP2 remain to be discovered. Methods: RNA sequencing was used to explore differential circRNA expression profile in gastric cancer and quantitative real-time PCR (qRT-PCR) were used to detect circST3GAL6 expression. The cellular location of circST3GAL6 was determined by fluorescence in situ hybridization (FISH). Functional experiments in circST3GAL6 knockdown and overexpression cell lines were performed in vitro and in vivo. The correlation between circST3GAL6 and miR-300 was confirmed by the RNA pull-down assay, dual-luciferase reporter assay and fluorescence in situ hybridization (FISH). The effects of circST3GAL6 on autophagy were detected by confocal microscopy and transmission electron microscopy (TEM). The mechanism of the circST3GAL6/miR-300/FOXP2 axis was verified by western blotting. The transcriptional regulation of Met by FOXP2 was proven by ChIP and luciferase reporter assays.Results: CircST3GAL6 was significantly depressed in GC tissues and cells. circST3GAL6 overexpression inhibited the proliferation, invasion and metastasis of GC cells in vitro and in vivo. Importantly, circST3GAL6 overexpression induced apoptosis and promote autophagy in GC cells. Furthermore, we found that circST3GAL6 sponged miR-300 and subsequently regulated FOXP2. We further revealed that FOXP2 suppressed the activation of the Met/AKT/mTOR axis, a classic pathway that regulates autophagy-mediated proliferation and migration.Conclusion: Our findings revealed that circST3GAL6 functions as a tumour suppressor through the miR-300/FOXP2 axis in GC, regulates apoptosis and autophagy through FOXP2-mediated transcriptional inhibition of the MET axis and may be a biomarker for GC treatment.

scholarly journals Knockdown of Kremen2 Inhibits Tumor Growth and Migration in Gastric Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Beibei Chen ◽  
Sai-Qi Wang ◽  
Jinxi Huang ◽  
Weifeng Xu ◽  
Huifang Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Gastric Cancer Cells ◽  
And Migration ◽  
Induced Apoptosis ◽  
Gastric Cancer Patients

Kremen2 (Krm2) plays an important role in embryonic development, bone formation, and tumorigenesis as a crucial regulator of classical Wnt/β-catenin signaling pathway. However, the role of Krm2 in gastric cancer is not clear. The aim of this study was to explore the regulatory role of Krm2 in the tumorigenesis and metastasis of gastric cancer. It was demonstrated that, compared to para-cancerous tissues, Krm2 was significantly up-regulated in gastric cancer tissues and was positively correlated with the pathological grade of gastric cancer patients. Given that Krm2 is abundantly expressed in most tested gastric cancer cell lines, Krm2 knockdown cell models were established and further used to construct mice xenograft model. After knocking down Krm2, both the cell survival in vitro and tumorigenesis in vivo of gastric cancer cells were inhibited. At the same time, knockdown of Krm2 induced apoptosis, cell cycle arrest at G2/M phase and repression of migration in gastric cancer cells in vitro. Mechanistically, we found that knockdown of Krm2 suppressed PI3K/Akt pathway. Therefore, we revealed the novel role and the molecular mechanism of Krm2 in promoting the tumorigenesis and metastasis in gastric cancer. Krm2 can be a potent candidate for designing of targeted therapy.

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

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.

scholarly journals Circular RNA UBE2Q2 promotes malignant progression of gastric cancer by regulating signal transducer and activator of transcription 3-mediated autophagy and glycolysis

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Jing Yang ◽  
Xing Zhang ◽  
Jiacheng Cao ◽  
Penghui Xu ◽  
Zetian Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Rna Binding ◽  
Synergistic Effects ◽  
Circular Rna ◽  
Circular Rnas ◽  
In Vivo Experiments ◽  
Series Of Experiments ◽  
Transcription 3

AbstractGastric cancer remains the third leading cause of cancer-related mortality worldwide. Emerging evidence has shown that circular RNAs (circRNAs) play a critical regulatory role in the occurrence and development of various cancers through sponging miRNAs or acting as RNA-binding protein (RBP) sponges. We found that circUBE2Q2 was significantly upregulated in GC tissues and cell lines. Knockdown of circUBE2Q2 inhibited proliferation, migration, invasion, and glycolysis, and increased autophagy in vitro. In addition, knockdown of circUBE2Q2 inhibited GC tumorigenicity and metastasis potential in vivo. A series of experiments were performed to confirm that circUBE2Q2 regulates GC progression via the circUBE2Q2-miR-370-3p-STAT3 axis and promotes tumor metastasis through exosomal communication. Further in vivo experiments confirmed that, combination treatment of circUBE2Q2 knocking down and STAT3 inhibitor has synergistic effects on the gastric cancer growth inhibition, which provides a possibility to enhance the sensitivity of targeted drugs to gastric cancer through targeting circUBE2Q2. Our findings revealed that circUBE2Q2 may serve as a new proliferation-promoting factor and prognostic marker in gastric cancer.

scholarly journals Circular RNA MCTP2 inhibits cisplatin resistance in gastric cancer by miR-99a-5p-mediated induction of MTMR3 expression

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Guangli Sun ◽  
Zheng Li ◽  
Zhongyuan He ◽  
Weizhi Wang ◽  
Sen Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Xenograft Model ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Mouse Xenograft Model ◽  
Mirna Sponges ◽  
High Level

Abstract Background Cisplatin (CDDP) is the first-line chemotherapy for gastric cancer (GC). The poor prognosis of GC patients is partially due to the development of CDDP resistance. Circular RNAs (circRNAs) are a subclass of noncoding RNAs that function as microRNA (miRNA) sponges. The role of circRNAs in CDDP resistance in GC has not been evaluated. Methods RNA sequencing was used to identify the differentially expressed circRNAs between CDDP-resistant and CDDP-sensitive GC cells. qRT-PCR was used to detect the expression of circMCTP2 in GC tissues. The effects of circMCTP2 on CDDP resistance were investigated in vitro and in vivo. Pull-down assays and luciferase reporter assays were performed to confirm the interactions among circMCTP2, miR-99a-5p, and myotubularin-related protein 3 (MTMR3). The protein expression levels of MTMR3 were detected by western blotting. Autophagy was evaluated by confocal microscopy and transmission electron microscopy (TEM). Results CircMCTP2 was downregulated in CDDP-resistant GC cells and tissues compared to CDDP-sensitive GC cells and tissues. A high level of circMCTP2 was found to be a favorable factor for the prognosis of patients with GC. CircMCTP2 inhibited proliferation while promoting apoptosis of CDDP-resistant GC cells in response to CDDP treatment. CircMCTP2 was also found to reduce autophagy in CDDP-resistant GC cells. MiR-99a-5p was verified to be sponged by circMCTP2. Inhibition of miR-99a-5p could sensitize GC cells to CDDP. MTMR3 was confirmed to be a direct target of miR-99a-5p. Knockdown of MTMR3 reversed the effects of circMCTP2 on the proliferation, apoptosis and autophagy of CDDP-resistant GC cells. CircMCTP2 was also confirmed to inhibit CDDP resistance in vivo in a nude mouse xenograft model. Conclusions CircMCTP2 sensitizes GC to CDDP through the upregulation of MTMR3 by sponging miR-99a-5p. Overexpression of CircMCTP2 could be a new therapeutic strategy for counteracting CDDP resistance in GC.

scholarly journals Circular RNA circRPPH1 promotes breast cancer progression via circRPPH1-miR-512-5p-STAT1 axis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yixiang Huang ◽  
Wenfang Zheng ◽  
Changle Ji ◽  
Xuehui Wang ◽  
Yunhe Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Underlying Mechanism ◽  
Circular Rna ◽  
Gene Expression Omnibus ◽  
Circular Rnas ◽  
In Vivo Experiments

AbstractBreast cancer (BC) is one of the most fatal diseases among women all over the world. Non-coding RNAs including circular RNAs (circRNAs) have been reported to be involved in different aspects during tumorigenesis and progression. In this study, we aimed to explore the biological functions and underlying mechanism of circRPPH1 in BC. Candidate circRNAs were screened in dataset GSE101123 from Gene Expression Omnibus (GEO) database and a differentially expressed circRNA, circRPPH1, was discovered in BC. CircRPPH1 expression was higher in the cancerous tissue compared to paired adjacent tissue. Further in vitro and in vivo experiments indicated that circRPPH1 acted as an oncogene in BC. In addition, circRPPH1 was mainly localized in cytoplasm and played the role of miR-512-5p sponge. By sequestering miR-512-5p from the 3′-UTR of STAT1, circRPPH1 inhibited the suppressive role of miR-512-5p, stabilized STAT1 mRNA in BC and finally affected BC progression. In conclusion, these findings indicated that circRPPH1 acted as an oncogene and regulated BC progression via circRPPH1-miR-512-5p-STAT1 axis, which might provide a potential therapeutic target for BC treatment.

scholarly journals Circular RNA circASPM Promotes the Progression of Glioblastoma by Acting as a Competing Endogenous RNA to Regulate miR-130b–3p/E2F1 Axis

2020 ◽  
Author(s):  
Dianqi Hou ◽  
Zhenlin Wang ◽  
Haimeng Li ◽  
Juan Liu ◽  
Yaohua Liu ◽  
...  
Keyword(s):  
Western Blotting ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Primary Malignancy ◽  
Rna Immunoprecipitation ◽  
Western Blotting Assay

Abstract background: Glioblastoma Multiform (GBM) is the primary malignancy with the highest incidence and worst prognosis in the adult CNS. Circular RNAs (circRNAs) are a novel and widely diverse class of endogenous non-coding RNAs that can promote or inhibit gliomagenesis. Our study aimed to explore the role of circASPM in GBM and its molecular mechanism.Methods: Levels of circASPM, miR-130b-3p and E2F1 were determined by quantitative real-time PCR (qRT-PCR) or western blotting assay. MTS, Edu, neurospheres formation and extreme limiting dilution assays were used to detect the tumorigenesis and proliferation of GSCs in vitro. The interactions between miR-130b-3p and circASPM or E2F1 was demonstrated via qPCR, western blotting, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft experiments was used to analyze tumor growth in vivo.Results: CircASPM was overexpressed in GBM and could promote the tumorigenesis and proliferation of GSCs both in vitro and in vivo. Mechanistically, circASPM up-regulated the expression of E2F1 in GSCs via miR-130b-3p sponging. We furtherly demonstrated that circAPSM could promote the GSCs proliferation via E2F1 up-regulating. Therefore, our study identified a novel circRNA and its possible mechanism in the development and tumorigenesis of GBM.Conclusions: CircASPM can promote GBM progression via regulating miR-130b-3p/E2F1 axis, suggesting that circAPSM could provide an effective biomarker for GBM diagnosis and prognostic evaluation and possibly being used for molecular targeted therapy.

scholarly journals Circular RNA circ_001621 promotes osteosarcoma cells proliferation and migration by sponging miR-578 and regulating VEGF expression

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xianglu Ji ◽  
Liping Shan ◽  
Peng Shen ◽  
Ming He
Keyword(s):  
Experimental System ◽  
Circular Rna ◽  
Circular Rnas ◽  
Micro Rnas ◽  
And Migration ◽  
Set Up ◽  
Endothelial Growth Factor ◽  
Proliferation And Migration

AbstractStrategies targeted vascular endothelial growth factor (VEGF)-dependent osteosarcoma progression are limited although important progress has been made in illustrating the mechanisms. Here we identified circ_001621 as one of the significantly upregulated circular RNAs (circRNAs) by circRNAs microarrays. We found that patients with high circ_001621 expression had a shorter survival time. Moreover, we found several potential sponge micro RNAs (miRNA) of circ_001621 with Circular RNA Interactome database. Among the candidate sponge, we elucidated the association of circ_001621 and miR-578. In addition, we demonstrated that miR-578 targeted circ_001621 directly. Functionally, we set up the experimental system to investigate the effects of circ_001621/miR-578/VEGF interaction in vitro and in vivo. Results indicated circ_001621-promoted osteosarcoma proliferation and migration via attenuating the inhibition of cyclin-dependent kinase 4 (CDK4) and matrix metallopeptidase 9 (MMP9) by miR-578, respectively. Nude mice experiment was further performed to estimate the promotion of metastasis by circ_001621. The present study evaluated the mechanisms underlying circ_001621 enhanced osteosarcoma progression and provided novel therapeutic targets for advanced osteosarcoma.

scholarly journals Novel circular RNA circSLIT2 facilitates the aerobic glycolysis of pancreatic ductal adenocarcinoma via miR-510-5p/c-Myc/LDHA axis

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Hua Guan ◽  
Wei Luo ◽  
Yuping Liu ◽  
Mingfei Li
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Aerobic Glycolysis ◽  
Circular Rna ◽  
Ductal Adenocarcinoma ◽  
Circular Rnas ◽  
The Novel ◽  
Mirna Sponge ◽  
Promising Therapeutic Target

AbstractIncreasing evidence has indicated the great diagnostic and therapeutic potentials of circular RNAs (circRNAs) in human cancers. Although the biological roles of circRNAs in pancreatic ductal adenocarcinoma (PDAC) have been partially annotated, the potential regulatory mechanism of circRNAs in PDAC tumorigenesis remains poorly understood. Here, our study found that the novel circRNA circSLIT2 was significantly upregulated in PDAC tissues and cells. Clinically, ectopic high-expression of circSLIT2 was correlated with unfavorable prognosis of PDAC patients. Functional experiments demonstrated that circSLIT2 promoted the aerobic glycolysis and proliferation of PDAC cells in vitro, and circSLIT2 knockdown inhibited tumor growth in vivo. Mechanistically, circSLIT2 acted as miRNA sponge to target miR-510-5p/c-Myc axis. Furthermore, c-Myc bound with the promoter region of lactate dehydrogenase A (LDHA) to activate the transcription. Collectively, present findings reveal that circSLIT2/miR-510-5p/c-Myc/LDHA axis participates in the aerobic glycolysis and carcinogenesis of PDAC, and may act as a promising therapeutic target.

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