Circular RNA 0047905 acts as a sponge for microRNA4516 and microRNA1227-5p, initiating gastric cancer progression.
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ABSTRACT:
SUBMITTER: Lai Z
PROVIDER: S-EPMC6619930 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
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Circular RNA 0047905 acts as a sponge for microRNA4516 and microRNA1227-5p, initiating gastric cancer progression.
Lai Zhiyong Z Yang Yang Y Wang Chaobing C Yang Wenhui W Yan Yichao Y Wang Zhu Z Xu Jun J Jiang Kewei K
Cell cycle (Georgetown, Tex.) 20190604 14
Several lines of evidence suggest that circular RNAs (circRNAs) play important roles in oncogenesis and tumor progression. However, our knowledge of the role of circRNAs in gastric cancer (GC) remains limited. We investigated the possibility that circular RNA 0047905 (circRNA0047905) might act as a tumor promoter in the pathogenesis of gastric cancer by profiling miRNA expression in GC tissues and paired noncancerous mucosa tissues using miRNA microarrays. Next, a ceRNA network was constructed a ...[more]
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Project description:BackgroundAccumulating evidences have shown that circular RNAs (circRNAs) play important roles in regulating the pathogenesis of cancer. However, the role of circRNAs in gastric cancer (GC) remains largely unclear.MethodsIn this study, we identified a novel upregulated circRNA, hsa_circ_0001829, in chemically induced malignant transformed human gastric epithelial cells using RNA-seq. Subsequent qRT-PCR and ISH assays were performed to detect the expression level of hsa_circ_0001829 in GC cell lines and tissues. Functional roles of hsa_circ_0001829 in GC were then explored by loss- and gain-of- function assays. Bioinformatic prediction and luciferase assay were used to investigate potential mechanisms of hsa_circ_0001829. Finally, the mice xenograft and metastasis models were constructed to assess the function of hsa_circ_0001829 in vivo.ResultsWe found that hsa_circ_0001829 was significantly upregulated in GC tissues and cell lines. Loss- and gain-of- function assays showed that hsa_circ_0001829 promotes GC cells proliferation, migration and invasion, and the affected cell cycle progression and apoptosis rates may account for the effect of hsa_circ_0001829 on GC proliferation. In addition, bioinformatic prediction and luciferase assay showed that hsa_circ_0001829 acts as a molecular sponge for miR-155-5p and that SMAD2 was a target gene of miR-155-5p; moreover, hsa_circ_0001829 sponges miR-155-5p to regulate SMAD2 expression and hsa_circ_0001829 promotes GC progression through the miR-155-5p-SMAD2 pathway. Finally, suppression of hsa_circ_0001829 expression inhibited tumor growth and aggressiveness in vivo.ConclusionTaken together, our findings firstly demonstrated a novel oncogenic role of hsa_circ_0001829 in GC progression through miR-155-5p-SMAD2 axis, and our study may offer novel biomarkers and therapeutic targets for GC.
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Project description:Background:The antisense cerebellar degenerative-related protein-1 (CDR1as) has been identified as a sponge for several microRNAs. MiR-641 has been shown to be downregulated in osteoarthritic human chondrocytes, but its regulation and function in osteoarthritis (OA) has not been reported. Methods:OA cartilage samples were obtained from the knee joints of 12 patients (8 males and 4 females at age of 57-73?years old) who underwent total knee arthroplasty. Normal articular cartilage samples were obtained from the knee joints of 10 trauma patients at age of 29-65?years old (6 males and 4 females). The levels of circRNA-CDR1as mRNA and miR-641 were examined by qRT-PCR and the contents of type II collagen (Col II), IL-6, MMP13 and GAPDH in chondrocytes were examined by Western blot. Results:In this study, we found that circRNA-CDR1as level was significantly upregulated in OA chondrocytes, and negatively related with that of miR-641. RNA pull down assay confirmed that circRNA-CDR1as directly targets to miR-641. Furthermore, downregulation of circRNA-CDR1as increased type II collagen level but reduced MMP13 and IL-6 contents, while these effects were partly reversed by down-regulation of miR-641. Conclusion:Overall, our results indicate that circRNA-CDR1as plays a crucial role in regulating OA progression via modulating extracellular matrix metabolism and inflammation via sponging miR-641 and provide a novel regulatory role of circRNA-CDR1as in OA.
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Project description:BackgroundCircular RNA (circRNA) represents a broad and diverse endogenous RNAs that can regulate gene expression in cancer. However, the regulation and function of bladder cancer (BC) circRNAs remain largely unknown.MethodsHere we generated circRNA microarray data from three BC tissues and paired non-cancerous matched tissues, and detected circular RNA-cTFRC up-regulated and correlated with tumor grade and poor survival rate of BC patients. We subsequently performed functional analyses in cell lines and an animal model to support clinical findings. Mechanistically, we demonstrated that cTFRC could directly bind to miR-107 and relieve suppression for target TFRC expression.ResultsWe detected circular RNA-cTFRC up-regulated and correlated with tumor grade and poor survival rate of BC patients. Knock down of cTFRC inhibited invasion and proliferation of BC cell lines in vitro and tumor growth in vivo. Furthermore, the expression of cTFRC correlated with TFRC and negatively correlated with miR-107 both in BC cell lines and BC clinical samples. In addition, up-regulation of cTFRC promoted TFRC expression and contributed to an epithelial to mesenchymal transition phenotype in BC cells. Finally, we found that cTFRC acts as a competing endogenous RNA (ceRNA) for miR-107 to regulate TFRC expression.ConclusionscTFRC may exert regulatory functions in BC and may be a potential marker of BC diagnosis or progression.
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