Circular RNA hsa_circ_0001829 Promotes Gastric Cancer Progression through miR-155-5p/SMAD2 Axis

Abstract

Background: Accumulating 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. Methods: In 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 was 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 models were constructed to assess the function of hsa_circ_0001829 in vivo.Results: We 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 subcutaneous tumor growth in vivo. Conclusion: Taken together, our findings firstly demonstrated a novel oncogenic role of hsa_circ_0001829 in GC progression, which is through miR-155-5p–SMAD2 axis, and our study may offer novel biomarkers and therapeutic targets for GC.

Circular RNA circ_001422 Promotes Progression and Metastasis of Osteosarcoma via the miR-195-5p/FGF2/PI3K/Akt Axis

“…Unlike these two kinds of ncRNAs, circRNAs have emerged as more reliable and promising tumor biomarkers owing to their exceptionally stable structure. Advanced genome sequencing techniques have validated the roles of circRNAs in multiple cancer types including hepatocellular carcinoma [24], gastric cancer [25], colorectal cancer [26] and lung squamous carcinoma [27]. However, to date, the expression pro le and role of circRNAs in OS are not well understood.…”