Hsa_circ_0017728 as an oncogene in gastric cancer by sponging miR-149 and modulating the IL-6/STAT3 pathway

Abstract

Introduction: Circular RNAs (circRNAs) have been identified as competing endogenous RNAs (ceRNAs) to mediate gene expression participating in the progression of multiple cancers, including gastric carcinoma (GC). However, the underlying molecular mechanisms by which circRNAs-modulated cell proliferation and apoptosis in GC had not been completely clarified. In our study, hsa_ circ_0017728 as a potential oncogene competing endogenous RNA (ceRNA) was investigated in the progression and development of gastric carcinogenesis. Material and methods: High-throughput sequencing was used to determine differentially expressed circRNAs in GC tissues and corresponding non-cancerous tissues. The CCK-8 assay and Annexin V-fluorescein isothiocyanate/ polyimide (Annexin V-FITC/PI) staining were performed to detect the cell viability and apoptosis in GC cells. In addition, gene expression and protein levels in GC tissues and cell lines were measured using RT-qPCR and western blotting, respectively. Results: Our results demonstrated that the hsa_circ_0017728 expression level was up-regulated in GC tissues and cell lines and closely associated with poor overall survival and pathological differentiation, higher TNM stage and lymph node metastasis. Knockdown of hsa_circ_0017728 had the ability to cause inhibition of cell proliferation and migration and elevate the cell apoptosis rate in GC cells. We also discovered that hsa_circ_0017728 might serve as a ceRNA to sponge miR-149 and indirectly regulated the IL-6/STAT3 signaling pathway in GC cell proliferation and apoptosis. Conclusions: The regulatory network of hsa_circ_0017728/miR-149/IL-6/ STAT3 cascade signaling might provide a better understanding of gastric carcinogenesis and progression.

The Biological Role of Sponge Circular RNAs in Gastric Cancer: Main Players or Coadjuvants?

“…They can also act as templates for protein translation and mediate immune responses [ 7 , 8 ]. Dysregulation in their role as miRNA-sponge has been reported in several types of gastrointestinal malignancies, including hepatocellular carcinoma [ 9 , 10 , 11 ], pancreatic [ 10 , 12 ], colorectal [ 10 , 11 , 13 ] and gastric cancer [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ,…”

“…A large number of studies have demonstrated the role of circRNAs as miRNA-sponges in GC [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. For example, it has been shown that alterations in circLARP4/miR-424/LATS1 [ ...…”