Yang Chun, Deng Shaoping
School of Medicine, University of Electronic Science and Technology of China; Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
Arch Med Sci. 2019 Aug 20;18(6):1558-1571. doi: 10.5114/aoms.2019.87274. eCollection 2022.
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.
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.
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.
The regulatory network of hsa_circ_0017728/miR-149/IL-6/STAT3 cascade signaling might provide a better understanding of gastric carcinogenesis and progression.
环状RNA(circRNAs)已被确定为竞争性内源性RNA(ceRNAs),可介导参与包括胃癌(GC)在内的多种癌症进展的基因表达。然而,circRNAs调节GC细胞增殖和凋亡的潜在分子机制尚未完全阐明。在我们的研究中,对hsa_circ_0017728作为一种潜在的致癌竞争性内源性RNA(ceRNA)在胃癌发生发展过程中进行了研究。
采用高通量测序确定GC组织和相应癌旁组织中差异表达的circRNAs。进行CCK-8检测和膜联蛋白V-异硫氰酸荧光素/碘化丙啶(Annexin V-FITC/PI)染色以检测GC细胞的活力和凋亡情况。此外,分别使用RT-qPCR和蛋白质免疫印迹法检测GC组织和细胞系中的基因表达和蛋白质水平。
我们的结果表明,hsa_circ_0017728在GC组织和细胞系中的表达水平上调,且与总体生存率低、病理分化差、TNM分期高和淋巴结转移密切相关。敲低hsa_circ_0017728能够抑制GC细胞的增殖和迁移,并提高细胞凋亡率。我们还发现,hsa_circ_0017728可能作为ceRNA海绵吸附miR-149,并间接调节GC细胞增殖和凋亡中的IL-6/STAT3信号通路。
hsa_circ_0017728/miR-149/IL-6/STAT3级联信号的调控网络可能有助于更好地理解胃癌的发生和进展。