Qin Jing, Zhen Shuman, Wang Jiali, Lv Wei, Zhao Yan, Duan Yuqing, Liu Tianxu, Feng Lei, Wang Guiying, Liu Lihua
Department of Tumor Immunotherapy, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Department of General Surgery, Third Hospital of Shijiazhuang, Shijiazhuang, China.
J Gastrointest Oncol. 2023 Jun 30;14(3):1259-1278. doi: 10.21037/jgo-23-240. Epub 2023 May 15.
Mounting evidences indicate that circular RNAs (circRNAs) are a novel class of non-coding RNAs and play vital roles in the tumorigenesis and aggressiveness including gastric cancer (GC). Nevertheless, the precise functions and underlying mechanisms of circRNAs in GC remain largely unknown.
The Gene Expression Omnibus (GEO) data set GSE163416 was analyzed to screen the key circRNAs in GC. was chosen for further study. GC tissues and matched adjacent normal gastric mucosal epithelial tissues were obtained from the Fourth Hospital of Hebei Medical University. The expressions of was detected using quantitative real-time polymerase chain reaction (qRT-PCR). was knocked down to identify its effects on GC cells. Bioinformatics algorithms were analyzed to predict the microRNA (miRNAs) potentially sponged by and its target genes. Fluorescence in situ hybridization (FISH) was conducted to determine the subcellular location of and the predicted miRNA. Then, qRT-PCR, luciferase reporter assay, radioimmunoprecipitation assay, Western blotting, and miRNA rescue experiments were used to confirm the -related regulatory axis in GC. Cell Counting Kit-8 (CCK-8), colony formation, wound healing, and Transwell experiments were performed to determine the effect of the hsa_-related regulatory axis on GC cells' malignant behaviors . The xenograft tumor mouse model was established to evaluate the effect of .
exhibited a high expression in GC tissues as compared to corresponding adjacent normal gastric mucosal epithelial tissues and its high expression was positively correlated with TNM stage, lymph node invasion and poor prognosis (P<0.05). Knockdown of suppressed the proliferation, colony formation, migration, and invasion in GC cells (all P<0.05). upregulated high mobility group box 1 () by sponging in GC cells (P<0.05). The - axis promoted malignant behaviors and epithelial-mesenchymal transition (EMT) in GC cells by activating the Wnt/β-catenin pathway (P<0.05). The existence of - axis was confirmed in GC specimens (P<0.05). Consequently, down-regulated inhibited the progression and EMT of GC cells (P<0.05).
For the first time, we demonstrated that axis exerted its tumor-promoting effects in GC, which suggested that could be potentially targeted for GC treatment.
越来越多的证据表明，环状RNA（circRNAs）是一类新型的非编码RNA，在包括胃癌（GC）在内的肿瘤发生和侵袭过程中发挥着至关重要的作用。然而，circRNAs在GC中的具体功能和潜在机制仍 largely未知。
分析基因表达综合数据库（GEO）数据集GSE163416以筛选GC中的关键circRNAs。选择 进行进一步研究。从河北医科大学第四医院获取GC组织和匹配的相邻正常胃黏膜上皮组织。使用定量实时聚合酶链反应（qRT-PCR）检测 的表达。敲低 以确定其对GC细胞的影响。分析生物信息学算法以预测可能被 吸附的微小RNA（miRNAs）及其靶基因。进行荧光原位杂交（FISH）以确定 的亚细胞定位和预测的miRNA。然后，使用qRT-PCR、荧光素酶报告基因检测、放射免疫沉淀检测、蛋白质免疫印迹和miRNA拯救实验来证实GC中与 相关的调控轴。进行细胞计数试剂盒-8（CCK-8）、集落形成、伤口愈合和Transwell实验以确定hsa_-相关调控轴对GC细胞恶性行为的影响 。建立异种移植肿瘤小鼠模型以评估 的作用。
与相应的相邻正常胃黏膜上皮组织相比， 在GC组织中表现出高表达，其高表达与TNM分期、淋巴结侵袭和不良预后呈正相关（P<0.05）。敲低 可抑制GC细胞的增殖、集落形成、迁移和侵袭（均P<0.05）。 在GC细胞中通过吸附 上调高迁移率族蛋白盒1（ ）（P<0.05）。 -轴通过激活Wnt/β-连环蛋白途径促进GC细胞的恶性行为和上皮-间质转化（EMT）（P<0.05）。在GC标本中证实了 -轴的存在（P<0.05）。因此，下调 可抑制GC细胞的进展和EMT （P<0.05）。
我们首次证明 轴在GC中发挥促肿瘤作用，这表明 可能是GC治疗的潜在靶点。
