Xu Jiajia, Wang Xueqing, Wang Weijie, Zhang Lihua, Huang Peilin
Department of Clinical Pathology, Zhongda Hospital, Southeast University, Nanjing, China.
Department of Obstet & Gynaecol, Subei Peoples Hospital, Yangzhou, China.
J Gastrointest Oncol. 2021 Aug;12(4):1428-1443. doi: 10.21037/jgo-21-422.
The role of circular RNA (circRNA) in gastric cancer (GC) is attracting increasing attention. CircNOP10 (hsa_circ-0034351) has been reported to be upregulated in human GC tissue. However, the biological role and mechanism of circNOP10 in GC remain unknown.
Circular RNA expression profile of GC was detected based on microarray, and circNOP10 was identified for the subsequent investigation. Clinical samples of GC tissue and patient blood were obtained from the Zhongda Hospital, Southeast University. The different degraded GC cell lines were presented in our laboratory. The function and mechanism of circNOP10 in GC were investigated using Western blot, qRT-PCR, flow cytometry, in situ hybridization and pull down experiment.
The results indicated that increased circNOP10 in GC tissue was involved in tumor stage and prognosis. In addition, circNOP10 sponged microRNA-24 (miR-204)-mediated biological processes through sirtuin 1 (SIRT1), which further confirmed that the circNOP10/miR-204/SIRT1 pathway promoted proliferation and migration as well as epithelial-mesenchymal transition (EMT) through the NF-κβ pathway in GC cell lines.
Candidate oncogene circNOP10 mediated GC cell proliferation, arrest cell cycle in G/M phase, induced cell apoptosis, enhanced tumor metastasis, as well as EMT by activating the miR-204/SIRT1 pathway, suggesting that it may serve as a potential biomarker in GC therapy.
环状RNA（circRNA）在胃癌（GC）中的作用正受到越来越多的关注。据报道，circNOP10（hsa_circ-0034351）在人GC组织中上调。然而，circNOP10在GC中的生物学作用和机制仍不清楚。
基于微阵列检测GC的环状RNA表达谱，并鉴定circNOP10用于后续研究。GC组织和患者血液的临床样本取自东南大学附属中大医院。本实验室提供了不同降解程度的GC细胞系。采用蛋白质免疫印迹法、qRT-PCR、流式细胞术、原位杂交和下拉实验研究circNOP10在GC中的功能和机制。
结果表明，GC组织中circNOP10的增加与肿瘤分期和预后有关。此外，circNOP10通过沉默调节蛋白1（SIRT1）介导微小RNA-24（miR-204）相关的生物学过程，进一步证实circNOP10/miR-204/SIRT1通路通过NF-κβ通路促进GC细胞系的增殖、迁移以及上皮-间质转化（EMT）。
候选癌基因circNOP10通过激活miR-204/SIRT1通路介导GC细胞增殖，使细胞周期停滞在G/M期，诱导细胞凋亡，增强肿瘤转移以及EMT，提示其可能作为GC治疗中的潜在生物标志物。
