Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.
Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.
Bioengineered. 2021 Dec;12(1):8202-8216. doi: 10.1080/21655979.2021.1979915.
Gastric cancer (GC) is a serious digestive tract disease that threatens human life worldwide, and the prognosis of gastric cancer accompanied by distant lymph node or the distant metastasis organs is worse. The purpose of this study was to investigate the role of circular RNA COL6A3_030 (circBase ID: hsa_circ_0006401; circRNADb ID: hsa_circ_28198; circBank ID: hsa_circCOL6A3_030) in GC metastasis. qRT-PCR analysis using back-splicing primers and Sanger sequencing of PCR products were performed to identify circCOL6A3_030 in GC tissues and cell lines; RNA-FISH assay was performed to validate the subcellular localization of circCOL6A3_030. Transwell and wound-healing assays were carried out to evaluate the migration ability of GC cells. Western blot was conducted to detect the polypeptide encoded by circCOL6A3_030 in cells. circCOL6A3_030 was down-regulated in GC tissues and cell lines, while circCOL6A3_030 was up-regulated in GC with distant lymph node metastasis. The migration of circCOL6A3_030 silenced GC cells was significantly inhibited in both SGC-7901 and BGC-823 cell lines. Importantly, in vivo assay, silencing circCOL6A3_030 could reduce liver metastases from gastric cancer cells. Meanwhile, further studies suggested that circCOL6A3_030 encoded a small peptide that had a function as a tumor-promoting metastasis factor and immunohistochemistry confirmed the presence of this polypeptide. To sum up, our study showed that circCOL6A3_030 promoted GC cell migration by encoding a small peptide called circCOL6A3_030_198aa. Therefore, our results highlight the potential role of circCOL6A3_030 for clinical diagnosis and treatment of GC with distant lymph node metastasis.
胃癌(GC)是一种严重的消化道疾病,在全球范围内威胁着人类的生命,而伴有远处淋巴结或远处转移器官的胃癌预后更差。本研究旨在探讨环状 RNA COL6A3_030(环状 RNA 数据库 ID:hsa_circ_0006401;环状 RNA 数据库 ID:hsa_circ_28198;环状 RNA 数据库 ID:hsa_circCOL6A3_030)在 GC 转移中的作用。使用反向拼接引物进行 qRT-PCR 分析,并对 PCR 产物进行 Sanger 测序,以鉴定 GC 组织和细胞系中的 circCOL6A3_030;采用 RNA-FISH 实验验证 circCOL6A3_030 的亚细胞定位。通过 Transwell 和划痕愈合实验评估 GC 细胞的迁移能力。通过 Western blot 检测细胞中由 circCOL6A3_030 编码的多肽。circCOL6A3_030 在 GC 组织和细胞系中下调,而在伴有远处淋巴结转移的 GC 中上调。沉默 circCOL6A3_030 的 GC 细胞在 SGC-7901 和 BGC-823 细胞系中的迁移均显著受到抑制。重要的是,体内实验表明,沉默 circCOL6A3_030 可减少胃癌细胞的肝转移。同时,进一步的研究表明,circCOL6A3_030 编码一个具有促进肿瘤转移功能的小肽,免疫组织化学证实了该多肽的存在。总之,我们的研究表明,circCOL6A3_030 通过编码一个名为 circCOL6A3_030_198aa 的小肽促进 GC 细胞迁移。因此,我们的研究结果强调了 circCOL6A3_030 在诊断和治疗伴有远处淋巴结转移的 GC 方面的潜在作用。