Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, No. 100 Huaihai Avenue, Xinzhan District, Hefei City, 230000, Anhui Province, China.
Department of Hepatobiliary and Pancreatic Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, No. 98, Nantong West Road, Yangzhou City, 225001, Jiangsu Province, China.
Gastric Cancer. 2022 Jan;25(1):64-82. doi: 10.1007/s10120-021-01220-6. Epub 2021 Jul 22.
Gastric cancer (GC) is common in East Asia, yet its molecular and pathogenic mechanisms remain unclear. Circular RNAs (circRNAs) are differentially expressed in GC and may be promising biomarkers. Here, we investigated the role and regulatory mechanism of circTMC5 in GC.
CircTMC5 expression was detected in human GC and adjacent tissues using microarray assays and qRT-PCR, while the clinicopathological characteristics of patients with GC were used to assess its diagnostic and prognostic value. The circTMC5/miR-361-3p/RABL6 axis was examined in vitro and vivo, and the immune roles of RABL6 were evaluated using bioinformatics analyses and immunohistochemistry (IHC).
CircTMC5 was highly expressed in GC tissues, plasma, and cell lines, and was closely related to histological grade, pathological stage, and T classification in patients with GC. CircTMC5 expression was also an independent prognostic factor for GC and its combined detection with carcinoembryonic antigen may improve GC diagnosis. Low circTMC5 expression correlated with good prognosis, inhibited GC cell proliferation, and promoted apoptosis. Mechanistically, circTMC5 overexpression promoted GC cell proliferation, invasion, and metastasis but inhibited apoptosis by sponging miR-361-3p and up-regulating RABL6 in vitro and vivo, whereas miR-361-3p up-regulation had the opposite effects. RABL6 was highly expressed in GC and was involved in immune regulation and infiltration in GC.
CircTMC5 promotes GC and sponges miR-361-3p to up-regulate RABL6 expression, thus may have diagnostic and prognostic value in GC. RABL6 also displays therapeutic promise due to its role in the immune regulation of GC.
胃癌（GC）在东亚很常见，但它的分子和发病机制仍不清楚。环状 RNA（circRNAs）在 GC 中表达差异，可能是有前途的生物标志物。在这里，我们研究了 circTMC5 在 GC 中的作用和调节机制。
使用微阵列分析和 qRT-PCR 检测人 GC 及相邻组织中的 circTMC5 表达，同时评估 GC 患者的临床病理特征，以评估其诊断和预后价值。在体外和体内研究 circTMC5/miR-361-3p/RABL6 轴，使用生物信息学分析和免疫组织化学（IHC）评估 RABL6 的免疫作用。
circTMC5 在 GC 组织、血浆和细胞系中高表达，与 GC 患者的组织学分级、病理分期和 T 分类密切相关。circTMC5 表达也是 GC 的独立预后因素，与癌胚抗原联合检测可能提高 GC 的诊断。circTMC5 低表达与预后良好相关，抑制 GC 细胞增殖，促进凋亡。机制上，circTMC5 过表达通过在体外和体内吸附 miR-361-3p 并上调 RABL6 促进 GC 细胞增殖、侵袭和转移，但抑制凋亡，而 miR-361-3p 上调则有相反的作用。RABL6 在 GC 中高表达，并参与 GC 的免疫调节和浸润。
circTMC5 促进 GC 并吸附 miR-361-3p 上调 RABL6 表达，因此在 GC 中具有诊断和预后价值。由于 RABL6 在 GC 的免疫调节中的作用，它也具有治疗潜力。
