Background

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.

Methods

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).

Results

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.

Conclusions

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.

中文翻译：

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CircTMC5通过靶向miR-361-3p/RABL6促进胃癌进展和转移

背景

胃癌（GC）在东亚很常见，但其分子和致病机制仍不清楚。环状 RNA (circRNA) 在 GC 中差异表达，可能是有前途的生物标志物。在这里，我们研究了 circTMC5 在 GC 中的作用和调控机制。

方法

使用微阵列分析和 qRT-PCR 在人类 GC 和邻近组织中检测到 CircTMC5 表达，而 GC 患者的临床病理学特征用于评估其诊断和预后价值。在体外和体内检测了 circTMC5/miR-361-3p/RABL6 轴，并使用生物信息学分析和免疫组织化学 (IHC) 评估了 RABL6 的免疫作用。

结果

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、T分期密切相关。CircTMC5 表达也是 GC 的独立预后因素，其与癌胚抗原联合检测可提高 GC 诊断水平。circTMC5 低表达与良好预后相关，抑制 GC 细胞增殖，促进细胞凋亡。从机制上讲，circTMC5 过表达促进 GC 细胞增殖、侵袭和转移，但通过在体外和体内作用于 miR-361-3p 和上调 RABL6 来抑制细胞凋亡，而 miR-361-3p 上调具有相反的作用。RABL6在GC中高表达，参与GC中的免疫调节和浸润。

结论

CircTMC5 促进 GC 并吸收 miR-361-3p 上调 RABL6 表达，因此可能对 GC 具有诊断和预后价值。RABL6 还因其在 GC 免疫调节中的作用而显示出治疗前景。