Background Circular RNA (circRNA) is increasingly attracting attention in gastric cancer (GC). Hsa_circ_0032821 (circ_0032821) has been declared to be upregulated in human GC tissues. However, the biological role of circ_0032821 remains undisclosed in GC cells. Methods Expression of circ_0032821 was measured by real-time quantitative PCR. Cell proliferation, autophagy, Epithelial-mesenchymal transition (EMT), migration, and invasion were evaluated by Cell counting kit-8 assay, western blotting or transwell assays. Expression of proliferating cell nuclear antigen (PCNA), Matrix metalloproteinase 2 (MMP2), MMP9, Light chain 3 (LC3), p62, total and phosphorylated Extracellular signal-regulated kinase 1/2 (ERK1/2) and Mitogen-activated protein kinase's kinase 1 (MEK1) was evaluated by western blotting. Xenograft tumor model was established to measure tumor growth in vivo. Results Circ_0032821 was significantly upregulated in human GC tumors and cells. Moreover, circ_0032821 might be a biomarker for the advanced Tumor node metastasis (TNM) stage, lymphoid node metastasis and poor prognosis in gastric cancer. Knockdown of circ_0032821 by transfection induced decrease of cell proliferation, EMT, migration and invasion, but increase of autophagy of AGS and HGC-27 cells in vitro, as well as induced tumor growth inhibition in vivo. Besides, overexpression of circ_0032821 by transfection functioned the opposite effects in human GC cells. Mechanically, the MEK1/ERK1/2 signaling pathway was activated when circ_0032821 upregulation, whereas inhibited when circ_0032821 silencing. Conclusion Circ_0032821 expression induced cell proliferation, EMT, migration, invasion, and autophagy inhibition in human GC cells in vitro and in vivo through activating MEK1/ERK1/2 signaling pathway, suggesting circ_0032821 as an oncogenic role in GC.

中文翻译：

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Circ_0032821 通过激活 MEK1/ERK1/2 信号通路在体外和体内作为人胃癌细胞增殖、转移和自噬的癌基因。

背景 环状RNA（circRNA）在胃癌（GC）中越来越受到关注。Hsa_circ_0032821 (circ_0032821) 已被宣布在人类 GC 组织中上调。然而，circ_0032821 在 GC 细胞中的生物学作用仍未公开。方法实时定量PCR检测circ_0032821的表达。细胞增殖、自噬、上皮间质转化 (EMT)、迁移和侵袭通过细胞计数试剂盒 8 测定、蛋白质印迹或 transwell 测定进行评估。增殖细胞核抗原 (PCNA)、基质金属蛋白酶 2 (MMP2)、MMP9、轻链 3 (LC3)、p62、总和磷酸化的细胞外信号调节激酶 1/2 (ERK1/2) 和丝裂原活化蛋白激酶的表达通过蛋白质印迹评估激酶1（MEK1）。建立异种移植肿瘤模型以测量体内肿瘤生长。结果 Circ_0032821 在人 GC 肿瘤和细胞中显着上调。此外，circ_0032821可能是胃癌晚期肿瘤淋巴结转移（TNM）分期、淋巴结转移和预后不良的生物标志物。通过转染敲低 circ_0032821 可诱导细胞增殖、EMT、迁移和侵袭减少，但在体外增加 AGS 和 HGC-27 细胞的自噬，并在体内诱导肿瘤生长抑制。此外，通过转染过表达 circ_0032821 在人类 GC 细胞中起到相反的作用。机械地，当 circ_0032821 上调时，MEK1/ERK1/2 信号通路被激活，而当 circ_0032821 沉默时，MEK1/ERK1/2 信号通路被抑制。结论 Circ_0032821 表达诱导细胞增殖、EMT、