Abstract
BackgroundCircular 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.MethodsExpression 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.ResultsCirc_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.ConclusionCirc_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.
Highlights
Circular RNA is increasingly attracting attention in gastric cancer (GC)
Even though over 90% patients with early GC survive for 5 years, the advanced GC patients harbor a poor prognosis statistically [2]
Afterwards, these 20 circRNAs were further identified in a cohort of GC patients (n = 60) using RT-qPCR
Summary
Circular RNA (circRNA) is increasingly attracting attention in gastric cancer (GC). Gastric cancer (GC) is the third tumor mortality worldwide [1]. The prognosis of GC patients is inversely proportional to the cancer stage. Even though over 90% patients with early GC survive for 5 years, the advanced GC patients harbor a poor prognosis statistically [2]. The incidence of GC remains high in China, whereas less than 20% GC patients are diagnosed at early stages [3, 4]. Tumor invasiveness and distant metastasis always happen after operation, limiting its efficiency [6]. It is essential to explore the deep mechanisms responsible for GC metastasis, and to investigate new targets for the detection of early GC
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