Lin Jie, Zhu Qiuping, Zeng Fanlin
Department of Intensive Medicine/Comprehensive Intensive Care Unit, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.
Department of General Surgery/Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.
Neoplasma. 2024 Dec;71(6):581-593. doi: 10.4149/neo_2024_240604N243.
Esophageal squamous cell carcinoma (ESCC) has high mortality. The role and regulatory mechanism of hsa_circ_0021727 (circ_0021727) in ESCC remain largely unknown. This study focused on the undiscovered impact of circ_0021727 on cell cycle progression, apoptosis, and angiogenesis of ESCC. We found that circ_0021727 levels were significantly upregulated in ESCC cells. TUNEL, flow cytometry, and tubule formation assay indicated that knockdown of circ_0021727 in ESCC induced cell arrest at the G0/G1 phase, promoted apoptosis, and inhibited angiogenesis, whereas overexpression of circ_0021727 produced the opposite effect. Gastrulation brain homeobox 2 (GBX2) GBX2 was a downstream target gene of circ_0021727, and overexpression of GBX2 reversed the effect of circ_0021727 knockdown in ESCC progression. The results of the RIP and RNA pull-down showed that circ_0021727 and GBX2 mRNA bound with eukaryotic translation initiation factor 4A3 (EIF4A3). Overexpression of circ_0021727 promoted GBX2 mRNA stability by binding with EIF4A3. In a tumor xenograft model, the knockdown of circ_0021727 inhibited tumor growth, which was reversed by further overexpression of GBX2. In conclusion, circ_0021727 increased GBX2 mRNA stability by recruiting EIF4A3, which promoted cell cycle progression and angiogenesis in ESCC.
食管鳞状细胞癌（ESCC）死亡率很高。hsa_circ_0021727（circ_0021727）在ESCC中的作用和调控机制在很大程度上仍不清楚。本研究聚焦于circ_0021727对ESCC细胞周期进程、细胞凋亡和血管生成的未被发现的影响。我们发现ESCC细胞中circ_0021727水平显著上调。TUNEL法检测、流式细胞术和小管形成试验表明，敲低ESCC中的circ_0021727可诱导细胞停滞于G0/G1期，促进细胞凋亡并抑制血管生成，而circ_0021727过表达则产生相反的效果。原肠胚脑同源盒2（GBX2）是circ_0021727的下游靶基因，GBX2过表达可逆转circ_0021727敲低对ESCC进展的影响。RNA免疫沉淀（RIP）和RNA下拉实验结果表明，circ_0021727和GBX2 mRNA与真核翻译起始因子4A3（EIF4A3）结合。circ_0021727过表达通过与EIF4A3结合促进GBX2 mRNA稳定性。在肿瘤异种移植模型中，敲低circ_0021727可抑制肿瘤生长，而进一步过表达GBX2可逆转这一作用。总之，circ_0021727通过招募EIF4A3增加GBX2 mRNA稳定性，从而促进ESCC细胞周期进程和血管生成。
