Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Molecular Cell Biology and Toxicology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
Cancer Sci. 2020 Aug;111(8):2824-2836. doi: 10.1111/cas.14511. Epub 2020 Jul 15.
In this study, we explored expression and functions of circular RNA LPAR3 (circLPAR3) in esophageal squamous cell carcinoma (ESCC). The differential expression of circular RNAs (circRNAs) in 10 ESCC and corresponding paracarcinoma tissues was analyzed through circRNA microarray, then the candidate circRNAs were detected and verified through quantitative RT-PCR, and a novel circRNA was screened, which was circLPAR3. Circular RNA LPAR3 showed apparently high expression in ESCC tissues and cells, which was closely correlated with the clinical stage and lymph node metastasis of ESCC patients. Circular RNA LPAR3 was mainly located in the cytoplasm of ESCC cells, which was more stable than the baseline gene. Circular RNA LPAR3 upregulated MET gene expression through sponge adsorption of microRNA (miR)-198, activated the RAS/MAPK and the PI3K/Akt pathways, and promoted ESCC cell migration, invasion, and metastasis in vivo and in vitro. However, it had no effect on ESCC cell proliferation. Circular RNA LPAR3 can regulate the miR-198-MET signal axis to promote the migration, invasion, and metastasis of esophageal cancer cells, which can thereby serve as a potential diagnostic and therapeutic target of esophageal cancer.
在这项研究中,我们探讨了环状 RNA LPAR3(circLPAR3)在食管鳞状细胞癌(ESCC)中的表达和功能。通过环状 RNA 微阵列分析了 10 例 ESCC 及其相应癌旁组织中环状 RNA(circRNAs)的差异表达,然后通过定量 RT-PCR 检测和验证候选 circRNAs,并筛选出一种新型 circRNA,即 circLPAR3。circLPAR3 在 ESCC 组织和细胞中表达明显升高,与 ESCC 患者的临床分期和淋巴结转移密切相关。circLPAR3 主要位于 ESCC 细胞的细胞质中,其稳定性高于基线基因。circLPAR3 通过海绵吸附 microRNA(miR)-198 上调 MET 基因表达,激活 RAS/MAPK 和 PI3K/Akt 通路,促进 ESCC 细胞在体内和体外的迁移、侵袭和转移。然而,它对 ESCC 细胞的增殖没有影响。circLPAR3 可以调节 miR-198-MET 信号轴,促进食管癌的迁移、侵袭和转移,因此可以作为食管癌潜在的诊断和治疗靶点。