Circular RNA circCRIM1 inhibits invasion and metastasis in lung adenocarcinoma through the microRNA (miR)-182/miR-93-leukemia inhibitory factor receptor pathway
Circular RNA circCRIM1 inhibits invasion and metastasis in lung adenocarcinoma through the microRNA (miR)-182/miR-93-leukemia inhibitory factor receptor pathway
复制标题
环状RNA circCRIM1通过microRNA (miR)-182/miR-93-白血病抑制因子受体通路抑制肺腺癌侵袭和转移
DOI：
10.1111/cas.14131
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发表时间：
2019-08-14
期刊：
影响因子：
5.7
通讯作者：
Dong, Gaochao
中科院分区：
文献类型：
--
作者：
Wang, Lin;Liang, Yingkuan;Dong, Gaochao
近年来，人们发现环状RNA（circular RNA，circRNA）在肿瘤的发生发展中起着重要作用。转移是肺腺癌（LUAC）死亡的主要原因。然而，circRNA对LUAC转移的贡献在很大程度上仍然未知。根据circBase数据和我们的生物库组织，我们鉴定出circCRIM 1（一种源自CRIM 1基因外显子2、3和4的circRNA，hsa_circ_0002346）与匹配的正常对照样本相比，在LUAC样本中的表达显着降低。体内和体外实验均显示circCRIM 1抑制LUAC的侵袭和转移。通过体外circRNA沉淀、荧光素酶报告基因检测和生物素偶联的microRNA捕获来研究circCRIM 1和microRNA（miR）-93/miR-182的Ago 2依赖性相互作用。从机制上讲，我们发现circCRIM 1可以通过吸收miR-93和miR-182来促进白血病抑制因子受体（一种众所周知的肿瘤抑制因子）的表达。在临床和病理分析中，circCRIM 1在LUAC中的下调与淋巴结转移和TNM分期显著相关，是影响LUAC患者总生存率的独立危险因素。我们的研究表明，circCRIM 1抑制肺腺癌细胞的侵袭和转移，这使其成为潜在的治疗靶点。
In recent years, circular RNAs (circRNAs) have been revealed to have important roles in carcinogenesis. Metastasis is the leading cause of lung adenocarcinoma (LUAC) death. However, the contributions of circRNA to the metastasis of LUAC remain largely unknown. Based on circBase data and our biobank tissues, we identified circCRIM1 (a circRNA derived from exons 2, 3 and 4 of the CRIM1 gene, hsa_circ_0002346) as having a significantly decreased expression in LUAC samples compared with matched normal control samples. Both in vivo and in vitro experiments revealed that circCRIM1 suppresses the invasion and metastasis of LUAC. In vitro precipitation of circRNAs, luciferase reporter assay, and biotin-coupled microRNA capture were carried out to investigate the Ago2-dependent interaction of circCRIM1 and microRNA (miR)-93/miR-182. Mechanistically, we found that circCRIM1 could promote the expression of leukemia inhibitory factor receptor, a well-known tumor suppressor, by sponging miR-93 and miR-182. In the clinical and pathological analyses, the downregulation of circCRIM1 in LUAC was significantly correlated with lymphatic metastasis and TNM stage, which served as an independent risk factor for the overall survival of patients with LUAC. Our study showed that circCRIM1 inhibits the invasion and metastasis of lung adenocarcinoma cancer cells, which makes it a potential therapeutic target.