Department of Thoracic Surgery, People's Hospital of Rizhao, China.
Life Sci. 2020 Oct 15;259:118157. doi: 10.1016/j.lfs.2020.118157. Epub 2020 Jul 28.
Previous studies have demonstrated that circular RNAs play significant roles in several tumors, including lung adenocarcinoma; however, specific biological functions and molecular mechanisms underlying this process remain unclear.
Here, we conducted real-time quantitative PCR (qRT-PCR) to measure hsa_circ_0001588 expression levels in 60 paired lung adenocarcinoma tissues and cell lines. Furthermore, the association between hsa_circ_0001588 and clinical features of lung adenocarcinoma was analyzed. Functional experiments were conducted to assess the influence of hsa_circ_0001588 on proliferation, migration, and invasion in lung adenocarcinoma cells. We detected possible downstream targets of hsa_circ_0001588 using bioinformatics analysis. Luciferase reporter assays, qRT-PCR, and western blotting assays were performed to verify the molecular mechanism underlying hsa_circ_0001588 functions.
We found that hsa_circ_0001588 was prominently upregulated in lung adenocarcinoma tissues and cell lines; elevated expression of hsa_circ_0001588 was positively correlated with poor clinicopathological features of lung adenocarcinoma. Functional experiments revealed that hsa_circ_0001588 acts as an oncogene to promote the proliferation, migration, and invasion of lung adenocarcinoma in vitro. Mechanistically, hsa_circ_0001588 promoted the proliferation, migration, and metastasis of lung adenocarcinoma by binding to miR-524-3p to promote nucleus accumbens-associated protein 1(NACC1) expression.
Together, our results revealed that hsa_circ_0001588 upregulated the expression of NACC1 by combining with miR-524-3p to promote the proliferation, migration, and invasion of lung adenocarcinoma cells, suggesting that hsa_circ_0001588 may be an underlying therapeutic target for lung adenocarcinoma.
先前的研究表明,环状 RNA 在包括肺腺癌在内的多种肿瘤中发挥着重要作用;然而,这一过程背后的具体生物学功能和分子机制仍不清楚。
在这里,我们通过实时定量 PCR(qRT-PCR)测量了 60 对肺腺癌组织和细胞系中 hsa_circ_0001588 的表达水平。此外,还分析了 hsa_circ_0001588 与肺腺癌临床特征之间的关联。进行功能实验以评估 hsa_circ_0001588 对肺腺癌细胞增殖、迁移和侵袭的影响。我们通过生物信息学分析检测 hsa_circ_0001588 的可能下游靶标。进行荧光素酶报告基因检测、qRT-PCR 和 Western blot 检测以验证 hsa_circ_0001588 功能的分子机制。
我们发现 hsa_circ_0001588 在肺腺癌组织和细胞系中显著上调;hsa_circ_0001588 的高表达与肺腺癌不良的临床病理特征呈正相关。功能实验表明,hsa_circ_0001588 作为一种癌基因,在体外促进肺腺癌细胞的增殖、迁移和侵袭。机制上,hsa_circ_0001588 通过与 miR-524-3p 结合促进核仁相关蛋白 1(NACC1)的表达,从而促进肺腺癌的增殖、迁移和转移。
总之,我们的研究结果表明,hsa_circ_0001588 通过与 miR-524-3p 结合上调 NACC1 的表达,促进肺腺癌细胞的增殖、迁移和侵袭,表明 hsa_circ_0001588 可能是肺腺癌的潜在治疗靶点。