Circular RNA hsa_circ_0001588 promotes the malignant progression of lung adenocarcinoma by modulating miR-524-3p/NACC1 signaling
Circular RNA hsa_circ_0001588 promotes the malignant progression of lung adenocarcinoma by modulating miR-524-3p/NACC1 signaling
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DOI：
10.1016/j.lfs.2020.118157
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发表时间：
2020-10-15
期刊：
影响因子：
6.1
通讯作者：
Sun, Zhaoyi
中科院分区：
文献类型：
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作者：
Sun, Zhaoyi
目的：以往的研究表明，环状RNA发挥重要作用，在一些肿瘤，包括肺腺癌，然而，具体的生物学功能和分子机制，这一过程的基础上仍然不清楚。材料和方法：在这里，我们进行了实时定量PCR（qRT-PCR），以测量hsa_circ_0001588在60对肺腺癌组织和细胞系的表达水平。进一步分析hsa_circ_0001588与肺腺癌临床特征的关系。通过功能实验研究hsa_circ_0001588对肺腺癌细胞增殖、迁移和侵袭的影响。我们利用生物信息学分析检测了hsa_circ_0001588可能的下游靶点。通过荧光素酶报告基因检测、qRT-PCR和蛋白质印迹分析验证了hsa_circ_0001588功能的分子机制。关键发现：hsa_circ_0001588在肺腺癌组织和细胞系中显著上调; hsa_circ_0001588的高表达与肺腺癌的不良临床病理特征呈正相关。功能实验显示hsa_circ_0001588作为癌基因在体外促进肺腺癌的增殖、迁移和侵袭。hsa_circ_0001588通过与miR 524 - 3 p结合促进核转录相关蛋白1（NACC 1）的表达，促进肺腺癌的增殖、迁移和转移。总之，我们的结果显示，hsa_circ_0001588通过与miR-524- 3 p结合来上调NACC 1的表达，从而促进细胞增殖、迁移，和肺腺癌细胞的侵袭，表明HSA_circ_0001588可能是肺腺癌的潜在治疗靶点。
Aims: 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.Materials and methods: 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 ade-nocarcinoma 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.Key findings: 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 miR524-3p to promote nucleus accumbens-associated protein 1(NACC1) expression.Significance: 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.