Exosome-transferred hsa_circ_0014235 promotes DDP chemoresistance and deteriorates the development of non-small cell lung cancer by mediating the miR-520a-5p/CDK4 pathway.
Exosome-transferred hsa_circ_0014235 promotes DDP chemoresistance and deteriorates the development of non-small cell lung cancer by mediating the miR-520a-5p/CDK4 pathway.
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外泌体转移的hsa_circ_0014235通过介导miR-520 a-5 p/CDK 4通路促进DDP化疗耐药性并恶化非小细胞肺癌的发展
DOI：
10.1186/s12935-020-01642-9
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发表时间：
2020-11-17
影响因子：
5.8
通讯作者：
Ji X
中科院分区：
文献类型：
--
作者：
Xu X;Tao R;Sun L;Ji X
环状RNA（circRNA）在包括非小细胞肺癌（NSCLC）在内的人类癌症的发生和发展中起着至关重要的作用。然而，这些circRNA中的大多数，如hsa_circ_0014235，在功能和机制上还没有完全确定。使用透射电子显微镜（TEM）鉴定从血清样品分离的外泌体。实时定量聚合酶链反应（qPCR）检测hsa_circ_0014235、miR-520 a-5 p和细胞周期蛋白依赖性激酶4（CDK 4）的表达。对于功能测定，分别使用细胞计数试剂盒-8（CCK-8）测定、集落形成测定、伤口愈合测定、transwell测定和流式细胞术测定来测定细胞增殖、集落形成能力、迁移、侵袭、细胞凋亡和细胞周期进程。Western blot检测CDK 4等标志蛋白的表达。通过双荧光素酶报告基因测定或RNA免疫沉淀（RIP）测定验证miR-520 a-5 p与hsa_circ_0014235或细胞周期蛋白依赖性激酶4（CDK 4）之间的预测靶向关系。hsa_circ_0014235在NSCLC血清来源的外泌体、肿瘤组织和细胞中的表达显著升高。NSCLC血清来源的外泌体在体外促进NSCLC细胞对顺铂（DDP）的耐药性、细胞增殖、迁移和侵袭，以及在体内促进肿瘤生长和DDP耐药性。Hsa_circ_0014235过表达增强DDP耐药性并促进细胞恶性行为。miR-520 a-5 p是hsa_circ_0014235的靶标，并且挽救实验显示miR-520 a-5 p恢复逆转了hsa_circ_0014235过表达的作用。此外，CDK 4是miR-520 a-5 p的靶点，挽救实验表明CDK 4敲低逆转了miR-520 a-5 p抑制对NSCLC进展的侵袭性作用。外泌体介导的hsa_circ_0014235通过介导miR-520 a-5 p/CDK 4调控轴促进NSCLC恶性发展。
Circular RNAs (circRNAs) play crucial roles in the development and progression of human cancers, including non-small cell lung cancer (NSCLC). However, most of these circRNAs, such as hsa_circ_0014235, are not fully identified in functions and mechanisms. The isolated exosomes from serum specimens were identified using transmission electron microscopy (TEM). The expression of hsa_circ_0014235, miR-520a-5p and cyclin-dependent kinase 4 (CDK4) was detected by real-time quantitative polymerase chain reaction (qPCR). For functional assays, cell proliferation, colony formation ability, migration, invasion, cell apoptosis and cell cycle progression were determined using cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay, transwell assay and flow cytometry assay, respectively. The expression of CDK4 and other indicated marker proteins was detected by western blot. The predicted target relationship between miR-520a-5p and hsa_circ_0014235 or cyclin-dependent kinase 4 (CDK4) was verified by dual-luciferase reporter assay or RNA immunoprecipitation (RIP) assay. The expression of hsa_circ_0014235 was notably elevated in NSCLC serum-derived exosomes, tumor tissues and cells. NSCLC serum-derived exosomes promoted NSCLC cell resistance to cisplatin (DDP), cell proliferation, migration and invasion in vitro, as well as tumor growth and DDP resistance in vivo. Hsa_circ_0014235 overexpression enhanced DDP resistance and facilitated cell malignant behaviors. MiR-520a-5p was a target of hsa_circ_0014235, and rescue experiments showed that miR-520a-5p restoration reversed the effects of hsa_circ_0014235 overexpression. Moreover, CDK4 was a target of miR-520a-5p, and rescue experiments showed that CDK4 knockdown reversed the aggressive effects of miR-520a-5p inhibition on NSCLC progression. Exosome-transmitted hsa_circ_0014235 promoted NSCLC malignant development by mediating the miR-520a-5p/CDK4 regulatory axis.
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影响因子：
2.3
作者：
Fujimoto J;Wistuba II
通讯作者：
Wistuba II
DOI：
10.1158/1078-0432.ccr-14-2748
发表时间：
2015-05-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Politi K;Herbst RS
通讯作者：
Herbst RS
circRNA生物合成的调控
影响因子：
4.1
作者：
Chen, Ling-Ling;Yang, Li
通讯作者：
Yang, Li
circ-SEC31A 高表达通过调节 miR-520a-5p/GOT-2 轴预测非小细胞肺癌的不良预后
影响因子：
5.2
作者：
Jin, Mingming;Shi, Chunzi;Huang, Gang
通讯作者：
Huang, Gang
影响因子：
37.3
作者：
Tan S;Sun D;Pu W;Gou Q;Guo C;Gong Y;Li J;Wei YQ;Liu L;Zhao Y;Peng Y
通讯作者：
Peng Y