A novel circular RNA circFN1 enhances cisplatin resistance in gastric cancer via sponging miR-182-5p
A novel circular RNA circFN1 enhances cisplatin resistance in gastric cancer via sponging miR-182-5p
复制标题
新型环状RNA circFN1通过海绵miR-182-5p增强胃癌顺铂耐药性
DOI：
10.1002/jcb.29641
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发表时间：
2020-01-02
影响因子：
4
通讯作者：
Xu, Li
中科院分区：
文献类型：
--
作者：
Huang, Xiao-xu;Zhang, Qiang;Xu, Li
顺铂（CDDP）是胃癌（GC）化疗的常用药物。然而，经过几个以cddp为基础的治疗周期后，患者往往会产生化疗耐药，这限制了治疗的整体临床疗效。为了改善患者的治疗效果，需要澄清CDDP耐药的机制。环状rna （circRNAs）是参与癌症发病机制的非编码rna，尽管它们在GC中CDDP耐药机制中的作用尚不清楚。在本研究中，我们探讨了circRNAs在CDDP敏感和CDDP耐药的人GC细胞中调节CDDP抗性的潜在作用。通过RNA测序和定量逆转录聚合酶链反应，circFN1（源自FN1基因hsa_circ_0058147的第10,11和12外显子）在耐cddp的GC细胞和组织中表达较高。在CDDP治疗的GC患者中，CircFN1表达上调与侵袭性生物学行为显著相关。在体内和体外实验中，CircFN1促进CDDP暴露的GC细胞的活力并抑制凋亡。此外，circFN1通过“海绵”miR-182-5p抑制GC细胞凋亡。这些发现表明circFN1参与了GC的CDDP耐药性，并暗示circFN1是CDDP治疗的GC患者的治疗靶点。它为环状rna作为microRNA海绵的功能提供了新的证据，并突出了消除GC患者CDDP耐药的潜在治疗靶点。
Cisplatin (CDDP) is commonly used for gastric cancer (GC) chemotherapy. However, after several CDDP-based treatment cycles, patients always acquire chemotherapy resistance, which limits the overall clinical efficacy of the treatment. Clarification of the mechanisms responsible for CDDP resistance is required to improve therapeutic outcomes for patients. Circular RNAs (circRNAs) are noncoding RNAs involved in the pathogenesis of cancer, although their role in the mechanism underlying CDDP resistance in GC remains unknown. In the present study, we explored the underlying roles of circRNAs in the modulation of CDDP resistance in CDDP-sensitive and CDDP-resistant human GC cells. Using RNA sequencing and quantitative reverse transcription polymerase chain reaction, expression of circFN1 (originating from exons 10, 11, and 12 of the FN1 gene hsa_circ_0058147) was higher in CDDP-resistant GC cells and tissues. CircFN1 upregulation in GC patients treated by CDDP was significantly correlated with aggressive biological behavior. CircFN1 promoted viability and inhibited apoptosis of GC cells exposed to CDDP in vivo and in vitro. Furthermore, circFN1 suppressed GC cell apoptosis by "sponging" miR-182-5p. These findings demonstrate the involvement of circFN1 in CDDP resistance of GC and implicate circFN1 as a therapeutic target for GC patients treated with CDDP. It provides novel evidence of the function of circRNAs as microRNA sponges and highlight a potential therapeutic target for extinguishing CDDP resistance in patients with GC.