Interactions Between lncRNA TUG1 and miR-9-5p Modulate the Resistance of Breast Cancer Cells to Doxorubicin by Regulating eIF5A2.
Interactions Between lncRNA TUG1 and miR-9-5p Modulate the Resistance of Breast Cancer Cells to Doxorubicin by Regulating eIF5A2.
复制标题
lncRNA TUG1和miR-9-5p之间的相互作用通过调节eIF5A2调节乳腺癌细胞对阿霉素的耐药性
DOI：
10.2147/ott.s255113
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发表时间：
2020
影响因子：
4
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Wang S;Cheng M;Zheng X;Zheng L;Liu H;Lu J;Liu Y;Chen W
目的乳腺癌（BC）是癌症相关死亡的主要原因之一。BC的耐药性仍然是一个主要的未解决的临床障碍。TUG 1（牛磺酸上调基因1），一种长链非编码RNA（lncRNA）和microRNA（miRNA）与治疗耐药性有关。然而，TUG 1和调节BC中多柔比星（Dox）抗性的miRNA之间的相互作用仍然难以捉摸。材料与方法采用实时荧光定量PCR检测TUG 1和miR-9的表达。Western blot检测EIF 5A 2（真核翻译起始因子5A-2）的表达。siRNA或miRNA抑制剂的转染用于沉默lncRNA TUG 1、eIF 5A 2或miR-9。分别通过CCK-8（细胞计数试剂盒-8）、流式细胞术和EdU（5-乙炔基-2 β-脱氧尿苷）试验测定细胞活力、增殖和凋亡。通过荧光素酶测定确定TUG 1和miR-9之间的调节关系。结果LncRNA TUG 1在BC组织中高表达，与BC细胞对Dox的耐药性呈正相关。TUG 1的siRNA敲低逆转了MCF-7/ADR细胞中的Dox抗性。在机制上，TUG 1充当miR-9的“海绵”并下调miR-9。用miR-9抑制剂处理阻断了TUG 1 siRNA的作用，并且TUG 1的敲低抑制了miR-9的作用。此外，TUG 1抑制Dox诱导的细胞凋亡涉及miR-9靶向eIF 5A 2。结论TUG 1通过与miR-9相互作用调节eIF 5A 2的表达，从而调节BC细胞对Dox的敏感性。这些结果表明，lncRNA TUG 1可能是一个新的治疗乳腺癌的目标。
Purpose Breast cancer (BC) is one of the leading causes of cancer-related deaths. Chemoresistance of BC remains a major unmet clinical obstacle. TUG1 (taurine-upregulated gene 1), a long noncoding RNA (lncRNA), and microRNAs (miRNA) are implicated in therapeutic resistance. However, the interactions between TUG1 and miRNAs that regulate doxorubicin (Dox) resistance in BC remain elusive. Materials and Methods Expression of TUG1 and miR-9 was measured by real-time PCR. EIF5A2 (eukaryotic translation initiation factor 5A-2) was detected by Western blot. Transfection of siRNAs or miRNA inhibitors was applied to silence lncRNA TUG1, eIF5A2 or miR-9. Cell viability, proliferation, and apoptosis were determined by CCK-8 (cell counting kit-8), flow cytometry, and EdU (5-ethynyl-2ʹ-deoxyuridine) assays, respectively. The regulatory relationship between TUG1 and miR-9 was determined by a luciferase assay. Results LncRNA TUG1 was highly expressed in BC tissues and positively associated with Dox resistance in BC cell lines. SiRNA knockdown of TUG1 reversed Dox resistance in MCF-7/ADR cells. Mechanistically, TUG1 acted as a “sponge” for miR-9 and downregulated miR-9. Treatment with a miR-9 inhibitor blocked the effect of TUG1 siRNA, and knockdown of TUG1 inhibited the effects of miR-9. Furthermore, TUG1 inhibition of apoptosis induced by Dox involved miR-9 targeting of eIF5A2. Conclusion TUG1 modulates the susceptibility of BC cells to Dox by regulating the expression of eIF5A2 via interacting with miR-9. These results indicate that the lncRNA TUG1 may be a novel therapeutic target in breast cancer.