miR-223 increases gallbladder cancer cell sensitivity to docetaxel by downregulating STMN1.
miR-223 increases gallbladder cancer cell sensitivity to docetaxel by downregulating STMN1.
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DOI：
10.18632/oncotarget.11634
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发表时间：
2016-09-20
期刊：
影响因子：
--
通讯作者：
Liu Y
中科院分区：
文献类型：
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作者：
Lu W;Hu Y;Ma Q;Zhou L;Jiang L;Li Z;Zhao S;Xu Y;Shi W;Li S;Liu Y
MicroRNA (miR) 参与癌症的发生，某些调节性 miR 可以为胆囊癌 (GBC) 等难治性恶性肿瘤提供有前景的治疗方法。人们发现 miR-223 在增强化疗效果方面发挥着关键作用，因此引起了人们对 miR-223 在 GBC 中作用的兴趣。 miR-223在GBC组织和细胞系中减少，异位miR-223表达在GBC细胞中表现出多种抗肿瘤作用，包括体外增殖、迁移和侵袭减少。然而，用 miR-223 抑制剂治疗可增加细胞活力。我们确定 GBC 中 STMN1 与 miR-223 呈负相关并受 miR-223 调节。 miR-223在体外和体内增加GBC对多西紫杉醇的敏感性，并且通过恢复STMN1表达来抑制诱导的对多西紫杉醇的敏感性。我们使用 qRT-PCR 检查了 GBC 组织和 GBC 细胞系中的 miR-223 表达。使用细胞计数试剂盒-8 (CCK8)、流式细胞术以及伤口愈合和侵袭测定来测定 GBC 细胞中调节的 miR-223 表达的影响。在 miR-223/STMN1 调节的 GBC 细胞和异种移植肿瘤模型中评估了对多西紫杉醇的敏感性。通过Western blotting检测相关基因的蛋白表达。这些发现表明，miR-223 可能作为一种肿瘤抑制剂，通过下调 GBC 中的 STMN1 来增强对多西紫杉醇的敏感性，凸显了其有前景的治疗价值。
MicroRNAs (miRs) are involved in cancer carcinogenesis, and certain regulatory miRs could provide promising therapeutic methods for refractory malignancies, such as gallbladder cancer (GBC). miR-223 was found to play a pivotal role in enhancing chemotherapeutic effects, therefore evoking interest in the role of miR-223 in GBC. miR-223 was decreased in GBC tissues and cell lines, and ectopic miR- 223 expression exhibited multiple anti-tumorigenic effects in GBC cells, including decreased proliferation, migration and invasion in vitro. However, treatment with a miR-223 inhibitor increased cell viability. We determined that STMN1 was negatively correlated with and regulated by miR-223 in GBC. miR-223 increased GBC sensitivity to docetaxel in vitro and in vivo, and the induced sensitivity to docetaxel was suppressed by the restoration of STMN1 expression. We examined miR-223 expression in GBC tissue and GBC cell lines using qRT-PCR. The effects of modulated miR-223 expression in GBC cells were assayed using Cell Counting Kit-8 (CCK8), flow cytometry, and wound-healing and invasion assays. Susceptibility to docetaxel was evaluated in miR-223/STMN1-modulated GBC cells and xenograft tumor models. The protein expression of relevant genes was examined by Western blotting. These findings indicated that miR-223 might serve as an onco-suppressor that enhances susceptibility to docetaxel by downregulating STMN1 in GBC, highlighting its promising therapeutic value.