长链非编码 RNA SNHG6 通过 EZH2/STAT 通路沉默使食管癌细胞对 5-FU 敏感。
Long noncoding RNA SNHG6 silencing sensitized esophageal cancer cells to 5-FU via EZH2/STAT pathway.
机构信息
Department of Clinical Pharmacy, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Translational Medical Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
出版信息
Sci Rep. 2023 Apr 1;13(1):5363. doi: 10.1038/s41598-023-32607-3.
Chemotherapy was the main treatment method for esophageal cancer (EC) patients. However, chemotherapy resistance due to multiple factors is a major barrier to EC treatment. For investigating how small nucleolar RNA host gene 6 (SNHG6) affected the 5-fluorouracil (5-FU) resistance in EC as well as its possible molecular mechanism. This work conducted cell viability assay, clone formation, scratch assays together with cell apoptosis for evaluating the roles of SNHG6 and enhancer of zeste homolog 2 (EZH2, the histone-lysine N-methyltransferase). Relevant molecular mechanism was identified by RT-qPCR analysis together with Western-blot (WB) assays. Our data showed that SNHG6 expression increased in EC cells. SNHG6 promotes colony formation and migration, whereas suppresses EC cell apoptosis. SNHG6 silencing markedly promoted 5-FU-mediated suppression on KYSE150 and KYSE450 cells. Additional mechanism studies showed that SNHG6 modulating STAT3 and H3K27me3 via promoting EZH2 level. Similar to the function of SNHG6, abnormal expression of EZH2 promotes the malignancy of EC and intensifies its resistance to 5-FU. In addition, overexpression of EZH2 abolished the role of SNHG6 silencing in 5-FU sensitivity in EC cells. SNHG6 overexpression promoted malignancy of EC and increased EC cell resistance to 5-FU. Besides, further molecular mechanism studies provided a novel regulatory pathways that SNHG6 knockdown promoted EC cell sensitivity to 5-FU by modulating STAT3 and H3K27me3 via promoting EZH2 expression.
化疗是食管癌（EC）患者的主要治疗方法。然而，由于多种因素导致的化疗耐药性是 EC 治疗的主要障碍。为了研究小核仁 RNA 宿主基因 6（SNHG6）如何影响 EC 中的 5-氟尿嘧啶（5-FU）耐药性及其可能的分子机制。本研究通过细胞活力测定、克隆形成、划痕试验和细胞凋亡评估 SNHG6 和增强子的作用Zeste 同源物 2（EZH2，组蛋白-赖氨酸 N-甲基转移酶）。通过 RT-qPCR 分析和 Western-blot（WB）检测确定了相关的分子机制。我们的数据表明，SNHG6 在 EC 细胞中的表达增加。SNHG6 促进集落形成和迁移，而抑制 EC 细胞凋亡。SNHG6 沉默显著促进了 KYSE150 和 KYSE450 细胞中 5-FU 的抑制作用。额外的机制研究表明，SNHG6 通过促进 EZH2 水平来调节 STAT3 和 H3K27me3。与 SNHG6 的功能相似，EZH2 的异常表达促进了 EC 的恶性程度，并加剧了其对 5-FU 的耐药性。此外，EZH2 的过表达消除了 SNHG6 沉默在 EC 细胞中对 5-FU 敏感性的作用。SNHG6 的过表达促进了 EC 的恶性程度，并增加了 EC 细胞对 5-FU 的耐药性。此外，进一步的分子机制研究提供了一条新的调控途径，即 SNHG6 敲低通过促进 EZH2 表达来调节 STAT3 和 H3K27me3，从而促进 EC 细胞对 5-FU 的敏感性。
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