Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, 710061, China.
Department of Gynecology and Obstetrics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
J Ovarian Res. 2020 Dec 10;13(1):144. doi: 10.1186/s13048-020-00750-4.
This study aimed to explore whether the dysregulation of lnc-small nucleolar RNA host gene 1 (SNHG1) and miR-216b-5p correlated with chemoresistance and indicated poor prognosis of serous epithelial ovarian cancer (EOC).
The expression of lnc-SNHG1 was upregulated, while miR-216b-5p showed low expression in patients with chemoresistant EOC compared with patients with chemosensitive EOC. The multivariate Cox regression analysis showed that the expression of miR-216b-5p and FIGO stage were independent prognostic factors for the overall survival (OS) of patients with serous EOC. Kaplan-Meier curves revealed a significant association of the increased expression level of lnc-SNHG1 with shorter OS and disease-free survival (DFS). Patients with a low expression level of miR-216b-5p also had shorter OS and DFS. The biological functions were tested using CCK-8 assay, colony formation assay, wound healing assay, and cell apoptosis. The knockdown of SNHG1 and the overexpression of miR-216b-5p stimulated paclitaxel sensitivity in A2780/Taxol cells through inhibiting cell growth and migration and promoting apoptosis. The inhibition of miR-216b-5p could rescue the effect of lnc-SNHG1 inhibition on the sensitivity of A2780/Taxol cells to paclitaxel. Luciferase reporter assay, RNA Binding Protein Immunoprecipitation Assay (RIP), and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) indicated that lnc-SNHG1 acted as a sponge of miR-216b-5p in A2780/Taxol cells.
This study showed that the overexpression of lnc-SNHG1 and decreased expression level of miR-216b-5p correlated with the chemoresistance of patients with serous EOC and indicated shorter OS and DFS. Lnc-SNHG1 functioned as a ceRNA with miR-216b-5p, which was critical in modulating the paclitaxel sensitivity of ovarian cancer cells.
本研究旨在探讨长链非编码 RNA 小核仁 RNA 宿主基因 1（SNHG1）和 miR-216b-5p 的失调是否与上皮性卵巢癌（EOC）的化疗耐药相关，并提示预后不良。
与化疗敏感的 EOC 患者相比，化疗耐药的 EOC 患者中 lnc-SNHG1 的表达上调，而 miR-216b-5p 的表达水平较低。多变量 Cox 回归分析显示，miR-216b-5p 的表达和FIGO 分期是影响浆液性 EOC 患者总生存期（OS）的独立预后因素。Kaplan-Meier 曲线显示，lnc-SNHG1 表达水平升高与 OS 和无病生存期（DFS）较短显著相关。miR-216b-5p 低表达的患者 OS 和 DFS 也较短。通过 CCK-8 测定、集落形成测定、划痕愈合测定和细胞凋亡测定来测试生物学功能。敲低 SNHG1 和过表达 miR-216b-5p 通过抑制细胞生长和迁移以及促进细胞凋亡来刺激 A2780/Taxol 细胞对紫杉醇的敏感性。抑制 miR-216b-5p 可挽救 lnc-SNHG1 抑制对 A2780/Taxol 细胞对紫杉醇敏感性的影响。荧光素酶报告测定、RNA 结合蛋白免疫沉淀测定（RIP）和定量逆转录聚合酶链反应（qRT-PCR）表明，lnc-SNHG1 在 A2780/Taxol 细胞中作为 miR-216b-5p 的海绵。
本研究表明，lnc-SNHG1 的过表达和 miR-216b-5p 的表达水平降低与浆液性 EOC 患者的化疗耐药相关，并提示 OS 和 DFS 较短。lnc-SNHG1 作为 ceRNA 与 miR-216b-5p 相互作用，这在调节卵巢癌细胞对紫杉醇的敏感性中起关键作用。
