Department of Thyroid-Head and Neck Surgery, Jilin Cancer Hospital, Changchun, Jilin, P.R. China.
Cell Cycle. 2020 May;19(10):1186-1199. doi: 10.1080/15384101.2020.1749466. Epub 2020 Apr 19.
Long noncoding RNA termed small nucleolar RNA host gene 22 (SNHG22) is a crucial regulator in epithelial ovarian carcinoma. Nevertheless, the regulatory functions of SNHG22 in papillary thyroid cancer (PTC) progression and its mechanisms of action remain poorly defined. Therefore, the present study aimed to investigate the role of SNHG22 in the malignant phenotype of PTC and determine whether SNHG22 regulates PTC progression via a ceRNA mechanism. SNHG22 expression in PTC was detected using reverse transcription-quantitative polymerase chain reaction analysis. The biological actions of SNHG22 silencing in PTC cells were evaluated both in vitro (using Cell Counting Kit-8 assay, flow cytometry analysis, and cell migration and invasion assays) and in vivo (using tumorigenicity assay). Herein, high SNHG22 expression was observed in PTC tissues and cell lines. This high SNHG22 level was closely associated with unfavorable clinicopathological characteristics and worse overall survival in patients with PTC. SNHG22 knockdown effectively suppressed PTC cell proliferation, migration, and invasion in vitro; accelerated cell apoptosis; and hindered tumor growth in vivo. Mechanistic experiments revealed that SNHG22 directly interacts with microRNA-429 (miR-429) as an miRNA sponge and positively modulates ZEB1 expression. Rescue assays found that miR-429 inhibition or ZEB1 upregulation can offset the actions of SNHG22 knockdown in PTC cells. In sum, SNHG22, miR-429, and ZEB1 form an interactive regulatory network with cancer-promoting roles in PTC cells, suggesting that the SNHG22/miR-429/ZEB1 pathway is a novel diagnostic and therapeutic target.
长链非编码 RNA 称为小核仁 RNA 宿主基因 22(SNHG22)是上皮性卵巢癌的关键调节因子。然而,SNHG22 在甲状腺乳头状癌(PTC)进展中的调节功能及其作用机制仍未明确。因此,本研究旨在探讨 SNHG22 在 PTC 恶性表型中的作用,并确定 SNHG22 是否通过 ceRNA 机制调节 PTC 进展。采用逆转录-定量聚合酶链反应分析检测 PTC 中 SNHG22 的表达。在体外(使用细胞计数试剂盒-8 分析、流式细胞术分析、细胞迁移和侵袭分析)和体内(使用致瘤性分析)评估 SNHG22 沉默对 PTC 细胞的生物学作用。结果显示,PTC 组织和细胞系中 SNHG22 表达升高。这种高水平的 SNHG22 与 PTC 患者不良的临床病理特征和更差的总生存期密切相关。SNHG22 敲低可有效抑制 PTC 细胞在体外的增殖、迁移和侵袭;加速细胞凋亡;并抑制体内肿瘤生长。机制实验表明,SNHG22 作为 miRNA 海绵直接与 microRNA-429(miR-429)相互作用,正向调节 ZEB1 表达。挽救实验发现,miR-429 抑制或 ZEB1 上调可抵消 SNHG22 敲低对 PTC 细胞的作用。总之,SNHG22、miR-429 和 ZEB1 在 PTC 细胞中形成具有促癌作用的相互作用调控网络,提示 SNHG22/miR-429/ZEB1 通路是 PTC 的一种新的诊断和治疗靶点。