Duan Yu, Wang Zhiyong, Xu Lijuan, Sun Li, Song Hairong, Yin Huiqing, He Fucheng
Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China.
Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China.
J Cancer. 2020 Mar 15;11(12):3492-3501. doi: 10.7150/jca.42070. eCollection 2020.
The incidence of papillary thyroid carcinoma (PTC) has been increased rapidly in recent decades. Long noncoding RNAs (lncRNA) are a class of non-protein-coding transcripts and play critical roles in regulating gene expression and influence biological behaviors of multiple cancers, including PTC. Here, we discovered that lncRNA SNHG3 was significantly downregulated in PTC tissues and cell lines, the expression of SNHG3 was negatively correlated with the TNM stage and poor prognosis of PTC patients. Functional studies illustrated that the depletion of SNHG3 via CRISPR/Cas9 technology promoted the proliferation, migration and invasion abilities of PTC cells. Tumor xenograft models confirmed the tumor-promoting role of silenced SNHG3 . Further mechanistic analyses revealed that knockout of SNHG3 activated the AKT/mTOR/ERK pathway in PTC cell lines and the mTOR inhibitor AZD8055 abrogated the tumor-promoting effect induced by SNHG3 inhibition. Taken together, our findings identified a lncRNA SNHG3 that functions its tumor-suppressor role during PTC development and SNHG3 might serve as a promising candidate for target therapy of PTC.
近几十年来，甲状腺乳头状癌（PTC）的发病率迅速上升。长链非编码RNA（lncRNA）是一类非蛋白质编码转录本，在调节基因表达以及影响包括PTC在内的多种癌症的生物学行为中发挥着关键作用。在此，我们发现lncRNA SNHG3在PTC组织和细胞系中显著下调，SNHG3的表达与PTC患者的TNM分期及不良预后呈负相关。功能研究表明，通过CRISPR/Cas9技术敲低SNHG3可促进PTC细胞的增殖、迁移和侵袭能力。肿瘤异种移植模型证实了沉默SNHG3的促肿瘤作用。进一步的机制分析显示，敲除SNHG3可激活PTC细胞系中的AKT/mTOR/ERK通路，而mTOR抑制剂AZD8055可消除SNHG3抑制所诱导的促肿瘤效应。综上所述，我们的研究结果确定了一种lncRNA SNHG3，其在PTC发生发展过程中发挥肿瘤抑制作用，SNHG3可能是PTC靶向治疗的一个有前景的候选靶点。
