Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
Department of Thyroid and Breast Surgery, Suqian Hospital Affiliated to Xuzhou Medical University, Suqian, China.
Cell Prolif. 2019 May;52(3):e12564. doi: 10.1111/cpr.12564. Epub 2019 Apr 1.
Thyroid carcinoma (TC) represents a malignant neoplasm affecting the thyroid. Current treatment strategies include the removal of part of the thyroid; however, this approach is associated with a significant risk of developing hypothyroidism. In order to adequately understand the expression profiles of TNRC6C-AS1 and STK4 and their potential functions in TC, an investigation into their involvement with Hippo signalling pathway and the mechanism by which they influence TC apoptosis and autophagy were conducted.
A microarray analysis was performed to screen differentially expressed lncRNAs associated with TC. TC cells were employed to evaluate the role of TNRC6C-AS1 by over-expression or silencing means. The interaction of TNRC6C-AS1 with methylation of STK4 promoter was evaluated to elucidate its ability to elicit autophagy, proliferation and apoptosis.
TNRC6C-AS1 was up-regulated while STK4 was down-regulated, where methylation level was elevated. STK4 was verified as a target gene of TNRC6C-AS1, which was enriched by methyltransferase. Methyltransferase's binding to STK4 increased expression of its promoter. Over-expressed TNRC6C-AS1 inhibited STK4 by promoting STK4 methylation and reducing the total protein levels of MST1 and LATS1/2. The phosphorylation of YAP1 phosphorylation was decreased, which resulted in the promotion of SW579 cell proliferation and tumorigenicity.
Based on our observations, we subsequently confirmed the anti-proliferative, pro-apoptotic and pro-autophagy capabilities of TNRC6C-AS1 through STK4 methylation via the Hippo signalling pathway in TC.
甲状腺癌（TC）是一种影响甲状腺的恶性肿瘤。目前的治疗策略包括切除部分甲状腺；然而，这种方法与发生甲状腺功能减退的风险显著相关。为了充分了解 TNRC6C-AS1 和 STK4 的表达谱及其在 TC 中的潜在功能，研究了它们与 Hippo 信号通路的关系，以及它们影响 TC 细胞凋亡和自噬的机制。
进行了微阵列分析，以筛选与 TC 相关的差异表达 lncRNA。使用 TC 细胞通过过表达或沉默手段来评估 TNRC6C-AS1 的作用。评估了 TNRC6C-AS1 与 STK4 启动子甲基化的相互作用，以阐明其诱导自噬、增殖和凋亡的能力。
TNRC6C-AS1 上调，而 STK4 下调，甲基化水平升高。验证 STK4 是 TNRC6C-AS1 的靶基因，被甲基转移酶富集。甲基转移酶与 STK4 的结合增加了其启动子的表达。过表达的 TNRC6C-AS1 通过促进 STK4 甲基化和降低 MST1 和 LATS1/2 的总蛋白水平来抑制 STK4。YAP1 磷酸化减少，促进 SW579 细胞增殖和致瘤性。
基于我们的观察结果，我们随后通过 Hippo 信号通路证实了 TNRC6C-AS1 通过 STK4 甲基化在 TC 中具有抗增殖、促凋亡和促自噬的能力。
