Liver Research Center, Chang Gung Memorial Hospital, 15 Wen-hwa 1 Road, Linkou, Taoyuan 333, Taiwan.
Department of Biochemistry, College of Medicine, Chang Gung University, 259 Wen-hwa 1 Road, Taoyuan 333, Taiwan.
Cells. 2020 Jan 21;9(2):262. doi: 10.3390/cells9020262.
Thyroid hormone (T) and its receptor (TR) are involved in cell metabolism and cancer progression. Hypothyroidism is associated with significantly elevated risk of hepatocellular carcinoma (HCC). Levels of the glycoprotein alpha-fetoprotein (AFP) are increased in the majority of patients with HCC and may be useful in diagnosis and follow-up. However, the relationship between T/TR and AFP levels in HCC is currently unclear. The expression profiles of long non-coding RNAs (lncRNAs) were compared in microarrays of HepG2-TRα1 cells treated with/without T and HCC specimens. The effects of T on taurine upregulated gene 1 () and expression were validated using qRT-PCR. A correlation between TUG1 and AFP was confirmed via RNAi and clustered regularly interspaced short palindromic repeats (CRISPR) strategies. Finally, overall and recurrence-free survival rates were analyzed using the Kaplan-Meier method and confirmed in online datasets. T/TR treatment reduced expression in vitro, resulting in the downregulation of mRNA. Knockdown of suppressed cell cycle progression and soft agar colony formation and induced cellular senescence. Our data support the involvement of TUG1 in the T/TR-mediated suppression of cell growth. mRNA levels showed strong positive correlations with TUG1 and unfavorable prognosis in patients with non-hepatitis B/non-hepatitis C HCC (NBNC-HCC). T/TR, TUG1, and AFP may potentially serve as effective prognostic markers for NBNC-HCC.
甲状腺激素（T）及其受体（TR）参与细胞代谢和癌症进展。甲状腺功能减退症与肝细胞癌（HCC）的风险显著升高有关。大多数 HCC 患者的糖蛋白甲胎蛋白（AFP）水平升高，在诊断和随访中可能有用。然而，T/TR 和 AFP 水平在 HCC 中的关系尚不清楚。通过对用 T 处理/未处理的 HepG2-TRα1 细胞的微阵列和 HCC 标本进行比较，得出长链非编码 RNA（lncRNA）的表达谱。使用 qRT-PCR 验证 T 对牛磺酸上调基因 1（）和表达的影响。通过 RNAi 和规律间隔短回文重复（CRISPR）策略证实 TUG1 与 AFP 之间存在相关性。最后，使用 Kaplan-Meier 方法分析总生存率和无复发生存率，并在在线数据集中进行验证。T/TR 处理体外降低了的表达，导致 mRNA 的下调。抑制的表达抑制细胞周期进展和软琼脂集落形成，并诱导细胞衰老。我们的数据支持 TUG1 在 T/TR 介导的细胞生长抑制中的作用。mRNA 水平与 TUG1 呈强烈正相关，与非乙型肝炎/非丙型肝炎 HCC（NBNC-HCC）患者的不良预后相关。T/TR、TUG1 和 AFP 可能是 NBNC-HCC 的有效预后标志物。
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