Hou Shasha, Xie Xiaorui, Zhao Jing, Wu Cailan, Li Ning, Meng Zhaowei, Cai Chunquan, Tan Jian
Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, China.
Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin, China.
Front Oncol. 2021 Jan 8;10:566365. doi: 10.3389/fonc.2020.566365. eCollection 2020.
The dedifferentiation of differentiated thyroid cancer (DTC) is a challenging problem for radioactive iodine (I) treatment, also known as radioiodine refractory differentiated thyroid cancer (RAIR-DTC). The purpose of this study was to further explore the mechanism of the redifferentiation of dedifferentiated thyroid cancer. Ineffective and effective groups of I therapy were analyzed and compared in both our clinical and TCGA samples. Whole-exome sequencing, mutation analysis, transcriptome analysis, and functional experiments were conducted. , , , , and were overlapping mutation genes between our clinical cases, and the TCGA cases only appeared in the ineffective group. The expression of target was explored. The expression levels of and were significantly increased, and the inhibition of expression significantly inhibited proliferation and migration, promoted apoptosis, regulated the expression and location of thyroid differentiation-related genes, and sodium/iodide symporter (NIS) in dedifferentiated thyroid cancer cells (WRO). Thus, potentially targets participation in the formation of DTC dedifferentiation, resulting in resistance to I and the loss of the iodine uptake ability of DTC cancer foci, promoting refractory differentiated thyroid cancer. may be a potentially therapeutic target for the reapplication of I therapy in dedifferentiated thyroid cancer patients.
分化型甲状腺癌（DTC）的去分化是放射性碘（I）治疗面临的一个具有挑战性的问题，也被称为放射性碘难治性分化型甲状腺癌（RAIR-DTC）。本研究的目的是进一步探究去分化型甲状腺癌再分化的机制。对我们的临床样本和TCGA样本中的I治疗无效组和有效组进行了分析和比较。进行了全外显子测序、突变分析、转录组分析和功能实验。 、 、 、 、 是我们临床病例之间的重叠突变基因，而这些基因在TCGA病例中仅出现在无效组。探究了 靶点的表达情况。 及 的表达水平显著升高，抑制 表达可显著抑制去分化型甲状腺癌细胞（WRO）的增殖和迁移，促进细胞凋亡，调节甲状腺分化相关基因及钠/碘同向转运体（NIS）的表达和定位。因此， 可能靶向参与DTC去分化的形成，导致对I产生抗性以及DTC癌灶碘摄取能力丧失，促使分化型甲状腺癌难治。 可能是去分化型甲状腺癌患者重新应用I治疗的一个潜在治疗靶点。
