Recent evidence revealed an inhibitory effect of circ-ITCH on the progression of papillary thyroid cancer via affecting the circ-ITCH/miR-22-3p/CBL axis. Rs4911154, an SNP located in circ-ITHC, was previously reported to be significantly associated with an increased risk of hepatocellular carcinoma. Ultrasound testing was used to evaluate the doubling time of thyroid nodules. 202 patients diagnosed with thyroid nodule disorders were divided into three groups according to their genotypes at rs4911154. We found that the A allele was correlated with a shortening doubling time of thyroid nodules. Moreover, the A allele contributed to reduced expression of circ-ITCH/CBL and increased expression of miR-22-3p. Besides, decreased tissue apoptosis was linked to the A allele. Luciferase assays indicated that miR-22-3p could effectively suppress the luciferase activities of CBL and circ-ITCH. Furthermore, manual up-regulation of miR-22-3p effectively suppressed the expression of CBL, while CBL siRNA apparently abolished circ-ITCH induced CBL upregulation, reduced proliferation and increased apoptosis of K1 and TPC-1 cells. A signaling pathway of circ-ITCH/miR-22-3p/CBL axis was established to explain the effect of SNP of circ-ITCH in thyroid tumor malignancy. Compared with the G allele, the A allele in rs4911154 contributed to the malignancy of thyroid nodules with decreased doubling time and down-regulated CBL expression.

最近的证据表明，circ-ITCH 通过影响 circ-ITCH/miR-22-3p/CBL 轴对甲状腺乳头状癌的进展具有抑制作用。Rs4911154 是一种位于 circ-ITHC 中的 SNP，之前有报道称其与肝细胞癌风险增加显着相关。超声检查用于评估甲状腺结节的倍增时间。根据rs4911154的基因型将202名诊断为甲状腺结节病的患者分为三组。我们发现 A 等位基因与甲状腺结节倍增时间缩短有关。此外，A 等位基因有助于降低 circ-ITCH/CBL 的表达并增加 miR-22-3p 的表达。此外，减少的组织凋亡与 A 等位基因有关。荧光素酶检测表明 miR-22-3p 可以有效抑制 CBL 和 circ-ITCH 的荧光素酶活性。此外，手动上调 miR-22-3p 有效抑制了 CBL 的表达，而 CBL siRNA 明显消除了 circ-ITCH 诱导的 CBL 上调，减少了 K1 和 TPC-1 细胞的增殖和凋亡。建立circ-ITCH/miR-22-3p/CBL轴信号通路来解释circ-ITCH的SNP在甲状腺肿瘤恶性肿瘤中的作用。与 G 等位基因相比，rs4911154 中的 A 等位基因导致甲状腺结节恶性，倍增时间缩短，CBL 表达下调。K1 和 TPC-1 细胞的增殖减少和凋亡增加。建立circ-ITCH/miR-22-3p/CBL轴信号通路来解释circ-ITCH的SNP在甲状腺肿瘤恶性肿瘤中的作用。与 G 等位基因相比，rs4911154 中的 A 等位基因导致甲状腺结节恶性，倍增时间缩短，CBL 表达下调。K1 和 TPC-1 细胞的增殖减少和凋亡增加。建立circ-ITCH/miR-22-3p/CBL轴信号通路来解释circ-ITCH的SNP在甲状腺肿瘤恶性肿瘤中的作用。与 G 等位基因相比，rs4911154 中的 A 等位基因导致甲状腺结节恶性，倍增时间缩短，CBL 表达下调。