Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. Deciphering the pathophysiological mechanisms that contribute to PTC development is essential to the discovery of optimal diagnostic and therapeutic approaches. MiR-146b-5p has been identified as a cancer-associated microRNA highly up-regulated in PTC. This study explores the hypothesis that miR-146b-5p contributes to papillary thyroid carcinogenesis through regulation of cell signaling pathways in a manner that overcomes the cellular growth suppressive events and provides survival advantage. The effect of miR-146b-5p inhibition on major cancer related signaling pathways and expression of Stanniocalcin-1 (STC1), an emerging molecule associated with stress response and carcinogenesis, was tested in cultured primary thyroid cells using luciferase reporter assays, quantitative real-time PCR, immunofluorescence staining, and flow cytometry. Our results demonstrated that miR-146b-5p inhibits the JNK/AP1 pathway activity and down-regulates the expression of STC-1 in thyroid-cultured cells and in thyroid tissue samples. In the presence of miR-146b-5p, PTC cells were resistant to cell death in response to oxidative stress. This is a novel report that miR-146b-5p directly targets STC1 and regulates the activity of JNK/AP1 pathway. Considering the importance of the JNK/AP1 pathway and STC1 in mediating many physiological and pathological processes like apoptosis, stress response and cellular metabolism, a biological regulator of these pathways would have a great scientific and clinical significance.

中文翻译：

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miR-146b-5p在甲状腺乳头状癌的发生过程中调节了应力激活的蛋白激酶途径和斯坦钙蛋白-1的表达。

甲状腺乳头状癌（PTC）是最常见的甲状腺癌类型。破解有助于PTC发展的病理生理机制对于发现最佳诊断和治疗方法至关重要。MiR-146b-5p已被鉴定为在PTC中高度上调的癌症相关microRNA。这项研究探索了一种假设，即miR-146b-5p通过克服细胞生长抑制事件并提供生存优势的方式，通过调节细胞信号通路来促进甲状腺乳头状癌的发生。使用萤光素酶报告基因测定法在培养的原代甲状腺细胞中测试了miR-146b-5p抑制对主要癌症相关信号通路和与压力反应和致癌作用相关的新兴分子斯坦尼古斯丁-1（STC1）表达的影响，实时定量PCR，免疫荧光染色和流式细胞仪。我们的结果表明，miR-146b-5p抑制了JNK / AP1途径的活性，并下调了甲状腺培养细胞和甲状腺组织样品中STC-1的表达。在miR-146b-5p存在的情况下，PTC细胞对细胞死亡具有抗性，可响应氧化应激。这是一个新颖的报道，miR-146b-5p直接靶向STC1并调节JNK / AP1途径的活性。考虑到JNK / AP1途径和STC1在介导许多生理和病理过程（如凋亡，应激反应和细胞代谢）中的重要性，这些途径的生物调节剂将具有重大的科学和临床意义。我们的结果表明，miR-146b-5p抑制了JNK / AP1途径的活性，并下调了甲状腺培养细胞和甲状腺组织样品中STC-1的表达。在miR-146b-5p存在的情况下，PTC细胞对细胞死亡具有抗性，可响应氧化应激。这是一个新颖的报道，miR-146b-5p直接靶向STC1并调节JNK / AP1途径的活性。考虑到JNK / AP1途径和STC1在介导许多生理和病理过程（如凋亡，应激反应和细胞代谢）中的重要性，这些途径的生物调节剂将具有重大的科学和临床意义。我们的结果证明，miR-146b-5p抑制JNK / AP1途径的活性并下调甲状腺培养细胞和甲状腺组织样品中STC-1的表达。在miR-146b-5p存在的情况下，PTC细胞对细胞死亡具有抗性，可响应氧化应激。这是一个新颖的报道，miR-146b-5p直接靶向STC1并调节JNK / AP1途径的活性。考虑到JNK / AP1途径和STC1在介导许多生理和病理过程（如凋亡，应激反应和细胞代谢）中的重要性，这些途径的生物调节剂将具有重大的科学和临床意义。PTC细胞对细胞的死亡具有抵抗力，可以抵抗氧化应激。这是一个新颖的报道，miR-146b-5p直接靶向STC1并调节JNK / AP1途径的活性。考虑到JNK / AP1途径和STC1在介导许多生理和病理过程（如凋亡，应激反应和细胞代谢）中的重要性，这些途径的生物调节剂将具有重大的科学和临床意义。PTC细胞对细胞的死亡具有抵抗力，可以抵抗氧化应激。这是一个新颖的报道，miR-146b-5p直接靶向STC1并调节JNK / AP1途径的活性。考虑到JNK / AP1途径和STC1在介导许多生理和病理过程（如凋亡，应激反应和细胞代谢）中的重要性，这些途径的生物调节剂将具有重大的科学和临床意义。