目的:甲状腺乳头状癌(PTC)是甲状腺癌(THCA)最常见的亚型,内分泌系统中的一种恶性肿瘤。根据之前的研究,已发现神经细胞粘附分子(NRCAM)在PTC中上调并刺激PTC细胞的增殖和迁移。然而,NRCAM在PTC电池中的具体作用机制尚不完全清楚。因此,本研究旨在探讨NRCAM在PTC细胞中的作用机制,这些发现可以为PTC潜在治疗目标的开发提供新的见解。
结果:使用了生物信息学工具,并进行了一系列实验,包括蛋白质印迹,菌落形成,和双荧光素酶报告基因测定。收集的数据表明NRCAM在THCA组织和PTC细胞中过表达。发现环状RNANRCAM(circularRNANRCAM)在PTC细胞中高度表达,并积极调节NRCAM表达。通过功能丧失试验,circNRCAM和NRCAM都显示出促进增殖,入侵,和PTC细胞的迁移。机械上,这项研究证实,前体microRNA-506(pre-miR-506)可以与m6A去甲基酶AlkB同源物5(ALKBH5)结合,导致其M6A去甲基化。还发现circNRCAM可以竞争性结合ALKBH5,其抑制miR-506-3p表达并促进NRCAM表达。
结论:总之,circNRCAM可以通过下调miR-506-3p来上调NRCAM,从而增强PTC细胞的生物学行为。
OBJECTIVE: Papillary Thyroid Carcinoma (PTC) is the most prevalent subtype of Thyroid Carcinoma (THCA), a type of malignancy in the endocrine system. According to prior studies, Neural Cell Adhesion Molecule (NRCAM) has been found to be up-regulated in PTC and stimulates the proliferation and migration of PTC cells. However, the specific mechanism of NRCAM in PTC cells is not yet fully understood. Consequently, this study aimed to investigate the underlying mechanism of NRCAM in PTC cells, the findings of which could provide new insights for the development of potential treatment targets for PTC.
RESULTS: Bioinformatics tools were utilized and a series of experiments were conducted, including Western blot, colony formation, and dual-luciferase reporter assays. The data collected indicated that NRCAM was overexpressed in THCA tissues and PTC cells. Circular RNA NRCAM (
circNRCAM) was found to be highly expressed in PTC cells and to positively regulate NRCAM expression. Through loss-of-function assays, both
circNRCAM and NRCAM were shown to promote the proliferation, invasion, and migration of PTC cells. Mechanistically, this study confirmed that precursor microRNA-506 (pre-miR-506) could bind with m6A demethylase AlkB Homolog 5 (ALKBH5), leading to its m6A demethylation. It was also discovered that
circNRCAM could competitively bind to ALKBH5, which restrained miR-506-3p expression and promoted NRCAM expression.
CONCLUSIONS: In summary,
circNRCAM could up-regulate NRCAM by down-regulating miR-506-3p, thereby enhancing the biological behaviors of PTC cells.