循环_LDLR 通过调节 miR-1294/HMGB3 轴促进乳头状甲状腺癌的进展。
Circ_LDLR promotes the progression of papillary thyroid carcinoma by regulating miR-1294/HMGB3 axis.
发表日期:2023 Aug 11
作者:
Guo Chen, Pengli Han, Qingsong Zhang, Mingchuang Li, Ting Song, Zheng Chen, Yatong Zhao, Detao Yin, Jing Lv
来源:
Cellular & Molecular Immunology
摘要:
循环RNA(circRNAs)已被发现与包括乳头状甲状腺癌(PTC)在内的癌症的发展和进展相关。已报道 circ_LDLR 在 PTC 中高表达,但其作用机制尚未完全阐明。本研究旨在调查 circ_LDLR 在 PTC 中的作用。通过定量实时聚合酶链反应(qRT-PCR)检测 circ_LDLR、miR-1294 和高迁移率族群盒(HMGB)3 的表达。采用 CCK-8 实验和 Transwell 实验评估细胞存活能力、侵袭能力和迁移能力。采用蛋白质印迹实验检测 HMGB3 蛋白的表达水平。采用荧光素酶报告基因和下拉实验验证 miR-1294 与 HMGB3 或 circ_LDLR 之间的相互作用。circ_LDLR 在 PTC 组织和细胞中表达水平较高,其敲除抑制了 PTC 细胞的生长、侵袭和迁移。此外,miR-1294 被认为是 circ_LDLR 的下游靶标,并且 miR-1294 的抑制部分逆转了对 PTC 细胞生长、侵袭和迁移的抑制作用。更重要的是,HMGB3 被鉴定为 miR-1294 的下游靶标。我们的发现表明 circ_LDLR 可能通过下调 miR-1294 和上调 HMGB3 的表达在 PTC 中起到促进作用。因此,circ_LDLR 可能作为 PTC 的有价值的预后生物标记物和治疗靶点。© 2023 Waverly Periodicals LLC.
Circular RNAs (circRNAs) have been found to be associated with the development and progression of cancers including papillary thyroid carcinoma (PTC). Circ_LDLR has been reported to be highly expressed in PTC, but its underlying mechanism of action has not been fully elucidated. This study aimed to investigate the role of circ_LDLR in PTC. The expression of circ_LDLR, miR-1294 and high mobility group box (HMGB) 3 was detected by quantitative real-time polymerase chain reaction (qRT-PCR). CCK-8 assay and transwell assays were employed to value cell viability, invasion and migration abilities. Western blot assay was to detect HMGB3 protein expression. Luciferase reporter gene and pull down assay were used to validate the interaction between miR-1294 and HMGB3 or circ_LDLR. Circ_LDLR showed high expression levels in PTC tissues and cells and knockdown of it inhibited the growth, invasion, and migration of PTC cells. In addition, miR-1294 was considered as a downstream target of circ_LDLR, and inhibition of miR-1294 partially reversed the inhibitory effects of circ_LDLR knockdown on PTC cells growth, invasion, and migration. More importantly, HMGB3 was identified as a downstream target of miR-1294. Our findings suggest circ_LDLR may plays a promoting role in PTC by downregulating miR-1294 and upregulating HMGB3 expression. Therefore, circ_LDLR may serve as a valuable prognostic biomarker and therapeutic target for PTC.© 2023 Wiley Periodicals LLC.