Chen Guo, Han Pengli, Zhang Qingsong, Li Mingchuang, Song Ting, Chen Zheng, Zhao Yatong, Yin Detao, Lv Jing
Department of Thyroid Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China.
Translational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China.
J Biochem Mol Toxicol. 2023 Dec;37(12):e23498. doi: 10.1002/jbt.23498. Epub 2023 Aug 11.
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.
环状RNA（circRNAs）已被发现与包括甲状腺乳头状癌（PTC）在内的多种癌症的发生和发展相关。据报道，circ_LDLR在PTC中高表达，但其潜在作用机制尚未完全阐明。本研究旨在探讨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和高迁移率族蛋白盒（HMGB）3的表达。采用CCK-8法和Transwell法评估细胞活力、侵袭和迁移能力。蛋白质免疫印迹法检测HMGB3蛋白表达。荧光素酶报告基因实验和下拉实验用于验证miR-1294与HMGB3或circ_LDLR之间的相互作用。circ_LDLR在PTC组织和细胞中高表达，敲低circ_LDLR可抑制PTC细胞的生长、侵袭和迁移。此外，miR-1294被认为是circ_LDLR的下游靶点，抑制miR-1294可部分逆转circ_LDLR敲低对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的下游靶点。我们的研究结果表明，circ_LDLR可能通过下调miR-1294和上调HMGB3表达在PTC中发挥促进作用。因此，circ_LDLR可能作为PTC的一个有价值的预后生物标志物和治疗靶点。
