PDF(Pubmed)
Abstract：
OBJECTIVE: Circular RNAs (circRNAs) are increasingly recognized for their important roles in various cancers, including papillary thyroid cancer (PTC). The specific mechanisms by which the circLIF receptor subunit alpha (circLIFR, hsa_circ_0072309) influences PTC progression remain largely unknown.
METHODS: In our study, CircLIFR, miR-429, and TIMP2 levels were assessed using reverse transcription-quantitative PCR. The roles of circLIFR and miR-429 in PTC cells were determined using Cell Counting Kit-8, colony formation, wound healing, and Transwell assays. Western blotting was utilized to examine the levels of TIMP2. The direct interaction between circLIFR, TIMP2, and miR-429 was confirmed using dual-luciferase reporter, RNA immunoprecipitation, and fluorescence in situ hybridization assays.
RESULTS: In PTC tissues and cells, a decrease in circLIFR and TIMP2 levels, accompanied by an increase in miR-429 levels, was observed. Overexpression of circLIFR or downregulation of miR-429 effectively suppressed the proliferation and migration of PTC cells. Conversely, the knockdown of circLIFR or overexpression of miR-429 had the opposite effect. Furthermore, circLIFR overexpression suppressed tumor growth in vivo. Mechanistically, circLIFR modulated TIMP2 expression by serving as a sponge for miR-429. Rescue experiments indicated that the antitumor effect of circLIFR could be reversed by miR-429.
CONCLUSIONS: This study confirmed circLIFR as a novel tumor suppressor delayed PTC progression through the miR-429/TIMP2 axis. These findings suggested that circLIFR held promise as a potential therapeutic target for PTC.
METHODS: In our study, CircLIFR, miR-429, and TIMP2 levels were assessed using reverse transcription-quantitative PCR. The roles of circLIFR and miR-429 in PTC cells were determined using Cell Counting Kit-8, colony formation, wound healing, and Transwell assays. Western blotting was utilized to examine the levels of TIMP2. The direct interaction between circLIFR, TIMP2, and miR-429 was confirmed using dual-luciferase reporter, RNA immunoprecipitation, and fluorescence in situ hybridization assays.
RESULTS: In PTC tissues and cells, a decrease in circLIFR and TIMP2 levels, accompanied by an increase in miR-429 levels, was observed. Overexpression of circLIFR or downregulation of miR-429 effectively suppressed the proliferation and migration of PTC cells. Conversely, the knockdown of circLIFR or overexpression of miR-429 had the opposite effect. Furthermore, circLIFR overexpression suppressed tumor growth in vivo. Mechanistically, circLIFR modulated TIMP2 expression by serving as a sponge for miR-429. Rescue experiments indicated that the antitumor effect of circLIFR could be reversed by miR-429.
CONCLUSIONS: This study confirmed circLIFR as a novel tumor suppressor delayed PTC progression through the miR-429/TIMP2 axis. These findings suggested that circLIFR held promise as a potential therapeutic target for PTC.
摘要：
目的：环状RNA（circularRNAs，circRNAs）在各种癌症中的重要作用日益得到认可，包括甲状腺乳头状癌（PTC）。circLIF受体亚基α(circLIFR，hsa_circ_0072309)对PTC进展的影响在很大程度上仍然未知。
方法：在我们的研究中，CircLIFR,使用逆转录-定量PCR评估miR-429和TIMP2水平。使用细胞计数试剂盒-8，集落形成，伤口愈合，和Transwell分析。使用Western印迹来检查TIMP2的水平。circLIFR之间的直接相互作用，使用双荧光素酶报告基因证实了TIMP2和miR-429，RNA免疫沉淀，和荧光原位杂交分析。
结果：在PTC组织和细胞中，CirlIFR和TIMP2水平的下降，伴随着miR-429水平的增加，被观察到。circLIFR的过表达或miR-429的下调有效抑制PTC细胞的增殖和迁移。相反，circLIFR的敲减或miR-429的过表达具有相反的作用.此外，circLIFR过表达抑制体内肿瘤生长。机械上,circLIFR通过充当miR-429的海绵来调节TIMP2表达。挽救实验表明，circLIFR的抗肿瘤作用可以被miR-429逆转。
结论：本研究证实circLIFR是一种新型肿瘤抑制因子，可通过miR-429/TIMP2轴延迟PTC进展。这些发现表明circLIFR有望成为PTC的潜在治疗靶标。
方法：在我们的研究中，CircLIFR,使用逆转录-定量PCR评估miR-429和TIMP2水平。使用细胞计数试剂盒-8，集落形成，伤口愈合，和Transwell分析。使用Western印迹来检查TIMP2的水平。circLIFR之间的直接相互作用，使用双荧光素酶报告基因证实了TIMP2和miR-429，RNA免疫沉淀，和荧光原位杂交分析。
结果：在PTC组织和细胞中，CirlIFR和TIMP2水平的下降，伴随着miR-429水平的增加，被观察到。circLIFR的过表达或miR-429的下调有效抑制PTC细胞的增殖和迁移。相反，circLIFR的敲减或miR-429的过表达具有相反的作用.此外，circLIFR过表达抑制体内肿瘤生长。机械上,circLIFR通过充当miR-429的海绵来调节TIMP2表达。挽救实验表明，circLIFR的抗肿瘤作用可以被miR-429逆转。
结论：本研究证实circLIFR是一种新型肿瘤抑制因子，可通过miR-429/TIMP2轴延迟PTC进展。这些发现表明circLIFR有望成为PTC的潜在治疗靶标。
