背景:长链非编码RNA(lncRNAs)在肿瘤发病机制中起着至关重要的作用。然而,大多数这些基因的功能仍不清楚。在本研究中,我们旨在揭示LINC01176在甲状腺癌中的作用。
方法:应用Western印迹和qRT-PCR分析LINC01176,miR-146b-5p,和SH3GL相互作用内吞接头1(SGIP1)。使用CCK-8测定和伤口愈合实验评估了增殖和迁移能力,分别。通过蛋白质印迹定量凋亡相关标志物Bcl-2和Bax来研究细胞的凋亡。使用裸鼠建立动物模型以确定LINC01176在肿瘤发生中的作用。使用双荧光素酶报告基因和RIP分析验证了MiR-146b-5p与LINC01176和SGIP1的推定结合。
结果:LINC01176在甲状腺癌细胞系和组织中表达下调。LINC01176过表达抑制癌细胞增殖和迁移,但诱导细胞凋亡。升高的LINC01176表达阻碍动物模型中的肿瘤发生。LINC01176靶向miR-146b-5p并负调控其表达。miR-146b-5p的富集抵消了LINC01176过表达的功能效应。此外,miR-146b-5p与SGIP1相互作用并负调控其表达。因此,miR-146b-5p减弱SGIP1的抗癌作用。
结论:LINC01176负调控miR-146b-5p表达并上调SGIP1表达。因此,LINC01176阻断甲状腺癌的恶性进展。
BACKGROUND: Long non-coding RNA (lncRNAs) plays a crucial role in tumor pathogenesis. However, the function of most of these genes remains unclear.
OBJECTIVE: In the present study, we aimed to unveil LINC01176\'s role in thyroid cancer.
METHODS: Western blotting and qRT-PCR were applied for the analysis of the expressions of LINC01176, miR-146b-5p, and SH3GL interacting endocytic adaptor 1 (
SGIP1). Proliferative and migratory capabilities were assessed using the CCK-8 assay and wound-healing experiments, respectively. Apoptosis of the cells was studied by quantifying the apoptosis-related markers Bcl-2 and Bax by western blotting. Animal models were established using nude mice to determine the role of LINC01176 in tumorigenesis. MiR-146b-5p\'s putative binding to LINC01176 and
SGIP1 was validated using dual-luciferase reporter and RIP analyses.
RESULTS: LINC01176 expression was downregulated in the thyroid cancer cell lines and tissues. LINC01176 overexpression represses cancer cell proliferation and migration but induces apoptosis. Elevated LINC01176 expression hampers tumorigenesis in animal models. LINC01176 targeted miR-146b-5p and negatively regulated its expression. Enrichment of miR-146b-5p counteracted the functional effects of LINC01176 overexpression. Additionally, miR-146b-5p interacted with
SGIP1 and negatively regulated its expression. Thus, miR-146b-5p attenuates the anti-cancer effects of
SGIP1.
CONCLUSIONS: LINC01176 negatively regulates the expression miR-146b-5p and upregulates
SGIP1 expression. Hence, LINC01176 blocks the malignant progression of thyroid cancer.