Department of Otolarynology, Wuhan No.1.Hospital, Wuhan 430030, China.
General Surgery, Wuhan Hanyang Hospital, Wuhan 430000, China.
Dis Markers. 2021 Dec 9;2021:3977189. doi: 10.1155/2021/3977189. eCollection 2021.
Circular RNAs (circRNAs) have been reported to play important roles in the development and progression of papillary thyroid carcinoma (PTC). However, the function and molecular mechanism of circRNA low-density lipoprotein receptor (circLDLR) in the tumorigenesis of PTC remain unknown.
In this study, circLDLR was found to be markedly upregulated in PTC tissues and cell lines, and knockdown of circLDLR inhibited PTC cell proliferation, migration, and invasion but induced apoptosis . Moreover, circLDLR acted as a sponge for miR-637, and miR-637 interference reversed the anticancer effects of circLDLR knockdown on PTC cells. LMO4 was verified to be a target of miR-637; LMO4 upregulation abolished miR-637 mediated inhibition of cell growth and metastasis in PTC. Additionally, circLDLR could indirectly modulate LMO4 via acting as a sponge of miR-637 in PTC cells. Besides that, xenograft analysis showed that circLDLR knockdown suppressed tumor growth via regulating LMO4 and miR-637.
Taken together, these results demonstrated that circLDLR promoted PTC tumorigenesis through miR-637/LMO4 axis, which may provide a novel insight into the understanding of PTC tumorigenesis and be useful in developing potential targets for PTC treatment.
环状 RNA(circRNAs)已被报道在甲状腺乳头状癌(PTC)的发生发展中发挥重要作用。然而,circRNA 低密度脂蛋白受体(circLDLR)在 PTC 肿瘤发生中的功能和分子机制尚不清楚。
本研究发现,circLDLR 在 PTC 组织和细胞系中明显上调,circLDLR 敲低抑制 PTC 细胞增殖、迁移和侵袭,但诱导细胞凋亡。此外,circLDLR 可作为 miR-637 的海绵体,而 miR-637 干扰逆转了 circLDLR 敲低对 PTC 细胞的抗癌作用。LMO4 被验证为 miR-637 的靶标;LMO4 的上调消除了 miR-637 介导的对 PTC 细胞生长和转移的抑制作用。此外,circLDLR 可通过在 PTC 细胞中作为 miR-637 的海绵体间接调节 LMO4。此外,异种移植分析表明,circLDLR 敲低通过调节 LMO4 和 miR-637 抑制肿瘤生长。
综上所述,这些结果表明,circLDLR 通过 miR-637/LMO4 轴促进 PTC 肿瘤发生,这可能为理解 PTC 肿瘤发生提供新的见解,并有助于开发 PTC 治疗的潜在靶点。