Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Xingxiang Medical University, Weihui, Henan, China.
Department of Operating Room, The First Affiliated Hospital of Xingxiang Medical University, Weihui, Henan, China.
Neoplasma. 2022 Jan;69(1):1-15. doi: 10.4149/neo_2021_210608N771. Epub 2021 Oct 26.
Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer (TC). There is increasing evidence that circular RNAs play a role in the tumorigenesis of PTC. The aim of our study was to evaluate the potential function of circ_0067934 in PTC and the underlying molecular mechanism. In our study, cell viability assay, quantitative real-time PCR (qRT-PCR), colony formation assay, flow cytometry, wound-healing assay, Transwell invasion assay, western blot, soft agar assay, RNA immunoprecipitation (RIP), dual-luciferase reporter assay, immunohistochemical (IHC) staining, and tumor xenograft formation were conducted to evaluate the effects of circ_0067934 in PTC cells. We found that circ_0067934 was upregulated in PTC tissues and cell lines. Knockdown of circ_0067934 inhibited growth, colony formation, migration, invasion, EMT, and tumor xenograft growth, and induced apoptosis of PTC cells. Moreover, circ_0067934 acted as a molecular sponge for miR-1301-3p, and depletion of miR-1301-3p abrogated the effects of circ_0067934 knockdown in PTC cells. In addition, HMGB1 was a target of miR-1301-3p, and miR-1301-3p overexpression inhibited the malignant effects of PTC cells via suppressing HMGB1. Furthermore, knockdown of circ_0067934 suppressed HMGB1 expression, PI3K/Akt, and MAPK activation by sponging miR-1301-3p. In nude mice, circ_0067934 depletion repressed tumor xenograft growth of PTC cells. In conclusion, our results provided a novel insight into circ_0067934 in the tumorigenesis and progression of PTC. circ_0067934 might be a prognostic marker or therapeutic target for PTC treatment.
甲状腺癌(TC)中最常见的类型是甲状腺乳头状癌(PTC)。越来越多的证据表明,环状 RNA 在 PTC 的肿瘤发生中发挥作用。本研究旨在评估 circ_0067934 在 PTC 中的潜在功能及其潜在的分子机制。在我们的研究中,通过细胞活力测定、实时定量 PCR(qRT-PCR)、集落形成测定、流式细胞术、划痕愈合测定、Transwell 侵袭测定、Western blot、软琼脂测定、RNA 免疫沉淀(RIP)、双荧光素酶报告基因测定、免疫组织化学(IHC)染色和肿瘤异种移植形成实验来评估 circ_0067934 在 PTC 细胞中的作用。我们发现,circ_0067934 在 PTC 组织和细胞系中上调。circ_0067934 敲低抑制了 PTC 细胞的生长、集落形成、迁移、侵袭、上皮间质转化和肿瘤异种移植生长,并诱导 PTC 细胞凋亡。此外,circ_0067934 作为 miR-1301-3p 的分子海绵,并且 miR-1301-3p 的耗竭消除了 circ_0067934 敲低在 PTC 细胞中的作用。此外,HMGB1 是 miR-1301-3p 的靶标,并且 miR-1301-3p 通过抑制 HMGB1 过表达抑制了 PTC 细胞的恶性作用。此外,circ_0067934 的敲低通过海绵 miR-1301-3p 抑制 HMGB1 的表达、PI3K/Akt 和 MAPK 激活。在裸鼠中,circ_0067934 耗竭抑制了 PTC 细胞的肿瘤异种移植生长。总之,我们的结果为 circ_0067934 在 PTC 的肿瘤发生和进展中提供了新的见解。circ_0067934 可能是 PTC 治疗的预后标志物或治疗靶点。