Department of Thyroid Surgery, The First Hospital of China Medical University, 155 Nanjing Bei Street, Shenyang, Liaoning Province, 110001, People's Republic of China.
Cell Death Dis. 2022 Mar 25;13(3):270. doi: 10.1038/s41419-022-04728-6.
Papillary thyroid carcinoma (PTC) is the main type of thyroid carcinoma. Despite the good prognosis, some PTC patients may deteriorate into more aggressive diseases, leading to poor survival. Molecular technology has been increasingly used in the diagnosis and treatment of thyroid carcinoma. In this study, we identified that RNA Binding Motif Protein 47 (RBM47) was downregulated in PTC tissues and cells, and overexpression of RBM47 could activate autophagy and inhibit proliferation in PTC cells. RBM47 promotes but can not bind directly to Forkhead Box O3 (FOXO3). FOXO3 activates Autophagy Related Gene 3 (ATG3), ATG5, and RBM47 to form a loop and promote autophagy. RBM47 can bind directly to and stabilized lncRNA Small Nucleolar RNA Host Gene 5 (SNHG5) to inhibit PTC cells proliferation and activate autophagy in vitro and in vivo. SNHG5 inhibits ubiquitination and degradation of FOXO3 by recruiting Ubiquitin Specific Peptidase 21 (USP21), then promotes the translocation of FOXO3 from cytoplasm to nucleus. Our study revealed the regulatory mechanism of RBM47/SNHG5/FOXO3 axis on cell proliferation and autophagy in PTC, which may provide valuable insight for the treatment of PTC.
甲状腺癌（PTC）是甲状腺癌的主要类型。尽管预后良好，但一些 PTC 患者可能恶化成更具侵袭性的疾病，导致生存状况不佳。分子技术已越来越多地应用于甲状腺癌的诊断和治疗。在本研究中，我们发现 RNA 结合基序蛋白 47（RBM47）在 PTC 组织和细胞中表达下调，过表达 RBM47 可激活自噬并抑制 PTC 细胞增殖。RBM47 促进但不能直接与叉头框蛋白 O3（FOXO3）结合。FOXO3 激活自噬相关基因 3（ATG3）、ATG5 和 RBM47 形成环，促进自噬。RBM47 可以直接结合并稳定长链非编码 RNA 小核仁 RNA 宿主基因 5（SNHG5），抑制 PTC 细胞增殖并在体外和体内激活自噬。SNHG5 通过招募泛素特异性肽酶 21（USP21）抑制 FOXO3 的泛素化和降解，从而促进 FOXO3 从细胞质向细胞核易位。我们的研究揭示了 RBM47/SNHG5/FOXO3 轴对 PTC 细胞增殖和自噬的调节机制，这可能为 PTC 的治疗提供有价值的见解。
