长链非编码 RNA FAM230B 通过海绵吸附 miR-378a-3p/WNT5A 轴促进甲状腺乳头状癌的转移。
LncRNA FAM230B promotes the metastasis of papillary thyroid cancer by sponging the miR-378a-3p/WNT5A axis.
机构信息
Department of Otolaryngology Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China; Department of Head and Neck Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China; Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, 200233, China; Otolaryngological institute, Shanghai Jiao Tong University, Shanghai, 200233, China.
Department of Otolaryngology Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China; Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, 200233, China; Otolaryngological institute, Shanghai Jiao Tong University, Shanghai, 200233, China.
出版信息
Biochem Biophys Res Commun. 2021 Mar 26;546:83-89. doi: 10.1016/j.bbrc.2021.01.109. Epub 2021 Feb 9.
Emerging evidence indicates that the dysregulation of long non-coding RNAs (lncRNAs) plays critical roles in the progression of papillary thyroid cancer (PTC). In this study, we found consistently elevated expression levels of the lncRNA FAM230B in PTC tissues, both in newly generated RNA-seq data and in datasets from the GEO and TCGA databases. We demonstrated that the expression of FAM230B can be used for the diagnosis of PTC and is also strongly associated with lymph node metastasis. The potential biological functions of FAM230B and molecular mechanisms by which it regulates PTC progression were investigated. Functionally, FAM230B promoted the migration and invasion of PTC cells in vitro and in vivo. Mechanistically, FAM230B sponged miR-378a-3p and showed competitive binding to the 3'-UTR of WNT5A. FAM230B overexpression resulted in elevated WNT5A expression and thereby regulated the epithelial-mesenchymal transition in PTC cells. Finally, we verified that both miR-378a-3p overexpression and WNT5A silencing effectively offset the impacts of FAM230B on PTC cell migration and invasion. In conclusion, our study demonstrated the oncogenic function of the lncRNA FAM230B in PTC cells, providing a novel target for PTC diagnosis and therapy.
越来越多的证据表明，长非编码 RNA（lncRNA）的失调在甲状腺乳头状癌（PTC）的进展中起着关键作用。在这项研究中，我们在 PTC 组织中发现了 lncRNA FAM230B 的表达水平始终升高，无论是在新生成的 RNA-seq 数据中，还是在 GEO 和 TCGA 数据库的数据集。我们证明 FAM230B 的表达可用于 PTC 的诊断，并且与淋巴结转移密切相关。研究了 FAM230B 的潜在生物学功能及其调节 PTC 进展的分子机制。功能上，FAM230B 促进了 PTC 细胞在体外和体内的迁移和侵袭。机制上，FAM230B 吸附 miR-378a-3p 并与 WNT5A 的 3'-UTR 显示竞争性结合。FAM230B 的过表达导致 WNT5A 表达升高，从而调节 PTC 细胞的上皮-间充质转化。最后，我们验证了 miR-378a-3p 过表达和 WNT5A 沉默均可有效抵消 FAM230B 对 PTC 细胞迁移和侵袭的影响。总之，我们的研究证明了 lncRNA FAM230B 在 PTC 细胞中的致癌功能，为 PTC 的诊断和治疗提供了一个新的靶点。
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