Sun Wei, Qin Yuan, Wang Zhihong, Dong Wenwu, He Liang, Zhang Ting, Zhang Hao
Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, China.
Front Oncol. 2021 Mar 2;11:610547. doi: 10.3389/fonc.2021.610547. eCollection 2021.
NEAT1 (nuclear paraspeckle assembly transcript 1) is an oncogenic long non-coding RNA (lncRNA) that facilitates tumorigenesis in multiple cancers. In papillary thyroid cancer (PTC), the molecular mechanism by which affects invasion and metastasis remains elusive. RNA sequencing was used to discover differentially expressed downstream genes. Protein and RNA expression analyses and immunohistochemistry detected the expression of , Transglutaminase 2 (TGM2), and microRNA-491 (miR-491) among PTC and non-cancerous tissues. Transwell and wound healing assays, and a mouse model of lung metastasis were used for further functional analyses. Bioinformatics was performed to predict miRNAs binding to both and . Rescue experiments and dual-luciferase reporter assays were performed. In PTC tissues, expression was markedly increased and regulated TGM2 expression. TGM2 was overexpressed in PTC, correlating positively with exthyroidal extension and lymph node metastasis. knockdown significantly inhibited invasion and metastasis. sponged miR-491, acting as a competing endogenous RNA to regulate expression. Fibronectin 1 (FN1) was predicted as a TGM2 target. TGM2 could transcriptionally activate FN1 by promoting nuclear factor kappa B (NFκb) p65 nuclear translocation, ultimately promoting PTC invasion/metastasis. These findings identify that sponges miR-491 to regulate TGM2 expression. TGM2 activates FN1 NFκb to promote PTC invasion and metastasis.
NEAT1（核旁斑组装转录本1）是一种致癌性长链非编码RNA（lncRNA），可促进多种癌症的肿瘤发生。在甲状腺乳头状癌（PTC）中，其影响侵袭和转移的分子机制仍不清楚。使用RNA测序来发现差异表达的下游基因。蛋白质和RNA表达分析以及免疫组织化学检测了PTC组织和非癌组织中NEAT1、转谷氨酰胺酶2（TGM2）和微小RNA-491（miR-491）的表达。采用Transwell和伤口愈合试验以及肺转移小鼠模型进行进一步的功能分析。进行生物信息学分析以预测与NEAT1和TGM2结合的微小RNA。进行了拯救实验和双荧光素酶报告基因检测。在PTC组织中，NEAT1表达明显增加并调节TGM2表达。TGM2在PTC中过表达，与甲状腺外扩展和淋巴结转移呈正相关。NEAT1敲低显著抑制侵袭和转移。NEAT1吸附miR-491，作为竞争性内源RNA调节TGM2表达。纤连蛋白1（FN1）被预测为TGM2的靶标。TGM2可通过促进核因子κB（NFκb）p65核转位转录激活FN1，最终促进PTC侵袭/转移。这些发现表明，NEAT1吸附miR-491以调节TGM2表达。TGM2通过NFκb激活FN1以促进PTC侵袭和转移。
