Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR, China.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, PR, China.
Curr Med Chem. 2024;31(24):3818-3833. doi: 10.2174/0929867330666230522115945.
Thyroid cancer (TC), the most common endocrine malignant tumor, is increasingly causing a huge threat to our health nowadays.
To explore the tumorigenesis mechanism of thyroid cancer, we identified that long intergenic non-coding RNA-00891 (LINC00891) was upregulated in TC using the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and local databases. LINC00891 expression was correlated with histological type and lymph node metastasis (LNM). The high expression of LINC00891 could serve as a diagnostic marker for TC and its LNM. experiments demonstrated that LINC00891 knockdown could inhibit cell proliferation, migration, invasion and prompt apoptosis and G1 arrest of TC cells. We also investigated the related mechanisms of LINC00891 promoting TC progression using RNA sequencing, Gene Set Enrichment Analysis, and Western blotting.
Our experiments demonstrated that LINC00891 promoted TC progression via the EZH2-SMAD2/3 signaling axis. In addition, overexpression of EZH2 could reverse the suppressive epithelial-to-mesenchymal transition (EMT) caused by LINC00891 knockdown.
In conclusion, the LINC00891/EZH2/SMAD2/3 regulatory axis participated in tumorigenesis and metastasis of thyroid cancer, which may provide a novel target for treatment.
甲状腺癌（TC）是最常见的内分泌恶性肿瘤，目前它对我们健康的威胁日益增大。
为了探究甲状腺癌的发生机制，我们通过癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和本地数据库发现长链非编码 RNA-00891（LINC00891）在 TC 中呈上调表达。LINC00891 的表达与组织学类型和淋巴结转移（LNM）相关。LINC00891 的高表达可作为 TC 及其 LNM 的诊断标志物。实验表明，LINC00891 敲低可抑制 TC 细胞的增殖、迁移、侵袭，并促使其发生凋亡和 G1 期阻滞。我们还通过 RNA 测序、基因集富集分析和 Western blot 研究了 LINC00891 促进 TC 进展的相关机制。
我们的实验表明，LINC00891 通过 EZH2-SMAD2/3 信号轴促进 TC 进展。此外，过表达 EZH2 可逆转 LINC00891 敲低引起的抑制性上皮间质转化（EMT）。
总之，LINC00891/EZH2/SMAD2/3 调控轴参与了甲状腺癌的发生和转移，可能为治疗提供新的靶点。
