Huang Chan, Su Xuan, Zhou Da-Lei, Xu Bo-Heng, Liu Qing, Zhang Xiao, Tang Tao, Yang Xin-Hua, Ye Zu-Lu, He Cai-Yun
Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651#Dongfeng Road East, Guangzhou, Guangdong 510060, P.R. China.
Department of Head and Neck, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
Mol Ther Nucleic Acids. 2022 Mar 31;28:408-422. doi: 10.1016/j.omtn.2022.03.023. eCollection 2022 Jun 14.
Long non-coding RNAs (lncRNAs) act as important biological regulators in human cancers. The purpose of this study was to identify promising biomarkers for improved diagnosis and prognosis of papillary thyroid cancer (PTC). We analyzed the lncRNA expression profile of PTC patients and identified five upregulated and three downregulated lncRNAs as diagnostic biomarkers for PTC in our cohorts, which were confirmed using The Cancer Genome Atlas (TCGA) data. Several lncRNAs have been linked with lymph node (LN) metastasis in patients with PTC. A nomogram combining two lncRNAs, lnc-MPEG1-1:1 and lnc-ABCA12-5:2, with age, T stage, histological type, and predicted LN metastasis was developed. The area under the curve of the developed nomogram was 0.77 (0.73-0.81) in the TCGA training cohort and 0.88 (0.79-0.96) in our validation cohort. In particular, and experiments showed that overexpression of lnc-MPEG1-1:1 in PTC cell lines promoted the proliferation and migration of PTC. lnc-MPEG1-1:1 is overexpressed in the cytoplasm of PTC cells and functionally promotes cellular proliferation and migration and functions as a competitive endogenous RNA (ceRNA) by competitively occupying the shared binding sequences of miR-766-5p. lnc-MPEG1-1:1 knockdown suppressed epithelial-mesenchymal transition by miR-766-5p in PTC cells. Collectively, these results revealed a lnc-MPEG1-1:1/miR-766-5p pathway for thyroid cancer progression and suggest that a nomogram effectively predicted the LN metastasis in PTC.
长链非编码RNA(lncRNAs)在人类癌症中发挥着重要的生物学调节作用。本研究的目的是确定有前景的生物标志物,以改善甲状腺乳头状癌(PTC)的诊断和预后。我们分析了PTC患者的lncRNA表达谱,并确定了5个上调和3个下调的lncRNAs作为我们队列中PTC的诊断生物标志物,这一结果通过癌症基因组图谱(TCGA)数据得到了证实。一些lncRNAs与PTC患者的淋巴结(LN)转移有关。我们开发了一种列线图,将两个lncRNAs,即lnc-MPEG1-1:1和lnc-ABCA12-5:2,与年龄、T分期、组织学类型和预测的LN转移相结合。在TCGA训练队列中,所开发列线图的曲线下面积为0.77(0.73-0.81),在我们的验证队列中为0.88(0.79-0.96)。特别是, 和 实验表明,PTC细胞系中lnc-MPEG1-1:1的过表达促进了PTC的增殖和迁移。lnc-MPEG1-1:1在PTC细胞的细胞质中过表达,在功能上促进细胞增殖和迁移,并通过竞争性占据miR-766-5p的共享结合序列,作为一种竞争性内源RNA(ceRNA)发挥作用。lnc-MPEG1-1:1的敲低抑制了PTC细胞中miR-766-5p介导的上皮-间质转化。总的来说,这些结果揭示了一条用于甲状腺癌进展的lnc-MPEG1-1:1/miR-766-5p途径,并表明列线图能有效地预测PTC中的LN转移。