Ge Ming-Hua, Jiang Lie-Hao, Wen Qing-Liang, Tan Zhuo, Chen Chao, Zheng Chuan-Ming, Zhu Xin, Chen Jia-Wen, Zhu Zi-Yu, Cai Xiu-Jun
Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
Department of Head and Neck Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310016, P.R. China.
Oncol Lett. 2018 Sep;16(3):3715-3725. doi: 10.3892/ol.2018.9080. Epub 2018 Jul 5.
The objective of the present study was to investigate the long non-coding RNA (lncRNA) and mRNA expression profiles that are associated with the invasion and metastasis of papillary thyroid carcinoma (PTC). Transwell invasion assays were used to screen three highly invasive sub-strains of the human PTC IHH4 cell line: IHH4-M1, IHH4-M2 and IHH4-M3. In addition, tumor-bearing nude mice were used to identify the invasive and metastatic capacity of the three sub-strains. Agilent lncRNA microarray chips were used to screen 795 differentially expressed lncRNAs and 788 differentially expressed mRNAs. A total of 10 lncRNAs and 10 mRNAs were randomly selected for RT-qPCR validation to confirm that the results were consistent with the microarray chips, suggesting that the results of the microarray chip analysis were relatively accurate. Gene ontology enrichment-based cluster analysis revealed that the differentially expressed genes were mainly associated with steroid biosynthesis, bioadhesion, intercellular adhesion and other metastasis-associated biological processes. The results of the pathway cluster analysis identified that the differentially expressed genes were associated with tumor metastasis-associated signaling pathways, including the cholesterol metabolic signaling pathway, the sterol regulatory element-binding protein signaling pathway and the integrin signaling pathway, suggesting that lncRNA may regulate PTC metastasis through various signaling pathways. The present study screened and constructed PTC metastasis-associated lncRNA and mRNA expression profiles, and it provides a molecular basis for the future study of high-risk molecular markers of PTC.
本研究的目的是调查与甲状腺乳头状癌（PTC）侵袭和转移相关的长链非编码RNA（lncRNA）和mRNA表达谱。采用Transwell侵袭实验筛选出人PTC IHH4细胞系的三个高侵袭性亚株：IHH4-M1、IHH4-M2和IHH4-M3。此外，利用荷瘤裸鼠鉴定这三个亚株的侵袭和转移能力。使用安捷伦lncRNA微阵列芯片筛选出795个差异表达的lncRNA和788个差异表达的mRNA。随机选择10个lncRNA和10个mRNA进行RT-qPCR验证，以确认结果与微阵列芯片一致，表明微阵列芯片分析结果相对准确。基于基因本体富集的聚类分析显示，差异表达基因主要与类固醇生物合成、生物黏附、细胞间黏附等转移相关的生物学过程有关。通路聚类分析结果确定，差异表达基因与肿瘤转移相关信号通路有关，包括胆固醇代谢信号通路、固醇调节元件结合蛋白信号通路和整合素信号通路，提示lncRNA可能通过多种信号通路调控PTC转移。本研究筛选并构建了PTC转移相关的lncRNA和mRNA表达谱，为未来研究PTC高危分子标志物提供了分子基础。
