Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, ErDao District, Changchun 13033, China.
Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, 126 XiantaiStreet, ErDao District, Changchun 13033, China.
Biomed Pharmacother. 2019 Oct;118:109298. doi: 10.1016/j.biopha.2019.109298. Epub 2019 Aug 9.
The long noncoding RNA myocardial infarction associated transcript (MIAT) was reported to be involved in the progression of multiple cancers. However, the exact roles and molecular mechanisms of MIAT in papillary thyroid cancer (PTC) progression are still unknown. We examined the expression levels of lncRNA MIAT in 50 paired PTC tissue specimens and four PTC cell lines by real time quantitative PCR (qRT-PCR). Cell counting kit 8, colony formation, wound healing and transwell assays were performed to examine the effect of MIAT on proliferation, colony formation, migration and invasion. Tumor xenograft models were created to detect the role of MIAT in vivo tumorigenesis. The target relationships were predicted by miRcode algorithm, and confirmed by dual luciferase reporter gene assay and qRT-PCR. We found that MIAT was up-regulated in PTC tissues and cell lines. High MIAT expression was positively associated with advanced tumor-node-metastasis (TNM) stage and lymph node metastasis. Functional assays showed that knockdown of MIAT in PTC cells significantly inhibited cell proliferation, colony formation, migration and invasion in vitro, as well as impaired tumor growth in vivo. Luciferase assays further confirmed that miR-212 interacts with MIAT. Additionally, the negatively correlation of miR-212 with MIAT was verified in patients' samples. Repression of miR-212 partly abrogated the inhibitory effects of MIAT knockdown on PTC cells. Taken together, these results indicated that MIAT might be an oncogenic lncRNA that promoted PTC progression, and might be a potential therapeutic target for PTC.
长链非编码 RNA 心肌梗死相关转录物（MIAT）被报道参与多种癌症的进展。然而，MIAT 在甲状腺乳头状癌（PTC）进展中的确切作用和分子机制尚不清楚。我们通过实时定量 PCR（qRT-PCR）检测了 50 对 PTC 组织标本和 4 种 PTC 细胞系中 lncRNA MIAT 的表达水平。细胞计数试剂盒 8、集落形成、划痕愈合和 Transwell 测定用于检测 MIAT 对增殖、集落形成、迁移和侵袭的影响。创建肿瘤异种移植模型以检测 MIAT 在体内肿瘤发生中的作用。miRcode 算法预测靶关系，并通过双荧光素酶报告基因检测和 qRT-PCR 进行验证。我们发现 MIAT 在 PTC 组织和细胞系中上调。高 MIAT 表达与晚期肿瘤-淋巴结-转移（TNM）分期和淋巴结转移呈正相关。功能测定表明，PTC 细胞中 MIAT 的敲低显著抑制了体外细胞增殖、集落形成、迁移和侵袭，以及体内肿瘤生长。荧光素酶测定进一步证实 miR-212 与 MIAT 相互作用。此外，在患者样本中验证了 miR-212 与 MIAT 的负相关。miR-212 的抑制部分消除了 MIAT 敲低对 PTC 细胞的抑制作用。综上所述，这些结果表明 MIAT 可能是一种促进 PTC 进展的致癌 lncRNA，可能是 PTC 的潜在治疗靶点。
