长链非编码 RNA HOTTIP 通过调节 miR-637 促进甲状腺乳头状癌细胞的增殖、侵袭和迁移。
LncRNA HOTTIP promotes papillary thyroid carcinoma cell proliferation, invasion and migration by regulating miR-637.
机构信息
Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; Key Discipline Laboratory of Clinical Medicine Henan, Zhengzhou 450052, Henan, China.
Pediatric Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
出版信息
Int J Biochem Cell Biol. 2018 May;98:1-9. doi: 10.1016/j.biocel.2018.02.013. Epub 2018 Feb 21.
BACKGROUND
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Besides, increasing evidence has demonstrated that long non-coding RNA (lncRNA) HOTTIP played a crucial role in cancer pathogenesis. MiR-637-mediated Akt1 was involved in cell growth, invasion and migration in various malignancies. This study was aimed to investigate the potential biological effect and regulatory mechanism of HOTTIP on cell proliferation, invasion and migration in PTC.
METHODS
Expression of HOTTIP, miR-637 and Akt1 were determined by quantitative RT-PCR (qRT-PCR) and western blotting in PTC tissues, normal tissues, PTC cells (TPC-1 and HTH83) or non-tumor thyroid cells (Nthy-ori 3-1). Cell proliferation, invasion and migration following HOTTIP knockdown were investigated in PTC cells. The target of HOTTIP was validated by RNA immunoprecipitation (RIP) and pull-down assay. Moreover, a xenograft model was performed.
RESULTS
HOTTIP was upregulated in human PTC tissues and PTC cell lines. In addition, HOTTIP knockdown inhibited the proliferation, invasion and migration in vitro together with in vivo tumorigenesis of PTC cells. Additionally, HOTTIP knockdown downregulated Akt1 expression and suppressed cell proliferation, invasion and migration in PTC cells by regulating miR-637. In contrast, miR-637 inhibitor reversed above-mentioned tendencies caused by HOTTIP knockdown.
CONCLUSION
HOTTIP is a potential oncogene in PTC and may serve as a therapeutic target for malignancies.
背景
甲状腺乳头状癌（PTC）是最常见的甲状腺恶性肿瘤。此外，越来越多的证据表明，长链非编码 RNA（lncRNA）HOTTIP 在癌症发病机制中发挥着关键作用。miR-637 介导的 Akt1 参与了多种恶性肿瘤中的细胞生长、侵袭和迁移。本研究旨在探讨 HOTTIP 对 PTC 细胞增殖、侵袭和迁移的潜在生物学作用和调控机制。
方法
通过定量 RT-PCR（qRT-PCR）和 Western blot 检测 PTC 组织、正常组织、PTC 细胞（TPC-1 和 HTH83）或非肿瘤甲状腺细胞（Nthy-ori 3-1）中 HOTTIP、miR-637 和 Akt1 的表达。在 PTC 细胞中研究 HOTTIP 敲低后细胞增殖、侵袭和迁移的变化。通过 RNA 免疫沉淀（RIP）和下拉实验验证 HOTTIP 的靶标。此外，还进行了异种移植模型实验。
结果
HOTTIP 在人 PTC 组织和 PTC 细胞系中上调。此外，HOTTIP 敲低抑制了 PTC 细胞的体外增殖、侵袭和迁移以及体内肿瘤发生。此外，HOTTIP 敲低通过调节 miR-637 下调 Akt1 表达并抑制 PTC 细胞的增殖、侵袭和迁移。相反，miR-637 抑制剂逆转了 HOTTIP 敲低引起的上述趋势。
结论
HOTTIP 是 PTC 的一种潜在癌基因，可作为恶性肿瘤的治疗靶点。
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