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长链非编码 RNA SNHG15 通过海绵吸附 miR-200a-3p 调控 YAP1-Hippo 信号通路在甲状腺乳头状癌中的作用。

LncRNA SNHG15 acts as a ceRNA to regulate YAP1-Hippo signaling pathway by sponging miR-200a-3p in papillary thyroid carcinoma.

机构信息

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, PR China.

College of Health Sciences, Jiangsu Normal University, Xuzhou, 221116, PR China.

出版信息

Cell Death Dis. 2018 Sep 20;9(10):947. doi: 10.1038/s41419-018-0975-1.

DOI:10.1038/s41419-018-0975-1
PMID:30237435
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6148237/
Abstract

Over the past decade, lncRNAs have been widely reported in human malignant tumors, including papillary thyroid carcinoma. LncRNA SNHG15 has been validated to be a tumor facilitator in several types of malignancies. The present study focused on the biological role of SNHG15 in papillary thyroid carcinoma. Based on the result of qPCR analysis, we identified the strong expression of SNHG15 in human papillary thyroid carcinoma tissues and cell lines. Moreover, Kaplan-Meier method was utilized to analyze the internal relevance between SNHG15 expression and overall survival rate of patients with papillary thyroid carcinoma. Loss-of-function assays were designed and conducted to determine the inhibitory effects of silenced SNHG15 on the cell growth and migration in papillary thyroid carcinoma. The mechanical investigation indicated that SNHG15 upregulated YAP1 by sponging miR-200a-3p. Moreover, results of gain-of-function assays validated the anti-oncogenic function of miR-200a-3p in papillary thyroid carcinoma. Finally, results of rescue assays validated the function of SNHG15-miR-200a-3p-YAP1 axis in papillary thyroid carcinoma. YAP1 is known as an oncogene and a core factor of Hippo pathway. Here, we demonstrated that SNHG15 inactivated Hippo signaling pathway in papillary thyroid carcinoma. In summary, our findings demonstrated that SNHG15 serves as a competitively endogenous RNA (ceRNA) to regulate YAP1-Hippo signaling pathway by sponging miR-200a-3p in papillary thyroid carcinoma.

摘要

在过去的十年中，lncRNAs 在人类恶性肿瘤中被广泛报道，包括甲状腺乳头状癌。lncRNA SNHG15 已被证实是几种恶性肿瘤的肿瘤促进因子。本研究专注于 SNHG15 在甲状腺乳头状癌中的生物学作用。基于 qPCR 分析的结果，我们确定了 SNHG15 在人甲状腺乳头状癌组织和细胞系中的强表达。此外，我们利用 Kaplan-Meier 方法分析了 SNHG15 表达与甲状腺乳头状癌患者总生存率之间的内在相关性。设计并进行了失活功能测定，以确定沉默 SNHG15 对甲状腺乳头状癌细胞生长和迁移的抑制作用。机械研究表明，SNHG15 通过海绵吸附 miR-200a-3p 而上调 YAP1。此外，功能获得测定的结果验证了 miR-200a-3p 在甲状腺乳头状癌中的抑癌作用。最后，挽救测定的结果验证了 SNHG15-miR-200a-3p-YAP1 轴在甲状腺乳头状癌中的功能。YAP1 是一种癌基因，也是 Hippo 通路的核心因子。在这里，我们证明了 SNHG15 在甲状腺乳头状癌中使 Hippo 信号通路失活。总之，我们的研究结果表明，SNHG15 通过海绵吸附 miR-200a-3p，作为竞争内源性 RNA（ceRNA）来调节 YAP1-Hippo 信号通路，从而在甲状腺乳头状癌中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/0b45a25e7666/41419_2018_975_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/6a8c8d513832/41419_2018_975_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/f261b6afa072/41419_2018_975_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/fd431dccf0ee/41419_2018_975_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/accc2b497425/41419_2018_975_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/1dfdc25f0268/41419_2018_975_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/98c5edb825ce/41419_2018_975_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/dddf6db816bb/41419_2018_975_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/0b45a25e7666/41419_2018_975_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/6a8c8d513832/41419_2018_975_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/f261b6afa072/41419_2018_975_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/fd431dccf0ee/41419_2018_975_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/accc2b497425/41419_2018_975_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/1dfdc25f0268/41419_2018_975_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/98c5edb825ce/41419_2018_975_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/dddf6db816bb/41419_2018_975_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b4/6148237/0b45a25e7666/41419_2018_975_Fig8_HTML.jpg

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