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长链非编码 RNA AGAP2-AS1 通过 miR-628-5p/KLF12 轴促进甲状腺乳头状癌的增殖和转移。

Long non-coding RNA AGAP2-AS1 promotes proliferation and metastasis in papillary thyroid cancer by miR-628-5p/KLF12 axis.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi 'an Jiaotong University, NO.277 of Yanta West Road, Shaanxi, 710061, Xi'an, China.

The Third Ward of Department of General Surgery, Rizhao People's Hospital, No.126 of Tai'an road, Shandong, 276800, Rizhao, China.

出版信息

J Bioenerg Biomembr. 2021 Apr;53(2):235-245. doi: 10.1007/s10863-021-09879-3. Epub 2021 Feb 18.

DOI:10.1007/s10863-021-09879-3
PMID:33604734
Abstract

Long non-coding RNA (lncRNA) AGAP2-AS1 acts as an oncogene in several types of cancers. However, the role and mechanism of AGAP2-AS1 in papillary thyroid carcinoma (PTC) remain unclear. Thus, in this study, we aimed to explore the role of AGAP2-AS1 in PTC. Our results showed that AGAP2-AS1 was significantly upregulated in PTC tissues. Knockdown of AGAP2-AS1 inhibited the proliferation, migration and invasion of PTC cells. In vivo experiment showed that AGAP2-AS1 knockdown inhibited the tumorigenesis of PTC. MiR-628-5p was found to act as a target miRNA of AGAP2-AS1 in PTC. The expression level of miR-628-5p in PTC tissues was negatively associated with that of AGAP2-AS1. Inhibition of miR-628-5p attenuated the effects of AGAP2-AS1 knockdown on PTC. Moreover, miR-628-5p directly bound to the 3'UTR of KLF12 and inhibited the expression of KLF12. Knockdown of KLF12 enhanced the inhibitory effects of miR-628-5p on PTC cell proliferation and metastasis. In conclusion, these findings indicated that AGAP2-AS1 exerted an oncogenic role in PTC progression and metastasis. The effects of AGAP2-AS1 might be mediated by the regulation of miR-628-5p/KLF12 axis.

摘要

长链非编码 RNA (lncRNA) AGAP2-AS1 在几种类型的癌症中充当癌基因。然而，AGAP2-AS1 在甲状腺乳头状癌 (PTC) 中的作用和机制尚不清楚。因此，在本研究中，我们旨在探讨 AGAP2-AS1 在 PTC 中的作用。我们的研究结果表明，AGAP2-AS1 在 PTC 组织中显著上调。AGAP2-AS1 的敲低抑制了 PTC 细胞的增殖、迁移和侵袭。体内实验表明，AGAP2-AS1 的敲低抑制了 PTC 的肿瘤发生。发现 miR-628-5p 是 PTC 中 AGAP2-AS1 的靶 miRNA。miR-628-5p 在 PTC 组织中的表达水平与 AGAP2-AS1 的表达水平呈负相关。抑制 miR-628-5p 减弱了 AGAP2-AS1 敲低对 PTC 的影响。此外，miR-628-5p 直接结合 KLF12 的 3'UTR 并抑制 KLF12 的表达。KLF12 的敲低增强了 miR-628-5p 对 PTC 细胞增殖和转移的抑制作用。总之，这些发现表明 AGAP2-AS1 在 PTC 的进展和转移中发挥致癌作用。AGAP2-AS1 的作用可能是通过调节 miR-628-5p/KLF12 轴介导的。

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