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长链非编码 RNA HOXA-AS2 通过调节 miR-15a-5p/HOXA3 轴促进甲状腺乳头状癌的发生和进展。

LncRNA HOXA-AS2 Facilitates Tumorigenesis and Progression of Papillary Thyroid Cancer by Modulating the miR-15a-5p/HOXA3 Axis.

机构信息

1 Pharmacy Department, the First People's Hospital of Fuyang Hangzhou, Hangzhou, P.R. China.

2 General Surgery Department, Shaoxing Hospital of China Medical University, Shaoxing, P.R. China.

出版信息

Hum Gene Ther. 2019 May;30(5):618-631. doi: 10.1089/hum.2018.109. Epub 2019 Feb 26.

DOI:10.1089/hum.2018.109
PMID:30375256
Abstract

The long non-coding RNA HOXA-AS2 has been found to be an oncogene in several types of human malignant tumors. However, its role in regulating the occurrence and development of papillary thyroid cancer (PTC) is still unclear. The present study investigated the function and mechanism(s) of HOXA-AS2 in PTC progression. Using quantitative real-time polymerase chain reaction, HOXA-AS2 was found to be differentially expressed in PTC tissues and cell lines. Kaplan-Meier analysis indicated that the overall survival rate of patients with higher levels of HOXA-AS2 was lower than those with relatively lower levels. Loss-of-function assays revealed that knockdown inhibited PTC progression by inhibiting cellular proliferation, migration, and invasion and accelerating apoptosis. Mechanistically, loss-of-function assays showed a positive correlation between HOXA3 and HOXA-AS2 expression. Subcellular fractionation assay results revealed abundant HOXA-AS2 expression in the cytoplasm of PTC cells. Additionally, FOXD2-AS1 was found to upregulate HOXA3 expression by binding to miR-15a-5p. Finally, rescue assays demonstrated the overall function of the HOXA-AS2/miR-15a-5p/HOXA3 axis in PTC progression. These findings will significantly contribute to further research and the development of more efficient treatments for thyroid cancer in the future.

摘要

长链非编码 RNA HOXA-AS2 已被发现是几种人类恶性肿瘤的癌基因。然而,其在调节甲状腺乳头状癌(PTC)发生和发展中的作用尚不清楚。本研究探讨了 HOXA-AS2 在 PTC 进展中的功能和机制。通过实时定量聚合酶链反应,发现 HOXA-AS2 在 PTC 组织和细胞系中差异表达。Kaplan-Meier 分析表明,HOXA-AS2 水平较高的患者的总生存率低于 HOXA-AS2 水平相对较低的患者。功能丧失实验表明,下调抑制 PTC 进展,抑制细胞增殖、迁移和侵袭,并加速细胞凋亡。机制研究表明,HOXA3 和 HOXA-AS2 的表达呈正相关。亚细胞分馏实验结果表明,PTC 细胞的细胞质中存在丰富的 HOXA-AS2 表达。此外,FOXD2-AS1 通过与 miR-15a-5p 结合而上调 HOXA3 的表达。最后,挽救实验证明了 HOXA-AS2/miR-15a-5p/HOXA3 轴在 PTC 进展中的整体功能。这些发现将为未来进一步研究和开发更有效的甲状腺癌治疗方法做出重要贡献。

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