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长链非编码 RNA ABHD11-AS1 通过 miR-199a-5p/SLC1A5 轴作为竞争性内源性 RNA 调节甲状腺乳头状癌的进展。

Long noncoding RNA ABHD11-AS1 functions as a competing endogenous RNA to regulate papillary thyroid cancer progression by miR-199a-5p/SLC1A5 axis.

机构信息

Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, PR China.

出版信息

Cell Death Dis. 2019 Aug 14;10(8):620. doi: 10.1038/s41419-019-1850-4.

Abstract

With the increasing incidence of papillary thyroid cancer (PTC), more attention has been paid to exploring the mechanism of PTC initiation and progression. In addition, ectopic expression of long noncoding RNAs (lncRNAs) is reported to play a pivotal role in multiple human cancers. Based on these findings, we examined lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) expression and its clinical significance, biological function and mechanism in PTC. First, we analyzed thyroid ABHD11-AS1 expression in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Then, qRT-PCR was applied to detect the expression in paired PTC tissues and adjacent normal tissues, as well as in PTC cell lines (TPC-1 and K-1) and a normal thyroid follicular epithelium cell line (Nthy-ori3-1). In addition, we validated the relationship between ABHD11-AS1 expression and clinicopathological features by the Pearson X test. The oncogenic role of ABHD11-AS1 and its regulation of miR-199a-5p in PTC were examined by biological assays. Finally, bioinformatics analysis and mechanism assays were used to elucidate the underlying mechanism. We found that ABHD11-AS1 was remarkably overexpressed in PTC, and high expression was related to tumor size, lymph node metastasis, extrathyroidal extension and advanced TNM stage. Moreover, ABHD11-AS1 enhanced the abilities of cell proliferation, migration, and invasion, inhibited apoptosis in vitro, promoted tumorigenesis in vivo via sponging miR-199a-5p and then induced SLC1A5 activation. In addition, rescue assays were performed to confirm the ABHD11-AS1/miR-199a-5p/SLC1A5 axis. Taken together, the data show that ABHD11-AS1 acts as a competing endogenous RNA (ceRNA) to exert malignant properties in PTC through the miR-199a-5p/SLC1A5 axis. Therefore, our study may shed light on PTC diagnosis and therapies.

摘要

随着甲状腺乳头状癌 (PTC) 的发病率不断增加,人们越来越关注探索 PTC 发生和发展的机制。此外,长链非编码 RNA (lncRNA) 的异位表达被报道在多种人类癌症中发挥关键作用。基于这些发现,我们研究了 lncRNA ABHD11 反义 RNA 1 (ABHD11-AS1) 在 PTC 中的表达及其临床意义、生物学功能和机制。首先,我们分析了癌症基因组图谱 (TCGA) 和基因表达综合数据库 (GEO) 中的甲状腺 ABHD11-AS1 表达。然后,应用 qRT-PCR 检测配对的 PTC 组织和相邻正常组织、PTC 细胞系 (TPC-1 和 K-1) 和正常甲状腺滤泡上皮细胞系 (Nthy-ori3-1) 中的表达。此外,我们通过 Pearson X 检验验证了 ABHD11-AS1 表达与临床病理特征的关系。通过生物测定研究了 ABHD11-AS1 的致癌作用及其对 PTC 中 miR-199a-5p 的调控作用。最后,通过生物信息学分析和机制测定阐明了潜在的机制。我们发现 ABHD11-AS1 在 PTC 中显著过表达,高表达与肿瘤大小、淋巴结转移、甲状腺外侵犯和晚期 TNM 分期有关。此外,ABHD11-AS1 在体外增强了细胞增殖、迁移和侵袭能力,抑制了细胞凋亡,通过海绵吸附 miR-199a-5p 并进而诱导 SLC1A5 激活,促进体内肿瘤发生。此外,还进行了挽救实验以证实 ABHD11-AS1/miR-199a-5p/SLC1A5 轴。总之,数据表明 ABHD11-AS1 通过 miR-199a-5p/SLC1A5 轴作为竞争内源性 RNA (ceRNA) 在 PTC 中发挥恶性作用。因此,我们的研究可能为 PTC 的诊断和治疗提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/952a/6692390/43b5d1ea0e6d/41419_2019_1850_Fig1_HTML.jpg

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