LncRNA FOXD2-AS1 Functions as a Competing Endogenous RNA to Regulate TERT Expression by Sponging miR-7-5p in Thyroid Cancer
LncRNA FOXD2-AS1 Functions as a Competing Endogenous RNA to Regulate TERT Expression by Sponging miR-7-5p in Thyroid Cancer
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LncRNA FOXD2-AS1 作为竞争性内源 RNA 通过海绵 miR-7-5p 在甲状腺癌中调节 TERT 表达
DOI：
10.3389/fendo.2019.00207
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发表时间：
2019-04-08
影响因子：
5.2
通讯作者：
Sun, Hui
中科院分区：
文献类型：
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作者：
Liu, Xiaoli;Fu, Qingfeng;Sun, Hui
长链非编码RNA FOXD2相邻反义链RNA 1（FOXD2 - AS1）已被广泛报道与多种癌症的进展和复发有关。然而，FOXD2 - AS1在甲状腺癌中的临床意义和功能作用仍不明确。通过分析来自癌症基因组图谱（TCGA）的甲状腺癌RNA测序数据集，对FOXD2 - AS1的表达进行评估。开展体外和体内实验，以评估FOXD2 - AS1在甲状腺癌细胞中的生物学作用。采用蛋白质免疫印迹法、荧光素酶报告基因实验、免疫沉淀（IP）及RNA免疫沉淀（RIP）实验，来确定介导FOXD2 - AS1在甲状腺癌细胞中生物学作用的潜在微小RNA（miRNA）和信使核糖核酸（mRNA）靶点。
FOXD2 - AS1在甲状腺癌组织和细胞中表达上调。FOXD2 - AS1的高表达与甲状腺癌的临床分期、复发显著相关。沉默FOXD2 - AS1可在体外抑制甲状腺癌细胞的癌干细胞样表型，并减弱其对失巢凋亡的抗性。下调FOXD2 - AS1在体内可抑制甲状腺癌细胞的成瘤能力。FOXD2 - AS1作为miR - 7 - 5p的竞争性内源性RNA（ceRNA），上调端粒酶逆转录酶（TERT）的表达，进而促进甲状腺癌细胞的癌干细胞特性及对失巢凋亡的抗性。我们的研究结果表明，FOXD2 - AS1在甲状腺癌的发生发展中发挥癌基因调控作用，促使甲状腺癌早期复发。
Long non-coding RNA FOXD2 Adjacent Opposite Strand RNA 1 (FOXD2-AS1) has been widely reported to be implicated in the progression and recurrence of several cancers. The clinical significance and functional role of FOXD2-AS1 in thyroid carcinoma remain unknown. FOXD2-AS1 expression was evaluated by analyzing thyroid cancer RNA sequencing dataset from The Cancer Genome Atlas (TCGA). In vitro and in vivo assays were performed to assess the biological roles of FOXD2-AS1 in thyroid cancer cells. Western blot, luciferase, immunoprecipitation (IP), and RNA immunoprecipitation (RIP) assays were used to identify the underlying miRNA and mRNA target mediating the biological roles of FOXD2-AS1 in thyroid cancer cells. FOXD2-AS1 was upregulated in thyroid carcinoma tissues and cells. High expression of FOXD2-AS1 significantly correlated with clinical stage, recurrence of thyroid carcinoma. Silencing FOXD2-AS1 inhibited cancer stem cell-like phenotypes and attenuates the anoikis resistance in vitro. Downregulating FOXD2-AS1 represses the tumorigenesis of thyroid carcinoma cells in vivo. FOXD2-AS1 acts as a competitive endogenous RNA (ceRNA) for miR-7-5p, up-regulating the expression of telomerase reverse transcriptase (TERT), which further promotes the cancer stem cells features and anoikis resistance in thyroid cancer cells. Our findings indicate that FOXD2-AS1 functions as an oncogenic regulator in the development of thyroid cancer, contributing to early recurrence of thyroid cancer.