Abstract
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.
Highlights
Thyroid cancer is the most frequent endocrine malignancy with an increasing incidence [1, 2]
FOXD2-AS1 was found to be overexpressed in bladder cancer tissues, which further promoted bladder cancer progression and recurrence through forming a positive feedback loop with Akt and E2F1 [12]; in addition, Xu et al have reported that overexpression of FOXD2-AS1 contributed to carcinogenesis of gastric cancer, and predicted poor prognosis in gastric cancer patients [13]
We found that FOXD2-AS1 was upregulated in thyroid cancer tissues, and high levels of FOXD2AS1 were positively associated with poor recurrence-free survival in thyroid cancer patients via analyzing thyroid cancer RNA sequencing dataset from The Cancer Genome Atlas (TCGA)
Summary
Thyroid cancer is the most frequent endocrine malignancy with an increasing incidence [1, 2]. Accumulating studies have reported that lncRNAs play important role in the development, progression and metastasis of various types of cancer [8,9,10,11]. FOXD2-AS1 was found to be overexpressed in bladder cancer tissues, which further promoted bladder cancer progression and recurrence through forming a positive feedback loop with Akt and E2F1 [12]; in addition, Xu et al have reported that overexpression of FOXD2-AS1 contributed to carcinogenesis of gastric cancer, and predicted poor prognosis in gastric cancer patients [13]. Lu’s study has shown that FOXD-AS1 expression was significantly associated with overall survival in thyroid cancer patients [14]. To date, the functional role of FOXD2-AS1 in the progression of thyroid cancer is unclear
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