LncRNA FOXD2-AS1 Functions as a Competing Endogenous RNA to Regulate TERT Expression by Sponging miR-7-5p in Thyroid Cancer

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.

RETRACTED: Long Noncoding RNA FOXD2-AS1 Promotes the Malignancy of Cervical Cancer by Sponging MicroRNA-760 and Upregulating Hepatoma-Derived Growth Factor

“…The overall survival and progression-free survival of bladder cancer patients with high FOXD2-AS1 expression is shorter than that of bladder cancer patients with low FOXD2-AS1 expression (Su et al, 2018). Overexpressed FOXD2-AS1 is observed in multiple other types of human cancer, including hepatocellular carcinoma (Chang et al, 2018;Zhao et al, 2018;Xu et al, 2019), glioma (Ni et al, 2019), thyroid cancer Jiang et al, 2019;Liu et al, 2019), cutaneous melanoma (Ren et al, 2019), colorectal cancer (Zhu et al, 2018), esophageal squamous cell carcinoma (Bao et al, 2018), and non-small cell lung cancer (Rong et al, 2017). Nevertheless, FOXD2-AS1 expression status in cervical cancer has been unknown and warrants investigation.…”

“…A knockdown of FOXD2-AS1 inhibits papillary thyroid cancer cell proliferation, migration, invasion, the cancer stem cell-like phenotype, and anoikis resistance in vitro; promotes apoptosis; and hinders tumorigenesis in vivo Jiang et al, 2019;Liu et al, 2019). In hepatocellular carcinoma, silencing of FOXD2-AS1 expression suppresses cell proliferation, colony formation, metastasis, and epithelial-mesenchymal transition; induces cell cycle arrest at the G0-G1 transition; and decreases tumor growth and metastasis in vivo (Chang et al, 2018;Zhao et al, 2018;Xu et al, 2019).…”

“…FOXD2-AS1 is dysregulated in multiple types of human cancer, and its dysregulation is involved in the modulation of various tumor-associated biological processes (Rong et al, 2017;Bao et al, 2018;Chang et al, 2018;Su et al, 2018;Zhang et al, 2018;Zhao et al, 2018;Zhu et al, 2018;Jiang et al, 2019;Liu et al, 2019;Ni et al, 2019;Ren et al, 2019;Xu et al, 2019). To the best of our knowledge, however, the expression status and detailed roles of FOXD2-AS1 in cervical cancer are still unknown.…”

OTUD6B-AS1 Inhibits Viability, Migration, and Invasion of Thyroid Carcinoma by Targeting miR-183-5p and miR-21

“…Additionally, miRNA can be sponged by lncRNAs via competitive endogenous RNA (ceRNA) mechanism to regulate the abundance of miRNAs, then regulate miRNAs targets expression (14). In thyroid carcinoma, lncRNA FOXD2-AS1 promoted the tumorigenesis via sponging miR-7-5p to upregulate TERT expression (15). Currently, no OTUD6B-AS1 that act as ceRNAs have been reported in thyroid carcinomas.…”

<p>LncRNA FOXD2-AS1 Regulates miR-25-3p/Sema4c Axis To Promote The Invasion And Migration Of Colorectal Cancer Cells</p>

“…Through bioinformatics analysis, we predicted that miR-205 may target FOXD2-AS1, which has been characterized as an oncogenic long (>200 nt) non-coding RNA (lncRNA) in several types of cancers including CRC. 12,13 However, the roles of the interactions between FOXD2-AS1 and miR-205 in CRC remain unclear. This study aimed to investigate the interactions between FOXD2-AS1 and miR-205 in CRC.…”