AUTHOR=Dou Xiaoqing , Zhou Qun , Wen Mingxiao , Xu Jiangyan , Zhu Yingping , Zhang Shuzhen , Xu Xianli 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.01700

DOI=10.3389/fphar.2019.01700

ISSN=1663-9812

ABSTRACT=<p>Although the functions of long noncoding RNA (lncRNA) called FOXD2 adjacent opposite strand RNA 1 (<italic>FOXD2-AS1</italic>) have been well studied in multiple human cancer types, its expression status and detailed roles in cervical cancer remain unknown and merit investigation. This study was aimed at assessing <italic>FOXD2-AS1</italic> expression in cervical cancer and at determining its effects on the aggressive behavior of cervical cancer <italic>in vitro</italic> and <italic>in vivo</italic>. Expression of <italic>FOXD2-AS1</italic> in cervical cancer tissues and cell lines was determined <italic>via</italic> reverse-transcription quantitative PCR. The effects of <italic>FOXD2-AS1</italic> on cervical cancer cells were examined by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow-cytometric analysis, migration and invasion assays, and an <italic>in vivo</italic> tumorigenicity assay. <italic>FOXD2-AS1</italic> was found to be significantly upregulated in cervical cancer tissues and cell lines. High <italic>FOXD2-AS1</italic> expression was notably linked with the Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and depth of cervical invasion in patients with cervical cancer. Kaplan–Meier survival analysis revealed significantly shorter overall survival of patients when the tumor expression of <italic>FOXD2-AS1</italic> was higher in comparison with those in patients with lower <italic>FOXD2-AS1</italic> expression. <italic>In vitro</italic> functional assays revealed that downregulation of <italic>FOXD2-AS1</italic> led to suppression of proliferation, migration, and invasiveness as well as to the induction of apoptosis of cervical cancer cells. In addition, <italic>FOXD2-AS1</italic> silencing hindered tumor growth <italic>in vivo</italic>. Mechanism investigation revealed that <italic>FOXD2-AS1</italic> functioned as a molecular sponge of microRNA-760 (miR-760). Furthermore, hepatoma-derived growth factor (<italic>HDGF</italic>) was validated as a direct target gene of miR-760 in cervical cancer cells. Moreover, an miR-760 knockdown reversed the effects of <italic>FOXD2-AS1</italic> silencing on cervical cancer cells. <italic>FOXD2-AS1</italic> possesses significant oncogenic activity in cervical cancer progression; this activity is mediated by sponging of miR-760 with consequent upregulation of HDGF. The <italic>FOXD2-AS1</italic>–miR-760–HDGF axis might harbor promising targets for novel treatment strategies of cervical cancer.</p>