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

Abstract

Although the functions of long noncoding RNA (lncRNA) called FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) 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 FOXD2-AS1 expression in cervical cancer and at determining its effects on the aggressive behavior of cervical cancer in vitro and in vivo. Expression of FOXD2-AS1 in cervical cancer tissues and cell lines was determined via reverse-transcription quantitative PCR. The effects of FOXD2-AS1 on cervical cancer cells were examined by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-Htetrazolium bromide (MTT) assay, flow-cytometric analysis, migration and invasion assays, and an in vivo tumorigenicity assay. FOXD2-AS1 was found to be significantly upregulated in cervical cancer tissues and cell lines. High FOXD2-AS1 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 FOXD2-AS1 was higher in comparison with those in patients with lower FOXD2-AS1 expression. In vitro functional assays revealed that downregulation of FOXD2-AS1 led to suppression of proliferation, migration, and invasiveness as well as to the induction of apoptosis of cervical cancer cells. In addition, FOXD2-AS1 silencing hindered tumor growth in vivo. Mechanism investigation revealed that FOXD2-AS1 functioned as a molecular sponge of microRNA-760 (miR-760). Furthermore, hepatoma-derived growth factor (HDGF) was validated as a direct target gene of miR-760 in cervical cancer cells. Moreover, an miR-760 knockdown reversed the effects of FOXD2-AS1 silencing on cervical cancer cells. FOXD2-AS1 possesses significant oncogenic activity in cervical cancer progression; this activity is mediated by sponging

Hepatoma-Derived Growth Factor: An Overview and Its Role as a Potential Therapeutic Target Molecule for Digestive Malignancies

“…The fact that HDGF is a representative member of a gene family ( Figure 1; Figure 2) might be advantageous when we consider it as a therapeutic target. Recently, the significant roles of HDGF in malignant diseases were reported for many non-digestive malignant diseases, including osteosarcoma [61,62], endometrial cancer [63,64], lung cancer [65][66][67], malignant glioma [68][69][70], cervical cancer [71], ovarian cancer [72] and breast cancer [73]. Thus, HDGF is considered as a potential target molecule for anticancer therapy.…”

“…Recently, non-coding RNAs, such as microRNAs and long non-coding RNAs (lncRNAs), which modulate the function of the target genes, have been shown to have an important role in several diseases [77,78]. Indeed, various microRNAs [40,61,62,[64][65][66][67]69,72] and lncRNAs [49,61,69,71,73] have been suggested to be involved in the regulation of the functions of HDGF, findings that may support the development of HDGF-targeting therapies. For instance, lncRNA HLA complex P5 (lnc HCP5) was reported to cause gemcitabine resistance in pancreatic cancer cells, through the upregulation of miR-214-3p and its target gene, HDGF [40].…”

<p>Long Non-Coding RNA LINC00511 Accelerates Proliferation and Invasion in Cervical Cancer Through Targeting miR-324-5p/DRAM1 Axis</p>

“…3 It is reported that the 5-year survival rate of patients with advanced cervical cancer is less than 40%, mainly due to tumor metastasis and recurrence. 4,5 Human papillomavirus (HPV) infection is the main pathogenic factor of cervical cancer and the main content of early diagnosis, but nearly 15% of patients are HPV-negative. 6,7 Therefore, further study is required to reveal the molecular mechanism of the occurrence and development of cervical cancer and identify novel therapeutic targets of HPV-positive and HPV-negative cervical cancer.…”

The role of FOXD2-AS1 in cancer: a comprehensive study based on data mining and published articles

“…Moreover, in glioma, Dong et al [ 36 ] found that FOXD2-AS1 can act as an endogenous sponge of miR-185, which can bind AKT1 to promote cell proliferation and metastasis. In other cancers, FOXD2-AS1 has been suggested to contribute to migration and invasion of tumors by sponging miR-185-5p [ 15 , 28–30 , 36 , 38 , 40 , 46 ], miR-25-3p [ 20 ], miR-98-5p [ 47 ], miR-31 [ 48 ], miR-7-5p [ 49 ], miR-760 [ 44 ], miR-195 [ 24 ], miR-145-5p [ 25 ], miR-363-5p [ 13 , 17 ], miR-143 [ 50 ], miR-485-5p [ 37 ], and miR-206 [ 14 ]. Recent work has shown that lncRNAs influence the occurrence and development of tumors by regulating gene expression at the transcriptional or post-transcriptional level.…”