FOXD2 Adjacent Opposite Strand RNA 1 Research Articles

FOXD2-AS1 inhibits the proliferation and migration in prostate cancer: an in vitro and in vivo study

FOXD2 Adjacent Opposite Strand RNA 1 (FOXD2-AS1), a long noncoding RNA (lncRNA), exhibits specifically elevated in numerous cancerous cells. Numerous studies have shown that FOXD2-AS1 encourages cellular proliferation, migration and invasion. Nevertheless, the exact mechanism through which FOXD2-AS1 contributes to prostate cancer (PCa) remains unclear. Consequently, we aimed to explore the implications of FOXD2-AS1 on the growth of PCa. Initially, an elevation of FOXD2-AS1 observed in PCa cells (PC-3, DU145 and Lncap) than the prostate normal cell line RWPE2. Then, PC-3 cells were tranafected with shFOXD2-AS1, sh-Numerical Control (shNC) or FOXD2-AS1 to assess the implications of FOXD2-AS. Cell growth was measured with cell counting kit-8 (CCK8) and 5-ethynyl-2′-deoxyuridine (EDU) assays, and cell invasion and migration were assessed by Transwell assays, which demonstrated that FOXD2-AS1 silence impeded proliferation, migration and invasion of PC-3 cells. Additionally, we discovered that FOXD2-AS1 bonded with miR-206/programmed cell death protein 10 (PDCD10) trough analyzing the interaction sites of lncRNA, miRNA and protein. Then, these interaction abilities were confirmed by dual-luciferase reporter assays and RT-qPCR, suggesting FOXD2-AS1 could upregulate the amount of PDCD10 through suppressing miR-206. Furthermore, the role of FOXD2-AS1 silencing on PCa carcinogenesis were assessed. In vivo experiment, shFOXD2-AS1 led to a notable reduction in both the size and weight of PCa. These findings indicated that FOXD2-AS1 silencing effectively hindered the progression of prostate cancer. In conclusion, the upregulation of FOXD2-AS1 was observed in PCa, and the knockdown of FOXD2-AS1 could alleviated tumor development by targeting miR-206 to upregulate PDCD10 expression.

Overexpression of FOXD2-AS1 enhances proliferation and impairs differentiation of glioma stem cells by activating the NOTCH pathway via TAF-1.

Emerging data have highlighted the importance of long noncoding RNAs (lncRNAs) in exerting critical biological functions and roles in different forms of brain cancer, including gliomas. In this study, we sought to investigate the role of lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2‐AS1) in glioma cells. First, we used sphere formation assay and flow cytometry to select U251 glioma stem cells (GSCs). Then, we quantified the expression of lncRNA FOXD2‐AS1, TATA‐box binding protein associated factor 1 (TAF‐1) and NOTCH1 in glioma tissues and GSCs, as well as the expression of GSC stem markers, OCT4, SOX2, Nanog, Nestin and CD133 in GSCs. Colony formation assay, sphere formation assay, and flow cytometry were used to evaluate GSC stemness. Next, the correlations among lncRNA FOXD2‐AS1, TAF‐1 and NOTCH1 were investigated. LncRNA FOXD2‐AS1, TAF‐1 and NOTCH1 were found to be elevated in glioma tissues and GSCs, and silencing lncRNA FOXD2‐AS1 inhibited stemness and proliferation, while promoting apoptosis and differentiation of GSCs. LncRNA FOXD2‐AS1 overexpression also led to increased NOTCH1 by recruiting TAF‐1 to the NOTCH1 promoter region, thereby promoting stemness and proliferation, while impairing cell apoptosis and differentiation. Mechanistically, lncRNA FOXD2‐AS1 elevation promoted glioma in vivo by activating the NOTCH signalling pathway via TAF‐1 upregulation. Taken together, the key findings of our investigation support the proposition that downregulation of lncRNA FOXD2‐AS1 presents a viable and novel molecular candidate for improving glioma treatment.

Downregulation of lncRNA FOXD2-AS1 Confers Radiosensitivity to Gastric Cancer Cells via miR-1913/SETD1A Axis

Long noncoding RNA FOXD2 adjacent opposite strand RNA1 (FOXD2-AS1) plays an oncogenic role in various cancers, including gastric cancer (GC). However, the function of FOXD2-AS1 in regulating radiosensitivity of GC cells and its underlying molecular mechanisms have not been elucidated. This study aimed to figure out the potential mechanisms of FOXD2-AS1 in regulating GC cell radiosensitivity. RT-qPCR revealed upregulation of FOXD2-AS1 in GC cells exposed to radiation. Subcellular fractionation assay was used to localize FOXD2-AS1 in GC cells. Colony formation, MTT, EdU, and flow cytometry assays were performed to investigate the role of FOXD2-AS1 in regulating cell proliferation, cell cycle progression, and cell apoptosis. Western blotting was used to assess protein levels of apoptosis-associated markers and SET domain containing 1A (SETD1A). Homologous recombination reporter assay was conducted to explore the effect of FOXD2-AS1 on DNA damage repair. The downstream molecules of FOXD2-AS1 were identified with RNA pulldown, luciferase reporter, and RNA immunoprecipitation assays. The results showed that FOXD2-AS1 knockdown suppressed cell proliferation and cell cycle progression and promoted cell apoptosis and radiosensitivity of GC. FOXD2-AS1 could bind with miR-1913 in GC cells. In addition, miR-1913 targeted SETD1A, which was highly expressed in GC cells. Overexpression of SETD1A reversed FOXD2-AS1 silencing-induced effects on proliferation, apoptosis, and radiosensitivity of GC cells. In conclusion, knocking down FOXD2-AS1 enhances the radiosensitivity of GC cells by sponging miR-1913 to upregulate SETD1A expression.

MiR‑4306 inhibits the malignant behaviors of colorectal cancer by regulating lncRNA FoxD2‑AS1.

MicroRNA (miR)-4306 and FoxD2-adjacent opposite strand RNA 1 (FOXD2-AS1) are cancer-related genes involved in tumor progression. However, the potential functional roles of miR-4306 and FoxD2-AS1 in colorectal cancer (CRC) development remain unknown. The present study aimed to investigate the biological functions and the molecular mechanisms of miR-4306 and FoxD2-AS1 in CRC. Reverse transcription-quantitative PCR analysis was performed to determine the expression levels of FoxD2-AS1 and miR-4306 in CRC tissues and cell lines. Functional experiments, including Cell Counting Kit-8, colony formation, cell cycle assays and western blotting, were conducted to examine the effects of FoxD2-AS1 and miR-4306 on the malignant behaviors of CRC cells. In addition, the relationship between FoxD2-AS1 and miR-4306 was assessed using a dual-luciferase reporter assay and Pearson's correlation analysis. Compared with normal samples and cells, FoxD2-AS1 expression was increased and miR-4306 expression was decreased in CRC tissues and cells. Functional experiments demonstrated that silencing FoxD2-AS1 inhibited proliferation and induced cell arrest at G0/G1 phase in CRC cells, while the overexpression of FoxD2-AS1 showed opposite results. Ki-67 and proliferating cell nuclear antigen expression levels were decreased after transfection with small interfering RNA FoxD2-AS1, but were increased after transfection with FoxD2-AS1 overexpression plasmid. Furthermore, investigations into the underling mechanism revealed that FoxD2-AS1 functioned as a molecular sponge of miR-4306. The inhibitory effects of FoxD2-AS1 silencing on CRC progression were reversed by miR-4306 knockdown. Collectively, the present study demonstrated that FoxD2-AS1 functioned as an oncogene in CRC progression, and that miR-4306 could inhibit the malignant behaviors of CRC by regulating FoxD2-AS1. Thus, the current study provided a promising therapeutic target for CRC treatment.

M6A methyltransferase METTL3-mediated lncRNA FOXD2-AS1 promotes the tumorigenesis of cervical cancer

Recent studies have indicated that long noncoding RNA (lncRNA) and N6-methyladenosine (m6A) methylation modification play critical roles in human cancers; however, their regulation on cervical cancer is largely unclear. Here, our study tries to investigate the underlying mechanisms by which lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) modulates cervical cancer tumorigenesis. Results illuminated that FOXD2-AS1 expression was significantly upregulated in cervical cancer cells and tissue, which was closely correlated to the unfavorable prognosis. Functionally, gain and loss-of-function assays showed that FOXD2-AS1 promoted the migration and proliferation of cervical cancer cells. Besides, FOXD2-AS1 silencing repressed the tumor growth in vivo. Mechanistically, m6A methyltransferase methyltransferase-like 3 (METTL3) enhanced the stability of FOXD2-AS1 and maintained its expression. Moreover, FOXD2-AS1 recruited lysine-specific demethylase 1 (LSD1) to the promoter region of p21 to silence its transcription abundance. In conclusion, these findings support that METTL3/FOXD2-AS1 accelerates cervical cancer progression via a m6A-dependent modality, which may serve as a potential therapeutic target for cervical cancer.

Long Non-coding RNA FOXD2-AS1 Promotes Proliferation, Migration, and Invasion in Cholangiocarcinoma Through Regulating miR-760/E2F3 Axis.

Long non-coding RNA (lncRNA) has been testified to influence the initiation and evolution of sundry carcinomas. Recently, lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) has been found to display vital regulating functions in various cancers. qRT-PCR was used to verify the dysregulation of FOXD2-AS1 expression in CCA cells and tissues, and the correlation of FOXD2-AS1 expression with clinicopathological characteristics was investigated. The viability, migration, and invasion of CCA cells were verified through CCK-8 assay, colony formation experiment, wound healing assay, and transwell assay. The regulatory networks of FOXD2-AS1 were analyzed by Bioinformatic prediction and dual-luciferase reporter assay. We discovered that FOXD2-AS1 was significantly upregulated in CCA and its up-regulation was closely correlated with terminal TNM stage, lymph node metastasis and poor survival in the current research. In addition, it was revealed that FOXD2-AS1 was an independent prognostic factor. Functional tests uncovered that the cell viability, migration, and invasion could be restrained through downregulating the expression of FOXD2-AS1, while FOXD2-AS1 overexpression could facilitate the cell viability, migration, and invasion. Mechanistically, FOXD2-AS1 was founded to interact directly with miR-760 and the oncogene E2F3 was the downstream target of miR-760 through bioinformatic prediction and dual-luciferase reporter assays. Finally, we testified that FOXD2-AS1 could competitively sponge miR-760 and further upregulated the E2F3 expression to play a vital part in cholangiocarcinoma. This research revealed that lncRNA FOXD2-AS1 could enhance CCA malignant progression through regulating the miR-760/E2F3 axis and was expected to be a prognostic biomarker and therapeutic target for cholangiocarcinoma.

LncRNA FOXD2-AS1 knockdown inhibits the resistance of human osteosarcoma cells to cisplatin by inhibiting miR-143 expression.

The aim of this study was to explore the effect of long non-coding ribonucleic acid (lncRNA) FOXD2-adjacent opposite strand RNA 1 (FOXD2-AS1) on the sensitivity of osteosarcoma cells to cisplatin and its possible underlying mechanism. Our findings might help to provide a certain reference for clinically preventing the drug resistance of osteosarcoma cells. Cisplatin with a certain concentration gradient was used to induce the stable acquired resistance of human osteosarcoma U2-OS cell line. Subsequently, the expression level of lncRNA FOXD2-AS1 was determined in osteosarcoma cells in non-resistance group (Control group) and Cisplatin-resistance group (Cisplatin-RES group), respectively. Next, the cell line with stable lncRNA FOXD2-AS1 knockdown was constructed in Cisplatin-RES group using small interfering RNA (siRNA). The effects of stable knockdown of lncRNA FOXD2-AS1 on the proliferation of human osteosarcoma cells and the half-maximal inhibitory concentration (IC50) of cisplatin were detected by Cell Counting Kit-8 (CCK-8) assay. 5-ethynyl-2'-deoxyuridine (EdU) staining was performed to measure deoxyribonucleic acid (DNA) replication level in each group of cells. The protein expression levels of apoptosis-associated genes B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) in each group of cells were measured via Western blotting. The migration and invasion abilities of cells in each group were determined using wound-healing assay and transwell assay. In addition, the expression of micro RNA (miR)-143 in each group of cells was detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Compared with Control group, the expression level of lncRNA FOXD2-AS1 rose significantly in cells in Cisplatin-RES group (p<0.05). Knockdown of FOXD2-AS1 evidently decreased the IC50 of cisplatin in human osteosarcoma cells (p<0.05). According to EdU staining results, the knockdown of FOXD2-AS1 distinctly inhibited the proliferation of osteosarcoma cells (p<0.05). Western blotting results demonstrated that the knockdown of FOXD2-AS1 remarkably upregulated the expression of pro-apoptotic protein Bax and repressed that of anti-apoptotic protein Bcl-2 in drug-resistant human osteosarcoma cells (p<0.05). Moreover, the knockdown of FOXD2-AS1 significantly weakened the migration and invasion abilities of drug-resistant human osteosarcoma cells (p<0.05). Finally, it was found that the expression level of miR-143 was distinctly elevated in drug-resistant human osteosarcoma cells after knockdown of FOXD2-AS1 (p<0.05). LncRNA FOXD2-AS1 knockdown inhibits the resistance of human osteosarcoma cells to cisplatin, promotes their apoptosis and weakens their invasion and migration abilities. The possible underlying mechanism may be related to the inhibition of miR-143 expression by lncRNA FOXD2-AS1 in drug-resistant cell lines.

Dysregulation of FOXD2-AS1 promotes cell proliferation and migration and predicts poor prognosis in oral squamous cell carcinoma: a study based on TCGA data.

FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) plays an important role in the pathogenesis of some cancers. However, its functional role in oral squamous cell carcinoma (OSCC) remains largely unknown. In this study, we conducted expressional and functional analyses of FOXD2-AS1 using data from the Cancer Genome Atlas (TCGA) and in vitro OSCC assays. FOXD2-AS1 dysregulation was remarkably associated with radiation therapy, anatomic location, high histologic grade, and lymphovascular invasion (P < 0.05). A nomogram based on FOXD2-AS1 expression was constructed for use as a diagnostic indicator for OSCC patients, and multivariate cox regression analysis showed that FOXD2-AS1 expression was an independent prognostic factor for OSCC patients. KEGG, gene set enrichment analysis, and immune infiltration evaluations indicated that FOXD2-AS1 was involved in tumor progression via epithelial-to-mesenchymal transition and cell cycle regulation and was negatively associated with mast cell, DCs, iDCs, and B cells. FOXD2-AS1 silencing suppressed the proliferation and migration of Cal27 cells. Our findings showed that an aberrantly high FOXD2-AS1 expression predicts poor prognosis in OSCC; FOXD2-AS1 may act as an oncogenic protein by regulating cell proliferation and migration and may suppress adaptive immunity by modulating the number and function of antigen-presenting cells.

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

Background and aims: Long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is aberrantly expressed in various cancers and associated with cancer progression. A comprehensive meta-analysis was performed based on published literature and data in the Gene Expression Omnibus database, and then the Cancer Genome Atlas (TCGA) dataset was used to assess the clinicopathological and prognostic value of FOXD2-AS1 in cancer patients.Methods: Gene Expression Omnibus databases of microarray data and published articles were used for meta-analysis, and TCGA dataset was also explored using the GEPIA analysis program. Hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the role of FOXD2-AS1 in cancers.Results: This meta-analysis included 21 studies with 2391 patients and 25 GEO datasets with 3311 patients. The pooled HRs suggested that highly expressed FOXD2-AS1 expression was correlated with poor overall survival (OS) and disease-free survival (DFS). Similar results were obtained by analysis of TCGA data for 9502 patients. The pooled results also indicated that FOXD2-AS1 expression was associated with bigger tumor size and advanced TNM stage, but was not related to age, gender, differentiation and lymph node metastasis.Conclusion: The present study demonstrated that FOXD2-AS1 is closely related to tumor size and TNM stage. Additionally, increased FOXD2-AS1 was a risk factor of OS and DFS in cancer patients, suggesting FOXD2-AS1 may be a potential biomarker in human cancers.

Silencing of long non-coding RNA FOXD2-AS1 inhibits the progression of gallbladder cancer by mediating methylation of MLH1.

Evidence has documented the tumor-promoting properties of long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) in many cancers. However, little is known about its role in gallbladder cancer. Here, we aimed to characterize the functional relevance of lncRNA FOXD2-AS1 in gallbladder cancer and the possible mechanisms associated with methylation of MutL homolog-1 (MLH1). Initially, microarray-based gene expression profiling of gallbladder cancer was employed to identify differentially expressed lncRNAs. Next, the expression of lncRNA FOXD2-AS1 was examined, and the cell line presenting with the highest lncRNA FOXD2-AS1 expression was selected for subsequent experimentation. Then, the interaction between lncRNA FOXD2-AS1 and MLH1 was identified. The effect of lncRNA FOXD2-AS1 on proliferation, migration, invasion, and apoptosis as well as tumorigenicity of transfected GBC-SD cells was examined with gain- and loss-of-function experiments. We found that lncRNA FOXD2-AS1 was highly expressed, while MLH1 was poorly expressed in gallbladder cancer cells. Besides, lncRNA FOXD2-AS1 could promote MLH1 methylation by recruiting DNMT1 to the MLH1 promoter, and consequently inhibit MLH1 transcription. Silencing of lncRNA FOXD2-AS1 or overexpression of MLH1 inhibited gallbladder cancer cell proliferation, invasion, and migration, while facilitating cell apoptosis in vitro as well as retarding tumor growth in vivo. Thus, silencing of lncRNA FOXD2-AS1 suppressed the progression of gallbladder cancer via upregulation of MLH1 by inhibiting MLH1 promoter methylation. These findings present lncRNA FOXD2-AS1 knockdown as a potential candidate for the treatment of gallbladder cancer.

LncRNA FOXD2-AS1 promotes hemangioma progression through the miR-324-3p/PDRG1 pathway

BackgroundLong non-coding RNAs (lncRNAs) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) are reported could function as tumor promoter in several cancers. However, its role in hemangioma was not reported to yet.MethodsExpression level of FOXD2-AS1 in hemangioma tissues and cells was explored using quantitative reverse-time PCR. Cell counting kit-8 (CCK-8) assay, colony formation assay, wound-healing assay, and transwell invasion assay were conducted to measure the roles of FOXD2-AS1. In addition, the levels of markers for proliferation and Epithelial-Mesenchymal Transition were investigated. Connection of FOXD2-AS1 and mcroRNA-324-3p (miR-324-3p) or miR-324-3p and p53 and DNA damage regulated 1 (PDRG1) was analyzed with bioinformatic analysis method and dual-luciferase activity reporter assay.ResultsHere, we found that FOXD2-AS1 was highly expressed in proliferating-phase hemangioma tissues compared with the involuting-phase hemangioma tissues. Functionally, FOXD2-AS1 knockdown suppressed cell proliferation, colony formation, migration, and invasion in vitro. Conversely, overexpression of FOXD2-AS1 promoted tumor growth in vitro. Mechanistically, FOXD2-AS1 inversely regulated miR-324-3p abundance in hemangioma cells. We also found FOXD2-AS1 acted as a competing endogenous RNA (ceRNA) by directly sponging miR-324-3p to regulate PDRG1 expression. In addition, the knockdown of PDRG1 reversed the stimulation effects of FOXD2-AS1 overexpression on HA cells.ConclusionTo conclude, our study sheds novel light on the biological roles of FOXD2-AS1 in hemangioma, which may help the development of targeted therapy method for cancer.

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

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-H-tetrazolium 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 of miR-760 with consequent upregulation of HDGF. The FOXD2-AS1–miR-760–HDGF axis might harbor promising targets for novel treatment strategies of cervical cancer.

FOXD2-AS1 Predicts Dismal Prognosis for Oral Squamous Cell Carcinoma and Regulates Cell Proliferation

The roles of long noncoding RNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) in oral squamous cell carcinoma (OSCC) remain largely unknown. Here, the Atlas of Noncoding RNAs in Cancer online database was utilized to analyze the expression and clinical significance of FOXD2-AS1 in OSCC. Then, the cell proliferation of FOXD2-AS1-silenced OSCC cells (CAL-27) was assessed by MTT and clone formation experiments. FOXD2-AS1-coexpressed genes were enriched and analyzed via circlncRNAnet and Metascape tools. Finally, key molecules of the signal pathways of the aforementioned coexpressed genes were verified by western blotting. We found that FOXD2-AS1 was significantly highly expressed in OSCC tissues, and correlated with poor pathological grade and prognosis in patients with OSCC. Cell viability and clone formation ability were significantly inhibited after the knockdown of FOXD2-AS1. A total of 32 coexpressed genes of FOXD2-AS1 were identified, and those genes were enriched in the cell cycle. In conclusion, FOXD2-AS1 may be served as a potential prognostic indicator and therapeutic target for OSCC.

Long noncoding RNA FOXD2-AS1 promotes glioma cell cycle progression and proliferation through the FOXD2-AS1/miR-31/CDK1 pathway.

Long noncoding RNAs (lncRNAs) are vital mediators involved in cancer progression. Previous studies confirmed that FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is upregulated in tumor diseases. The potential influence of FOXD2-AS1 in glioma progression, however, remains unknown. In this paper, FOXD2-AS1 was found to be upregulated in glioma tissues. Its level was linked with glioma stage. Moreover, glioma patients expressing high level of FOXD2-AS1 suffered worse prognosis. Biological functions of FOXD2-AS1 in glioma cells were analyzed through integrative bioinformatics and TCGA RNA sequencing data analysis. Pathway enrichment analysis uncovered that FOXD2-AS1 was mainly linked with cell cycle regulation in both low-grade glioma and glioblastoma. Further experiments demonstrated that silence of FOXD2-AS1 inhibited proliferation, arrested cell cycle and downregulated cyclin-dependent kinase 1 (CDK1) in human glioma cells. Dual-luciferase reporter assay confirmed that FOXD2-AS1 upregulated CDK1 by sponging miR-31. Rescue assays were performed and confirmed the regulatory loop FOXD2-AS1/miR-31/CDK1 in glioma. Collectively, our results indicated that the FOXD2-AS1/miR-31/CDK1 axis influenced glioma progression, providing a potential new target for glioma patients.

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

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.

Long non‑coding RNA FOXD2‑AS1/miR‑150‑5p/PFN2 axis regulates breast cancer malignancy and tumorigenesis.

Breast cancer (BC) is a common cancer and leading cause of cancer‑associated mortality in women. Abnormal expression of long non‑coding RNA FOXD2 adjacent opposite strand RNA1 (FOXD2‑AS1) was associated with the development of a number of tumors. However, whether FOXD2‑AS1 is dysregulated in BC and its underlying mechanisms remain unclear. In the present study, it was identified that FOXD2‑AS1 expression was upregulated in BC tissue, cell lines and sphere subpopulation. Additionally, the abnormal upregulation of FOXD2‑AS1 predicted poor prognosis in patients with BC. Furthermore, downregulation of FOXD2‑AS1 decreased cell proliferation, and migratory and invasive abilities in BC cells, and decreased the growth of transplanted tumors invivo. Downregulation of FOXD2‑AS1 decreased the percentage of CD44 antigen+/signal transducer CD24- in breast cancer stem cell(BCSC) cells, and decreased the expression of numerous stem factors, including Nanog, octamer‑binding transcription factor4(Oct4), and sex determining region Y‑box2(SOX2), and inhibited the epithelial‑mesenchymal transition process. FOXD2‑AS1 was identified to be primarily located in the cytoplasm. Using bioinformatics analysis, a reporter gene assay and reverse transcription‑polymerase chain reaction assays, it was demonstrated that microRNA (miR)‑150‑5p was able to bind directly with the 3'‑untranslated region of FOXD2‑AS1 and PFN2 mRNA. miR‑150‑5p mimics decreased the cell proliferation, migration and invasion of BC cells. FOXD2‑AS1 knockdown significantly inhibited the miR‑150‑5p inhibitor‑induced increase in Nanog, Oct4 and SOX2 expression. The miR‑150‑5p inhibitor‑induced increase in N‑cadherin, and decrease in E‑cadherin and vimentin was inhibited by FOXD2‑AS1 knockdown. Profilin2 (PFN2) expression was significantly upregulated in BC tissues. Additionally, the abnormal upregulation of PFN2 was associated with poor prognosis in patients with BC. FOXD2‑AS1 and PFN2 expression was positively correlated. Collectively, the present results demonstrated the role of the FOXD2‑AS1/miR‑150‑5p/PFN2 axis in the development of BC, and provides novel targets for the treatment of BC, and potential biomarkers for diagnosis and prognosis of BC.

FoxD2-AS1 is a prognostic factor in glioma and promotes temozolomide resistance in a O6-methylguanine-DNA methyltransferase-dependent manner.

Glioma is the most common brain tumor with a dismal prognosis. While temozolomide (TMZ) based chemotherapy significantly improves survival in glioma patients, resistance against this compound commonly leads to glioma treatment failure. Overexpression of long-noncoding RNA (LncRNA) FoxD2 adjacent opposite strand RNA 1 (FoxD2-AS1) was identified to promote glioma development, but the role in TMZ resistance remains unclear. In this paper, we found that FoxD2-AS1 was overexpressed in recurrent glioma, high FoxD2-AS1 expression was significantly correlated with poor patient outcome. Methylation of O6-methylguanine-DNA methyltransferase (MGMT) is significantly less frequent in high FoxD2-AS1 expression patients. Knockdown of FoxD2-AS1 decreased the proliferation, metastatic ability of glioma cells and promote the sensitivity to TMZ in glioma cells. Furthermore, knockdown of FoxD2-AS1 induced hypermethylation of the promoter region of MGMT. Our data suggested that FoxD2-AS1 is a clinical relevance LncRNA and mediates TMZ resistance by regulating the methylation status of the MGMT promoter region.

FOXD2-AS1 correlates with the malignant status and regulates cell proliferation, migration, and invasion in cutaneous melanoma.

Long noncoding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) has been shown to be dysregulated in several types of human cancer. However, the role of FOXD2-AS1 in cutaneous melanoma was still unclear. In our study, FOXD2-AS1 expression has been found to be upregulated in cutaneous melanoma tissue specimens and cell lines compared with that in normal tissue specimens and normal human epidermal melanocyte, respectively. Furthermore, high expression of FOXD2-AS1 was obviously correlated with deep Breslow thickness, present ulceration, high Clark level and distant metastasis in cutaneous melanoma patients. However, there were no statistical associations between FOXD2-AS1 expression and cutaneous melanoma patients' disease-free survival and overall survival. The results of loss-of-function study showed that inhibition of FOXD2-AS1 suppresses cutaneous melanoma cell proliferation, migration and invasion through regulating phospho-Akt expression. In conclusion, FOXD2-AS1 is associated with clinical progression in cutaneous melanoma patients, and functions as oncogenic lncRNA in cutaneous melanoma cells.

Long non-coding RNA FOXD2-AS1 plays an oncogenic role in hepatocellular carcinoma by targeting miR‑206.

Recently, long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA1 (FOXD2-AS1) has been recognized to function as an oncogene in several human tumors, and FOXD2‑AS1 dysregulation has been closely associated with carcinogenesis and tumor progression. Nevertheless, the correlation between the aberrant expression of FOXD2‑AS1 and the prognosis of hepatocellular carcinoma (HCC) has not yet been elucidated. In the present study, FOXD2‑AS1 was found to be overexpressed in HCC tissues, and FOXD2‑AS1 overexpression resulted in significantly shortened patient survival. FOXD2‑AS1 overexpression enhanced the viability and metastasis of HCC cells invitro and in vivo, as revealed by MTT, wound healing and cell migration assays. In addition, mechanistic studies revealed that FOXD2‑AS1 upregulated the expression of the miR‑206 target gene annexinA2 (ANXA2) by acting as a miR‑206 sponge. In summary, FOXD2‑AS1 was concluded to function as an oncogene in HCC and to upregulate ANXA2 expression in part by 'sponging' miR‑206.