Although lncRNAs are recognized to contribute to the development of oral squamous-cell carcinoma (OSCC), their exact function in invasion and cell migration is not clear. In this research, we explored the molecular and cellular mechanisms of FOXD2-AS1 in OSCC. Prognostic and bioinformatics analyses were used to test for the differential expression of FOXD2-AS1-PLOD1. Following FOXD2-AS1 suppression or overexpression, changes in cell viability were measured using the CCK-8 test; changes in cell migration and invasion abilities were measured using the migration and the Transwell assay. The expression of associated genes and proteins was found using Western blot and RT-qPCR. Analysis of luciferase reporter genes was done to look for regulatory connections between various molecules. The FOXD2-AS1-PLOD1 pair, which was highly expressed in OSCC, was analyzed and experimentally verified to be closely related to the prognosis of OSCC, and a nomogram model and correction curve were constructed. The inhibition of FOXD2-AS1 resulted in the reduction of cell activity, migration, invasion ability and changes in genes related to invasion and migration. In vivo validation showed that inhibition of FOXD2-AS1 expression slowed tumor growth, and related proteins changed accordingly. The experiments verified that FOXD2-AS1 negatively regulated miR-185-5 p and that miR-185-5 p negatively regulated PLOD1. In addition, it was found that the expression of PLOD1, p-Akt and p-mTOR proteins in OSCC cells was reduced by the inhibition of FOXD2-AS1, and FOXD2-AS1 and PLOD1 were closely related to the Akt/mTOR pathway. Increased expression of FOXD2-AS1 promotes OSCC growth, invasion and migration, which is important in part by targeting miR-185-5 p/PLOD1/Akt/mTOR pathway activity.

FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is a long non-coding RNA being transcribed from a locus on chromosome 1p33. This transcript has been found to be up-regulated in tumor samples of almost all types of malignancies in association with a significant increase in malignant features. FOXD2-AS1 can affect activity of PI3K/AKT, AKT/mTOR, Hippo/YAP, Notch, NRf2, Wnt/β-catenin, NF-ƙB and ERK/MAPK pathways. Furthermore, it can enhance stem cell properties in cancer cells and prompt epithelial-mesenchymal transition. It is also involved in induction of resistance to a variety of anticancer agents such as adriamycin, cisplatin, 5-fluorouracil, temozolomide and gemcitabine. This article summarizes the impact of FOXD2-AS1 in diverse human disorders.

The healing of skin wounds is a highly coordinated multi-step process that occurs after trauma including surgical incisions, thermal burns, and chronic ulcers. In this study, the authors investigated lncRNA FOXD2-AS1 function in adipose mesenchymal exosomes from ADMSCs that were successfully extracted. Highly expressed lncRNA FOXD2-AS1 in ADMSCs-exosomes accelerated HaCaT cell migration and proliferation. LncRNA FOXD2-AS1 negatively targeted miR-185-5p, and miR-185-5p negatively targeted ROCK2. Highly expressed lncRNA FOXD2-AS1 in ADMSCs-exosomes promoted HaCaT cell migration and proliferation via down-regulating miR-185-5p and further up-regulating ROCK2. In conclusion, LncRNA FOXD2-AS1 overexpression in ADMSCs derived exosomes might accelerate HaCaT cell migration and proliferation via modulating the miR-185-5p/ROCK2 axis.

UNASSIGNED: Colorectal cancer (CRC) is still considered one of the prevalent cancers worldwide. Investigation of potential biomarkers for early detection of CRC is essential for the effective management of patients using therapeutic strategies. Considering that, this study was aimed to examine the changes in lncRNA FOXD2-AS1 expression through colorectal tumorigenesis.
UNASSIGNED: Fifty CRC tumor tissues and fifty adjacent normal tissue samples were prepared and involved in the current study. Total RNA was extracted from the samples and then reverse transcribed to complementary DNA. Next, the expression levels of lncRNA FOXD2-AS1 were evaluated using real-time PCR in CRC samples compared to normal ones. Also, receiver operating characteristic curve analysis was used to evaluate the diagnostic value of FOXD2-AS1 for CRC.
UNASSIGNED: The obtained results showed that the expression level of FOXD2-AS1 gene was significantly (p<0.0001) up-regulated in tumor tissues compared to normal marginal tissues. Also, a significant correlation was observed between higher the expression of FOXD2-AS1and the differentiation of tumor cells. Furthermore, ROC curve analysis estimated an AUC value of 0.59 for FOXD2-AS1, suggesting its potential as a diagnostic target.
UNASSIGNED: Taken together, the current study implied that tissue-specific upregulation of lncRNA FOXD2-AS1 might be appropriate diagnostic biomarkers for CRC. Nonetheless, more studies are needed to validate these results and further illustrate FOXD2-AS1 function through colorectal tumorigenesis.

OBJECTIVE: We have previously characterized oncogenic properties of IGF2BP1 in HCC, and its regulation by short noncoding RNAs (ncRNAs). Recent evidence suggests that IGF2BP1 itself may regulate long ncRNAs (lncRNAs). Therefore, this study aimed at exploring the interplay between IGF2BP1 and various upstream and downstream ncRNAs and its link to HCC pathogenesis.
METHODS: Bioinformatic analysis was used to identify up- and downstream ncRNAs interacting with IGF2BP1. Huh-7 cells were transfected with siRNAs against IGF2BP1 and microRNA mimics. Relative gene expression was determined using RTqPCR and IGF2BP1 protein was quantified by western blot. Luciferase binding assay was used to explore the targeting of IGF2BP1 3\'UTR. HCC tumorigenesis was measured by MTT assay, BrdU-incorporation assay, colony-forming assay, and scratch assay.
RESULTS: Bioinformatic analysis identified three oncogenic lncRNAs - namely H19, FOXD2-AS1, and SNHG3 - potentially regulated by IGF2BP1. Knockdown of IGF2BP1 decreased the expression of all three oncogenic lncRNAs and inhibited malignant cell behaviors. miR-186 was revealed as a possible upstream regulator of IGF2BP1. miR-186 mimics decreased IGF2BP1 mRNA and protein levels. miR-186 was significantly lower while IGF2BP1 was elevated in cancerous tissues from ten HCC patients compared to five healthy controls. In addition, miR-186 mimics caused a downregulation of the oncogenic lncRNAs H19, SNHG3, and FOXD2-AS1 and a concomitant decrease in cell viability, proliferation, migration, and clonogenicity.
CONCLUSIONS: miR-186 may exert tumor suppressor effects in HCC by repressing oncogenic lncRNAs H19, SNHG3, and FOXD2-AS1 through its effect on IGF2BP1.

OBJECTIVE: A growing number of evidences has revealed that long non-coding RNAs (lncRNAs) have vital effect in the pathogenesis of esophageal squamous cell carcinoma (ESCC). In our work, we found that lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) was significantly increased in clinical ESCC samples and cell lines.
METHODS: The biological effect of FOXD2-AS1 on EC109 and KYSE150 cells showed that the low expression of FOXD2-AS1 inhibited the proliferation through CCK8 and colony formation assays, invasion by transwell chamber test, migration abilities by wound healing assay, and enhance apoptosis rates by flow cytometry assay.
RESULTS: Through bioinformatics analysis and luciferase reporter assays, microRNA (miR)-204-3p was proved to be a target of FOXD2-AS1. We further confirmed that FOXD2-AS1 was the upstream inhibitor of miR-204-3p and the down-regulation of miR-204-3p reversed the repressive effects of low expression of FOXD2-AS1 on ESCC progression. In addition, inhibition of FOXD2-AS1 effectively suppressed the tumor growth.
CONCLUSIONS: In general, our results suggested that FOXD2-AS1 may be of vital therapeutic importance for the treatment of ESCC patients.

Long noncoding RNAs (lncRNAs) play critical roles in tumor progression regulation, including osteosarcoma. Evidence indicates that N6-methyladenosine (m6A) modification modulates mRNA stability to regulate osteosarcoma tumorigenesis. Here, present research aims to detect the roles of m6A-modified lncRNA FOXD2-AS1 in the osteosarcoma pathophysiological process. Clinical data unveiled that osteosarcoma patients with higher FOXD2-AS1 expression had a poorer overall survival rate compared to those with lower FOXD2-AS1 expression. Functional research illuminated that FOXD2-AS1 accelerated the migration, proliferation and tumor growth in vitro and in vivo. Mechanistically, a remarkable m6A-modified site was found on the 3\'-UTR of FOXD2-AS1, and m6A methyltransferase WTAP (Wilms\' tumor 1 associated protein) promoted the methylation modification, thus enhancing the stability of FOXD2-AS1 transcripts. Furthermore, FOXD2-AS1 interacted with downstream target FOXM1 mRNA through m6A sites, forming a FOXD2-AS1/m6A/FOXM1 complex to heighten FOXM1 mRNA stability. In conclusion, these findings propose a novel regulatory mechanism in which m6A-modified FOXD2-AS1 accelerates the osteosarcoma progression through m6A manner, which may provide new concepts for osteosarcoma tumorigenesis.

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.

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.

OBJECTIVE: Gastric cancer (GC) is one of the most frequent tumors worldwide and identification of a sensitive and specific prognostic biomarker is of great importance. Long non-coding RNAs (lncRNAs) play crucial roles in tumorigenesis of various malignancies. In the present study, we investigated lncRNA FOXD2-AS1 expression in gastric tumors and assessed its potential as a prognostic biomarker.
METHODS: A total of 95 tumor and corresponding adjacent non-tumor tissue specimens were collected from patients with GC from Imam Reza hospital, Tabriz, Iran. Total RNA was isolated and FOXD2-AS1 expression was measured using quantitative reverse transcriptase (qRT)-PCR.
RESULTS: FOXD2-AS1 was significantly upregulated in tumor samples as compared to non-tumor tissues (P < 0.0001). In addition, higher expression of FOXD2-AS1 was significantly associated with lymph node metastasis and Helicobacter pylori infection. The receiver operating characteristic (ROC) curve analysis revealed that FOXD2-AS1 might be served as a potential prognostic biomarker for GC.
CONCLUSIONS: FOXD2-AS1 is upregulated in gastric tumors and can be used as a valuable biomarker in the prognosis of patients with GC.