Dataset Information

Risk-Associated Long Noncoding RNA FOXD3-AS1 Inhibits Neuroblastoma Progression by Repressing PARP1-Mediated Activation of CTCF.

ABSTRACT: Neuroblastoma (NB) is the most common extracranial tumor in childhood. Recent studies have implicated the emerging roles of long noncoding RNAs (lncRNAs) in tumorigenesis and aggressiveness. However, the functions and targets of risk-associated lncRNAs in NB progression still remain to be determined. Herein, through mining of public microarray datasets, we identify lncRNA forkhead box D3 antisense RNA 1 (FOXD3-AS1) as an independent prognostic marker for favorable outcome of NB patients. FOXD3-AS1 is downregulated in NB tissues and cell lines, and ectopic expression of FOXD3-AS1 induces neuronal differentiation and decreases the aggressiveness of NB cells in vitro and in vivo. Mechanistically, as a nuclear lncRNA, FOXD3-AS1 interacts with poly(ADP-ribose) polymerase 1 (PARP1) to inhibit the poly(ADP-ribosyl)ation and activation of CCCTC-binding factor (CTCF), resulting in derepressed expression of downstream tumor-suppressive genes. Rescue experiments indicate that FOXD3-AS1 harbors tumor-suppressive properties by inhibiting the oncogenic roles of PARP1 or CTCF and plays crucial roles in all-trans-retinoic-acid-mediated therapeutic effects on NB. Administration of FOXD3-AS1 construct or siRNAs against PARP1 or CTCF reduces the tumor growth and prolongs the survival of nude mice. These findings suggest that as a risk-associated lncRNA, FOXD3-AS1 inhibits the progression of NB through repressing PARP1-mediated CTCF activation.

SUBMITTER: Zhao X

PROVIDER: S-EPMC5910666 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Publications

Risk-Associated Long Noncoding RNA FOXD3-AS1 Inhibits Neuroblastoma Progression by Repressing PARP1-Mediated Activation of CTCF.

Zhao Xiang X Li Dan D Huang Dandan D Song Huajie H Mei Hong H Fang Erhu E Wang Xiaojing X Yang Feng F Zheng Liduan L Huang Kai K Tong Qiangsong Q

Molecular therapy : the journal of the American Society of Gene Therapy 20171222 3

Neuroblastoma (NB) is the most common extracranial tumor in childhood. Recent studies have implicated the emerging roles of long noncoding RNAs (lncRNAs) in tumorigenesis and aggressiveness. However, the functions and targets of risk-associated lncRNAs in NB progression still remain to be determined. Herein, through mining of public microarray datasets, we identify lncRNA forkhead box D3 antisense RNA 1 (FOXD3-AS1) as an independent prognostic marker for favorable outcome of NB patients. FOXD3-A ...[more]

PMID: 29398485

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Project description:Long non‑coding RNA forkhead box D3 antisense RNA 1 (FOXD3‑AS1) functions as an oncogenic regulator in several types of cancer, including breast cancer, glioma and cervical cancer. However, the effects and mechanisms underlying FOXD3‑AS1 in cervical cancer (CC) are not completely understood. The present study aimed to investigate the biological functions and potential molecular mechanisms underlying FOXD3‑AS1 in CC progression. Reverse transcription‑quantitative PCR was performed to detect FOXD3‑AS1, microRNA (miR)‑128‑3p and LIM domain kinase 1 (LIMK1) expression levels in CC tissues and cells. Immunohistochemical staining and western blotting were conducted to assess LIMK1 protein expression levels in CC tissues and cells, respectively. Cell Counting Kit‑8 and BrdU assays were used to determine the role of FOXD3‑AS1 in regulating cell proliferation. CC cell migration and invasion were assessed by performing Transwell assays. Dual‑luciferase reporter assays were conducted to verify the binding between miR‑128‑3p and FOXD3‑AS1. FOXD3‑AS1 expression was significantly increased in CC tissues and cell lines compared with adjacent healthy tissues and normal cervical epithelial cells, respectively. High FOXD3‑AS1 expression was significantly associated with poor differentiation of tumor tissues, increased tumor size and positive lymph node metastasis. FOXD3‑AS1 overexpression significantly increased CC cell proliferation, migration and invasion compared with the negative control (NC) group, whereas FOXD3‑AS1 knockdown resulted in the opposite effects compared with the small interfering RNA‑NC group. Moreover, the results demonstrated that FOXD3‑AS1 targeted and negatively regulated miR‑128‑3p, which indirectly upregulated LIMK1 expression. Therefore, the present study demonstrated that FOXD3‑AS1 upregulated LIMK1 expression via competitively sponging miR‑128‑3p in CC cells, promoting CC progression.

Dataset Information

Risk-Associated Long Noncoding RNA FOXD3-AS1 Inhibits Neuroblastoma Progression by Repressing PARP1-Mediated Activation of CTCF.

Publications

Risk-Associated Long Noncoding RNA FOXD3-AS1 Inhibits Neuroblastoma Progression by Repressing PARP1-Mediated Activation of CTCF.

Similar Datasets

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