Down-regulation of long non-coding RNA FOXD3 antisense RNA 1 (FOXD3-AS1) inhibits cell proliferation, migration, and invasion in malignant glioma cells.

in American journal of translational research by Zhen-Hua Chen, Hong-Kang Hu, Chen-Ran Zhang, Cheng-Yin Lu, Yi Bao, Zheng Cai, Yong-Xiang Zou, Guo-Han Hu, Lei Jiang

TLDR

  • This study found that a type of RNA called FOXD3-AS1 is more likely to be found in high-grade glioma (a type of brain tumor) than in low-grade glioma or normal brain tissue. It also found that patients with lower levels of FOXD3-AS1 had a better chance of surviving. The study then looked at how FOXD3-AS1 affects the growth and movement of glioma cells and found that it promotes the occurrence and development of glioma. The study suggests that FOXD3-AS1 could be a target for treatment of glioma.

Abstract

Growing evidence indicates that long non-coding RNAs (lncRNAs) play key roles in cancer initiation and progression. However, little is known about the therapeutic significance of lncRNAs in glioma. In this study, we explored the tumorigenic role of a classical lncRNA, FOXD3 antisense RNA 1 (FOXD3-AS1) in glioma. Systemic analysis of the patient specimens and clinical data showed that FOXD3-AS1 was markedly up-regulated in high-grade glioma tissues (WHO grade III-IV) compared with that in low-grade glioma (WHO grade I-II) and normal brain tissues (both P<0.01), and patients with low FOXD3-AS1 expression had grater survival probability. Multivariate regression analysis showed that increased FOXD3-AS1 expression was a significant independent indicator of poor prognosis in glioma patients (P=0.034). To understand the tumorigenic mechanism of FOXD3-AS1, the expression pattern and functional role of FOXD3-AS1 in glioma were detected using real-time PCR and Smart Silencer-mediated knockdown study. In related cell biological assays, we discovered that FOXD3-AS1 knockdown significantly inhibited cell proliferation, induced cell cycle S-phase arrest, and impaired cell migration and invasion in malignant glioma cells. As expected, we also found that the expression of FOXD3-AS1 was positively correlated with FOXD3 mRNA. Knockdown of FOXD3-AS1 reduced the protein level of FOXD3 in cultured U251 and A172 cell lines. These results suggest that FOXD3-AS1 is an oncogenic lncRNA, which may promote the occurrence and development of glioma through transcriptional regulation of FOXD3.

Overview

  • The study explores the tumorigenic role of FOXD3 antisense RNA 1 (FOXD3-AS1) in glioma
  • Systemic analysis of patient specimens and clinical data showed that FOXD3-AS1 was up-regulated in high-grade glioma tissues compared with low-grade glioma and normal brain tissues, and patients with low FOXD3-AS1 expression had greater survival probability
  • Multivariate regression analysis showed that increased FOXD3-AS1 expression was a significant independent indicator of poor prognosis in glioma patients

Comparative Analysis & Findings

  • FOXD3-AS1 knockdown significantly inhibited cell proliferation, induced cell cycle S-phase arrest, and impaired cell migration and invasion in malignant glioma cells
  • The expression of FOXD3-AS1 was positively correlated with FOXD3 mRNA, and knockdown of FOXD3-AS1 reduced the protein level of FOXD3 in cultured U251 and A172 cell lines
  • These results suggest that FOXD3-AS1 is an oncogenic lncRNA, which may promote the occurrence and development of glioma through transcriptional regulation of FOXD3

Implications and Future Directions

  • The study highlights the potential of FOXD3-AS1 as a therapeutic target for glioma
  • Future research should focus on developing targeted therapies against FOXD3-AS1 to inhibit its oncogenic effects
  • Additional studies are needed to validate the findings and explore the underlying mechanisms of FOXD3-AS1 in glioma
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