Down-regulation of long non-coding RNA FOXD3 antisense RNA 1 (FOXD3-AS1) inhibits cell proliferation, migration, and invasion in malignant glioma cells.
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.
Department of Neurosurgery, Changzheng Hospital, Second Military Medical UniversityShanghai, China; Department of Neurosurgery, The First People's Hospital of Nantong, Medical School of Nantong UniversityJiangsu Province, China.
Zhen-Hua
ZH
Chen
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University Shanghai, China.
Hong-Kang
HK
Hu
Department of Pediatric Neurosurgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Chen-Ran
CR
Zhang
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University Shanghai, China.
Cheng-Yin
CY
Lu
Department of Endocrinology, Changzheng Hospital, Second Military Medical University Shanghai, China.
Yi
Y
Bao
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University Shanghai, China.
Zheng
Z
Cai
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University Shanghai, China.
Yong-Xiang
YX
Zou
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University Shanghai, China.
Guo-Han
GH
Hu
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University Shanghai, China.
Lei
L
Jiang
FOXD3; FOXD3-AS1; Long non-coding RNA; glioma