Long Non-Coding RNA FOXD1-AS1 Promotes the Progression and Glycolysis of Nasopharyngeal Carcinoma by Sustaining FOXD1 Expression

Abstract

Background: Increasing evidence have emphasized the importance of long non-coding RNAs (lncRNAs) in various human cancers progression. Forkhead box D1 antisense RNA1 (FOXD1-AS1) is a novel lncRNA and plays vital regulatory role in diverse biological processes of cancers. However, the biological function, molecular mechanism and clinical significance of FOXD1-AS1 in nasopharyngeal carcinoma is still unknown.Methods: Comprehensive bioinformatics analysis and qRT-PCR was conducted to detect the expression level of FOXD1-AS1. Loss-of-function and gain-of-function experiments were performed to verify the functions of FOXD1-AS1 in proliferation, migration, invasion, apoptosis and glycolysis of nasopharyngeal carcinoma in vitro and in vivo. Further bioinformatics analysis and experiments were carried out to explore the underlying molecular mechanisms of FOXD1-AS1. Results: FOXD1-AS1 was significantly overexpressed in nasopharyngeal carcinoma and associated with poor survival in patients. Knockdown of FOXD1-AS1 significantly inhibited cell proliferation, migration, invasion and glycolysis, and promotes apoptosis in nasopharyngeal carcinoma, whereas over-expression of FOXD1-AS1 has the opposite effect. Mechanistically, we found that FOXD1-AS1 could upregulate the expression of FOXD1 through stabilizing the FOXD1 expression at mRNA and protein levels, and FOXD1 increased the glycolysis level by transcriptionally upregulating the expression of LDHA, PKM and ENO1, thus playing an oncogenic role in nasopharyngeal carcinoma progression. Conclusion: FOXD1-AS1 plays a critical regulatory role in nasopharyngeal carcinoma. The identified FOXD1-AS1/FOXD1 axis may serve as a potential prognostic biomarker and therapeutic target for patients with nasopharyngeal carcinoma.

FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2

“…Recent studies have demonstrated that upregulated FOXD1 is related to the metastasis status and adverse clinical outcomes of OSCC [ 10 ]. In addition, FOXD1-AS1 can enhance the proliferation and decrease the apoptosis of nasopharyngeal carcinoma by upregulating FOXD1 expression [ 21 ]. These results indicate that FOXD1 can behave as an oncogene in cancer.…”

FOXD1 Promotes EMT and Cell Stemness of Head and Neck Squamous Cell Carcinoma by Transcriptional Activation of SNAI2

“…Recent studies demonstrated that upregulated FOXD1 was related to the metastasis status and adverse clinical outcomes of oral squamous cell carcinoma [10]. Besides, FOXD1-AS1 could enhance the proliferation and decrease the apoptosis of nasopharyngeal carcinoma by upregulating FOXD1 expression [21]. These results indicate that FOXD1 can behave as an oncogene in cancer.…”

LncRNA PCAT18 Promotes Non-Small Cell Lung Cancer Progression by Sponging miR-4319

“…In recent years, accumulating evidence has revealed fundamental roles of lncRNAs in the regulation of numerous physiological and pathological processes, such as cell differentiation, proliferation and apoptosis, and the initiation and progression of human cancer. 7 , 15 , 16 At present, it is widely acknowledged that numerous lncRNAs are involved the progression of NSCLC. For example, long noncoding RNA KCNMB2-AS1 increased ROCK1 expression by Sponging microRNA-374a-3p to facilitate the progression of NSCLC.…”

“…5,6 Emerging researches have suggested that lncRNAs serve crucial functions in the initiation and development of human cancer. 7,8 Numerous studies have demonstrated that lncRNAs were involved in NSCLC progression. 9,10 LncRNA PCAT18 was a recently identified lncRNA.…”