Long non-coding RNA HOXA11-AS upregulates Cyclin D2 to inhibit apoptosis and promote cell cycle progression in nephroblastoma by recruiting forkhead box P2

摘要

Long non-coding RNAs (lncRNAs) have been highlighted to play key roles in the gene regulatory network, and the dysregulation of lncRNAs has also been implicated in various malignancies. However, little is known regarding the expression of lncRNA and their functions in the progression of nephroblastoma. Thus, the present study aimed to explore the potential role of homeobox A11 (HOXA11)-AS in nephroblastoma. Microarray-based analysis was initially applied to screen the differentially expressed lncRNAs, and HOXA11-AS was selected as the candidate. The HFWT cells were performed with gain- and loss-of function test to evaluate the role of HOXA11-AS in cell cycle and apoptosis in nephroblastoma using flow cytometry and Western blots. Moreover, the relationship between HOXA11-AS and forkhead box P2 (FOXP2) was verified by Cross-linking RIP, and the direct interaction between HOXA11-AS and Cyclin D2 (CCND2) was detected using a dual luciferase reporter gene assay. Tumor formation in nude mice was used to investigate the effect of HOXA11-AS in vivo . HOXA11-AS was found to be highly expressed in the nephroblastoma. Furthermore, the silencing of HOXA11-AS promoted apoptosis and cell cycle arrest at the G1/S phase in nephroblastoma through the transcription factor FOXP2 to downregulate the expression of CCND2. Consistently, the tumor formation data in nude mice verified the results in vivo . Taken together, silencing of HOXA11-AS promotes apoptosis and inhibits the cell cycle entry in nephroblastoma by recruiting the transcription factor FOXP2 to downregulate the expression of CCND2, highlighting a promising novel direction for future nephroblastoma treatment.