Long non-coding RNA NAP1L6 promotes tumor progression and predicts poor prognosis in prostate cancer by targeting Inhibin-β A.

Background/purpose: Long non-coding RNAs (lncRNAs) have emerged as key molecules in initiation and progression of prostate cancer (PCa). In this study, we aimed to explore the role of lncRNA NAP1L6 in the development and progression of PCa.

Materials and methods: We identified that lncRNA NAP1L6 was over-expressed both in PCa tissues and cell lines by gene expression array profiling. The expression level of NAP1L6 in 75 PCa tissues and adjacent tissues was detected by RT-PCR. Next, the correlations between NAP1L6 expression and clinical features of patients with PCa were analyzed by paired t -test or chi-squared test, and its association with patient prognosis was assessed by the Kaplan-Meier method. The effects of NAP1L6 on PC-3 and 22RV1 cells were evaluated by Cell Counting Kit-8 (CCK-8), migration, invasion, and colony formation assays. Further analysis of the results of the microarray was performed to find downstream gene of NAP1L6. Cell function experiments were performed in order to explore the relationship between NAP1L6 and Inhibin-β A (INHBA) and the specific mechanism by which INHBA affects the development of PCa.

Results: Using microarray analysis, we identified 412 lncRNAs and 1245 mRNAs to be significantly differentially expressed in three PCa samples when compared with adjacent non-tumor tissues (ANTT) (fold-change ≥2.0 or ≤0.5, P <0.05, false discovery rate (FDR) <0.05). NAP1L6 expression was upregulated in PCa tissues and cell lines (both P <0.05) compared with ANTT. Besides, high expression level of NAP1L6 promotes PCa cell proliferation, migration, and invasion (all P <0.05), and is significantly associated with larger tumor diameter, distant metastasis, and shorter survival time (all P <0.05). We found that NAP1L6 promoted the expression of INHBA ( P <0.05), and knockdown of NAP1L6 led to the reduction of PCa cell migration, invasion, and proliferation by regulating the expression of INHBA (all P <0.05).

Conclusion: lncRNA NR6A1 might play an oncogenic role in PCa initiation and progression by regulating the expression of INHBA, and might act as a novel prognostic biomarker for PCa treatment.