LncNAP1L6 activates MMP pathway by stabilizing the m6A-modified NAP1L2 to promote malignant progression in prostate cancer
Yuxiao Zheng, Feng Qi, Lu Li, Bin Yu, Yifei Cheng, Minghui Ge, Chao Qin, Xiao Li
Abstract
Malignant progression such as bone metastasis, which is associated with pathologic fractures, pain and reduced survival frequently occurs in prostate cancer (PCa) patients at advanced stages. Accumulating evidence has supported that long non-coding RNAs (lncRNAs) participate in multiple biological processes. Nevertheless, the functions of most lncRNAs in PCa malignant progression remain largely unclear. Our current study is to elucidate the influence of lncRNA lncNAP1L6 on PCa malignant progression and uncover the possible regulatory mechanism. Firstly, RT-qPCR analysis was to detect lncNAP1L6 expression and suggested that lncNAP1L6 was markedly upregulated in PCa cells. Functional assays manifested that silencing of lncNAP1L6 hampered cell migration, invasion, and epithelial-mesenchymal transition (EMT) while overexpression of lncNAP1L6 exacerbated cell migration, invasion and EMT. In addition, mechanism assays were to determine the latent regulatory mechanism of lncNAP1L6. It turned out that METTL14/METTL3 complex mediated m6A methylation of NAP1L2 mRNA. Besides, lncNAP1L6 recruited HNRNPC to m6A-modified NAP1L2, leading to stabilization of NAP1L2 mRNA. Moreover, NAP1L6 interacted with YY1 to promote the transcription of MMP2 and MMP9 and activate MMP signaling pathway. In summary, lncNAP1L6 was identified as an oncogene in PCa, which revealed that lncNAP1L6 might be used as potential therapeutic target in PCa.