REST‐repressed lncRNA NPPA‐AS1 regulates cervical cancer progression by modulating miR‐302e/DKK1/Wnt/β‐catenin signaling pathway

Abstract

Long noncoding RNAs (lncRNAs), a group of transcripts, have been revealed to be critical participants in regulating multiple biological processes of malignant tumors. The knowledge of NPPA‐AS1 (a new lncRNA) in cancer research is hardly known. Thus, it is of urgent need to study the underlying role of NPPA antisense RNA 1 (NPPA‐AS1) in cervical cancer (CC). In this study, NPPA‐AS1 was discovered to be lowly expressed and upregulation of it impaired cell proliferation and migration in CC. Besides, downregulation of it led to opposite results. Molecular mechanism assays uncovered that increased expression of NPPA‐AS1 could inactivate Wnt/β‐catenin signaling pathway in CC. In addition, NPPA‐AS1 was found to negatively interact with miR‐302e whereas positively correlate with dickkopf‐1 (DKK1, an inhibitor of Wnt pathway) in CC. Besides, loss of function assay illuminated that miR‐302e inhibition restrained cell proliferation and migration in CC. Subsequent rescue assays confirmed that NPPA‐AS1 acted as a competing endogenous RNA in CC by sponging miR‐302e to upregulate DKK1 expression. Finally, the RE‐1 silencing transcription factor (REST) was testified to function as a transcription suppressor of NPPA‐AS1 in CC. In brief, REST‐repressed NPPA‐AS1 regulates CC progression by modulating miR‐302e/DKK1/Wnt/β‐catenin signaling pathway.

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“…For example, Luan et al [34] knocked down the lncRNA NPPA-AS1 in human normal cervical epithelial cells (H8 cells) and human cervical cancer cells (C33A, CaSki, HeLa, and SiHa cells) and showed that this lncRNA impaired cell proliferation and migration. Moreover, lncRNAs are known to participate in the progression of lung cancer, breast cancer, and cervical cancer [34][35][36][37]. Additionally, various lncRNAs can affect disease occurrence and outcomes through multiple molecular pathways.…”