MNX1-AS1/PABPC1 activates Notch signaling pathway to promote progression of lung cancer

Abstract

Background MNX1-AS1 is a pan-cancer lncRNA that overexpressed in the lung cancer. However, the detail molecular mechanism by which MNX1-AS1 regulates NSCLC remains unclear.  

Aims To explore the role and mechanism of lncRNA MNX1-AS1 and its related downstream signaling pathways in the occurrence and development of NSCLC.

Methods RT-qPCR analyzed the expression of MNX1-AS1 in NSCLC tissues and cell lines.The roles of MNX1-AS1 and PABPC1 in the proliferation and invasion of NSCLC cells were assessed through CCK-8, Transwell assays. The regulated relationship between MNX1-AS1 and PABPC1 was confirmed by RNA pulldown and RIP assays. Western blot was applied to detect protein related to Notch1 signaling pathway. Xenograft tumor model was ocnstructed to verify the results in vivo.  

Results MNX1-AS1 was significantly overexpressed in NSCLC, thorough bioinformatics screening. The elevated of MNX1-AS1 enhanced the proliferation and invasion of NSCLC cells. And MNX1-AS1 interacts with PABPC1, which correlates positively with the proliferation and invasion of NSCLC cells. MNX1-AS1/PABPC1 activates the downstream Notch1 signaling pathway to promote the development of NSCLC. In vivo, MNX1-AS1 accelarates tumor growth in NSCLC model, while sh-PABPC1 or Notch signalingg pathway inhibitor (DAPT) significantly inhibited the tumorigenic ability of MNX1-AS1.

Conclusions MNX1-AS1/PABPC1 complex mediated the activation of Notch1 signaling pathway to promote the occurrence and development of NSCLC.

Keywords  MNX1-AS1; PABPC1 ; Notch signaling pathway; NSCLC