Title:The Mediating Role of miR-451/ETV4/MMP13 Signaling Axis on Epithelialmesenchymal
Transition in Promoting Non-small Cell Lung Cancer Progression
Volume: 17
Author(s): Xue-Jiao Qian, Jing-Wen Wang, Jiang-Bo Liu and Xi Yu*
Affiliation:
- Department of Respiratory and Critical Care, Tianjin First Central Hospital, Tianjin 300192, China
Keywords:
ETV4, Lung cancer, miR-451, MMP13, Non-small cell lung cancer, TNM stage I–III.
Abstract:
Background:
Lung cancer is a leading cause of cancer mortality. It is one of the most abundant cancer types clinically, with 2 million new cases diagnosed
yearly.
Aims:
Using clinically collected non-small cell lung cancer (NSCLC) samples, we sought to hypothesize an innovative intact signaling cascade for the
disorder.
Methods:
We dissected snap-frozen NSCLC tissues along with sibling-paired nearby non-tumorous tissues from 108 NSCLC patients. We measured the
expression levels of miR-451/ETV4/MMP13 using qRT-PCR and did a thorough investigation of the molecular mechanism for the signaling axis
in NSCLC cell line A549. We also studied the epithelial-mesenchymal transition (EMT) process.
Results:
The activity of miR-451 was significantly decreased in NSCLC tissues, while the expression levels of ETV4 and MMP13 were remarkably
increased. At the same time, miR-451 levels maintained a declining trend across TNM stage I–III. Inversely, ETV4 and MMP13 increased as the
TNM stage increased. The miR-451/ETV4/MMP13 signaling axis was closely associated with prognosis in NSCLC patients. Based on in vitro
experiments, ETV4 was a direct targeting factor for miRNA-451. Meanwhile, ETV4 promoted the tumor properties of NSCLC cells by directly
activating MMP13. Silencing MMP13 blocked the EMT progress of NSCLC cells.
Conclusion:
Overall, we hypothesized an impeccable signaling pathway for NSCLC from a new aspect, and this can offer alternative insights for a better
understanding of the disorder.
