TY  - EJOU
AU  - Li, Dandan 
AU  - He, Changjun 
AU  - Wang, Junfeng 
AU  - Wang, Yanbo 
AU  - Bu, Jianlong 
AU  - Kong, Xianglong 
AU  - Sun, Dawei 

TI  - MicroRNA-138 Inhibits Cell Growth, Invasion, and EMT of Non-Small Cell  Lung Cancer via SOX4/p53 Feedback Loop
T2  - Oncology Research

PY  - 2018
VL  - 26
IS  - 3
SN  - 1555-3906

AB  - Many studies have shown that downregulation of miR-138 occurs in a variety of cancers including non-small 
cell lung cancer (NSCLC). However, the precise mechanisms of miR-138 in NSCLC have not been well clarified. In this study, we investigated the biological functions and molecular mechanisms of miR-138 in NSCLC 
cell lines, discussing whether it could turn out to be a therapeutic biomarker of NSCLC in the future. In our 
study, we found that miR-138 is downregulated in NSCLC tissues and cell lines. Moreover, the low level of 
miR-138 was associated with increased expression of SOX4 in NSCLC tissues and cell lines. Upregulation 
of miR-138 significantly inhibited proliferation of NSCLC cells. In addition, invasion and EMT of NSCLC 
cells were suppressed by overexpression of miR-138. However, downregulation of miR-138 promoted cell 
growth and metastasis of NSCLC cells. Bioinformatics analysis predicted that SOX4 was a potential target gene of miR-138. Next, luciferase reporter assay confirmed that miR-138 could directly target SOX4. 
Consistent with the effect of miR-138, downregulation of SOX4 by siRNA inhibited proliferation, invasion, 
and EMT of NSCLC cells. Overexpression of SOX4 in NSCLC cells partially reversed the effect of miR-138 
mimic. In addition, decreased SOX4 expression could increase the level of miR-138 via upregulation of p53. 
Introduction of miR-138 dramatically inhibited growth, invasion, and EMT of NSCLC cells through a SOX4/
p53 feedback loop.
KW  - Non-small cell lung cancer (NSCLC); MicroRNA-138 (miR-138);  Sex-determining region Y (SRY)-related high-mobility group (HMG)-box 4 (SOX4);  Proliferation; Invasion; Epithelial–mesenchymal transition (EMT)

DO  - 10.3727/096504017X14973124850905