MicroRNA-138 acts as a tumor suppressor in non small cell lung cancer via targeting YAP1
Ling Xiao1,2,3, Hui Zhou4, Xiang-Ping Li1,2
1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan 410078, P.R. China.
Abstract:
MicroRNA (miR)-138 was found to have suppressive effects on the growth and metastasis of different human cancers. In this study, we aimed to investigate the regulatory mechanism of miR-138 in non-small cell lung cancer (NSCLC). We applied the Quantitative real-time PCR (qRT-PCR) to detect the miR-138 levels in NSCLC tissues (n=21) and cell lines, Bioinformatical predication, luciferase reporter assay and western blot to identify the target gene of miR-138. We also applied Cell transfection, MTT, transwell, and wound healing assays to reveal the role of miR-138 in NSCLC cell proliferation and malignant transformation. We observed that miR-138 expression level was significantly decreased in NSCLC tissues compared to their matched adjacent normal tissues. It was also downregulated in tissues with poor differentiation, advanced stage or lymph nodes metastasis, as well as in several NSCLC cell lines compared to normal lung epithelial cell. We further identified YAP1 as a direct target gene of miR-138, and observed that the protein level of YAP1 was negatively mediated by miR-138 in NSCLC A549 cells. Moreover, overexpression of miR-138 significantly inhibited A549 cell growth, invasion and migration, while knockdown of miR-138 enhanced such capacities. Further investigation showed that the cell proliferation capacity was higher in the miR-138+YAP1 group, when compared with that in the miR-138 group, suggesting that overexpression of YAP1 rescued the suppressive effects of miR-138 upregulation on NSCLC cell proliferation. However, we found no difference of cell invasion and migration capacities between miR-138+YAP1 group and miR-138 group. Finally, YAP1 was markedly upregulated in NSCLC tissues compared to their marched adjacent normal tissues. Its mRNA levels were reversely correlated with the miR-138 levels in NSCLC tissues. In summary, our study suggests that miR-138 may play a suppressive role in the growth and metastasis of NSCLC cells partly at least by targeting YAP1.
Insights
MicroRNA-138 (miR-138) suppresses non-small cell lung cancer (NSCLC) growth and metastasis by targeting YAP1. Lower miR-138 levels correlate with advanced NSCLC, and restoring miR-138 inhibits cancer cell proliferation and invasion.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNA-138 (miR-138) exhibits tumor-suppressive properties in various human cancers.
- The specific role and regulatory mechanisms of miR-138 in non-small cell lung cancer (NSCLC) require further elucidation.
Purpose of the Study:
- To investigate the regulatory mechanism of miR-138 in NSCLC.
- To identify the direct target gene of miR-138 and its role in NSCLC progression.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) for miR-138 expression analysis.
- Bioinformatic prediction, luciferase reporter assays, and Western blot to identify and validate miR-138 targets.
- Cell transfection, MTT, Transwell, and wound healing assays to assess cell proliferation, invasion, and migration.
Main Results:
- miR-138 was significantly downregulated in NSCLC tissues and cell lines, correlating with poor differentiation, advanced stage, and lymph node metastasis.
- YAP1 was identified as a direct target of miR-138, with its protein levels negatively regulated by miR-138 in NSCLC cells.
- Overexpression of miR-138 inhibited NSCLC cell growth, invasion, and migration, while YAP1 overexpression partially rescued the suppressive effect on proliferation.
- YAP1 was upregulated in NSCLC tissues and inversely correlated with miR-138 levels.
Conclusions:
- miR-138 plays a suppressive role in NSCLC growth and metastasis, at least partly through targeting YAP1.
- The miR-138/YAP1 axis represents a potential therapeutic target for NSCLC treatment.
Related Concept Videos
MicroRNAs
MicroRNAs
MicroRNAs
lncRNA - Long Non-coding RNAs
Abnormal Proliferation
mTOR Signaling and Cancer Progression
The mTOR pathway or the...


