Cancer Res Treat.  2019 Oct;51(4):1420-1429. 10.4143/crt.2018.638.

MiR-1246 Promotes Metastasis and Invasion of A549 cells by Targeting GSK-3β‒Mediated Wnt/β-Catenin Pathway

Affiliations
  • 1The Second People's Hospital of China Three Gorges University, Yichang, China.
  • 2Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Yichang, China. zyjzyq@163.com
  • 3Medical College of Three Gorges University, Yichang, China.
  • 4The Institute of Infection and Inflammation, China Three Gorges University, Yichang, China.

Abstract

PURPOSE
MicroRNAs (miRNAs) are a group of small non-coding RNAs involved in different cancers, including lung cancer. Here, we aim to investigate the expression profiles of circulating miRNAs and their roles contributed to the progress of lung cancer.
MATERIALS AND METHODS
The levels of circulating miRNA in lung cancer patients were investigated by miRNAs assay. Then we predicted the target genes of aberrantly expressing miRNAs by searching genetic databases. Based on the A549 cells transfected with miR-1246 mimics or miR-1246 inhibitor,we further measured the roles of miR-1246 involving in the epithelial-mesenchymal transition (EMT), migration and invasion capacities of lung cancer cells in vitro. Finally, we detected the effects of miR-1246 on glycogen synthase kinase-3β (GSK-3β)/β-catenin pathway by immunofluorescence and Western blot, respectively.
RESULTS
We identified that 14 miRNAs were aberrantly expressed in the serum of lung cancer patients. Among them, miR-1246 was the most up-regulated. The cell assays indicated that miR-1246 significantly increased the migration and invasion capabilities of A549 lung cancer cells. Meanwhile, immunofluorescence analysis revealed that miR-1246 promoted EMT process of A549 cells accompanying with decreasing E-cadherin expression, while increasing vimentin and transforming growth factor β (TGF-β) expression. Furthermore, an online tool predicated that miR-1246 might bind to 3"²-untranslated region of GSK-3β, which was confirmed by overexpression and knockdown of miR-1246 assays.
CONCLUSION
Taken together, the study illustrates that miR-1246 regulates Wnt/β-catenin pathway through targeting GSK-3β/β-catenin, which partly contributing to tumor metastasis. MiR-1246 may play an essential role in the diagnosis and therapeutic of lung cancer.

Keyword

MiR-1246; Epithelial–mesenchymal transition; Metastasis; Glycogen synthase kinase 3β; β-catenin; Lung neoplasms

MeSH Terms

Blotting, Western
Cadherins
Databases, Genetic
Diagnosis
Epithelial-Mesenchymal Transition
Fluorescent Antibody Technique
Glycogen Synthase
Humans
In Vitro Techniques
Lung Neoplasms
MicroRNAs
Neoplasm Metastasis*
RNA, Small Untranslated
Transforming Growth Factors
Vimentin
Cadherins
Glycogen Synthase
MicroRNAs
RNA, Small Untranslated
Transforming Growth Factors
Vimentin
Full Text Links
  • CRT
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
    DB Error: unknown error