MicroRNA-3666 inhibits lung cancer cell proliferation, migration, and invasiveness by targeting BPTF.

Abstract

A previous study by our group indicted that overexpression of bromodomain PHD-finger transcription factor (BPTF) occurs in lung adenocarcinoma, and is closely associated with advanced clinical stage, higher numbers of metastatic lymph nodes, the occurrence of distant metastasis, low histological grade, and poor prognosis. Down-regulation of BPTF inhibited lung adenocarcinoma cell proliferation and promoted lung adenocarcinoma cell apoptosis. The purpose of this study is to identify valuable microRNAs (miRNAs) that target BPTF to modulate lung adenocarcinoma cell proliferation. In our results, we found that miR-3666 was notably reduced in lung adenocarcinoma tissues and cell lines. Using an miR-3666 mimic, we discovered that cell proliferation, migration, and invasiveness were suppressed by miR-3666 overexpression, but these were all enhanced when the expression of miR-3666 was reduced. Moreover, bioinformatics analysis using the TargetScan database and miRanda software suggested a putative target site in BPTF 3'-UTR. Furthermore, using a luciferase reporter assay, we verified that miR-3666 directly targets the 3'-UTR of BPTF. Using Western blot we discovered that overexpression of miR-3666 negatively regulates the protein expression of BPTF. Finally, we identified that the PI3K-AKT and epilthelial-mesenchymal transition (EMT) signaling pathways were inhibited by miR-3666 overexpression in lung cancer cells. In conclusion, our data indicate that miR-3666 could play an essential role in cell proliferation, migration, and invasiveness by targeting BPTF and partly inhibiting the PI3K-AKT and EMT signaling pathways in human lung cancers.

• Authors: Linqing Pan, Zhipeng Tang, Lina Pan, Ranran Tang
• Journal: Biochemistry and cell biology = Biochimie et biologie cellulaire (Biochem Cell Biol) Vol. 97 Issue 4 Pg. 415-422 (08 2019) ISSN: 1208-6002 [Electronic] Canada
• PMID: 30481052 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Nuclear
• MIRN3666 microRNA, human
• MicroRNAs
• Nerve Tissue Proteins
• Transcription Factors
• fetal Alzheimer antigen

Topics

• Antigens, Nuclear (genetics, metabolism)
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Computational Biology
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• MicroRNAs (genetics)
• Nerve Tissue Proteins (deficiency, genetics, metabolism)
• Transcription Factors (deficiency, genetics, metabolism)
• Tumor Cells, Cultured