miR-196b-5p–mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer
| Autor: | Xiangjie Huang, Ri Cui, Matteo Fassan, Sisi Xiao, Canwei Wang, Chengguang Zhao, Yun Yu, Carlo M. Croce, Wei Meng, Changtian Yin, Xiaokun Li, Yumin Wang, Guang Liang, Peng Zou, Masahisa Kudo, Wangyu Zhu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Lung Neoplasms
Tetraspanins Down-Regulation Mice Nude Biology NSCLC law.invention Mice GATA6 TSPAN12 Downregulation and upregulation law Carcinoma Non-Small-Cell Lung Cell Line Tumor GATA6 Transcription Factor microRNA medicine Animals Humans Lung cancer Cell Proliferation QKI Multidisciplinary miR-196b Cell cycle Biological Sciences medicine.disease Xenograft Model Antitumor Assays respiratory tract diseases Gene Expression Regulation Neoplastic MicroRNAs Tumor progression Cancer research Disease Progression Suppressor Female |
| Zdroj: | Proc Natl Acad Sci U S A |
| Popis: | Lung cancer is the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases. The RNA binding protein, QKI, belongs to the STAR family and plays tumor-suppressive functions in NSCLC. QKI-5 is a major isoform of QKIs and is predominantly expressed in NSCLC. However, the underlying mechanisms of QKI-5 in NSCLC progression remain unclear. We found that QKI-5 regulated microRNA (miRNA), miR-196b-5p, and its expression was significantly up-regulated in NSCLC tissues. Up-regulated miR-196b-5p promotes lung cancer cell migration, proliferation, and cell cycle through directly targeting the tumor suppressors, GATA6 and TSPAN12. Both GATA6 and TSPAN12 expressions were down-regulated in NSCLC patient tissue samples and were negatively correlated with miR-196b-5p expression. Mouse xenograft models demonstrated that miR-196b-5p functions as a potent onco-miRNA, whereas TSPAN12 functions as a tumor suppressor in NSCLC in vivo. QKI-5 bound to miR-196b-5p and influenced its stability, resulting in up-regulated miR-196b-5p expression in NSCLC. Further analysis showed that hypomethylation in the promoter region enhanced miR-196b-5p expression in NSCLC. Our findings indicate that QKI-5 may exhibit novel anticancer mechanisms by regulating miRNA in NSCLC, and targeting the QKI5∼miR-196b-5p∼GATA6/TSPAN12 pathway may enable effectively treating some NSCLCs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|