MicroRNA-145 Inhibits Cell Migration and Invasion in Colorectal Cancer by Targeting TWIST

Autor: Zhiheng Chen, Jiayan Mao, Honggang Jiang, Kequn Chai, BoHao Lu, Xuning Shen, Yi Zhu, Wei Chen
Rok vydání: 2019
Předmět:
Zdroj: OncoTargets and Therapy. 12:10799-10809
ISSN: 1178-6930
DOI: 10.2147/ott.s216147
Popis: Introduction MicroRNAs function as oncogenes or tumor suppressors in the development of various human cancers. We investigated the effect of microRNA-145 (miR-145) on colorectal cancer (CRC) cell invasion and migration. Methods The levels of miR-145 in CRC cells were examined by quantitative PCR; Western blotting was used to detect TWIST1 (twist family bHLH transcription factor 1) protein and the epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, vimentin). Then, we transfected miR-145 mimics or inhibitor into CRC cells and used the wound healing and Transwell invasion assays to investigate their migration and invasive capability, respectively. Results The miR-145 mimics suppressed CRC cell invasion and migration significantly; in contrast, miR-145 downregulation had the opposite effect. Furthermore, miR-145 regulated TWIST1 levels negatively at transcriptional level. TWIST1 knockdown significantly inhibited the CRC cell migration ability and the number of CRC cells that crossed the Transwell membrane. There was no significant difference in terms of migration and invasive capability after the cells had been transfected with miR-145 mimics or inhibitor plus TWIST1 small interfering RNA (siRNA) as compared to the TWIST1 siRNA-only group. Furthermore, we demonstrate that the inhibition of miR-145 could enhance the capability for lung metastasis in vivo. Conclusion Taken together, these findings indicate that miR-145 acts as a new tumor suppressor by regulating TWIST1 and plays a vital role in the invasive and migration ability of CRC cells.
Databáze: OpenAIRE
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