MiR-198 affects the proliferation and apoptosis of colorectal cancer through regulation of ADAM28/JAK-STAT signaling pathway

L.-X. Li, I.-H. Lam, F.-F. Liang, S.-P. Yi, L.-F. Ye, J.-T. Wang, W.-W. Guo, M. Xu

Department of Gastroenterology, Guangdong Second Provincial General Hospital, Guangzhou, China. lixuan_li@yeah.net

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• Oncology

OBJECTIVE: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. microRNA-198 (miR-198) was reported to be a tumor suppressive miRNA but its role in CRC is largely unknown. Thus, we aimed to investigate the role of miR-198 and its downstream signaling pathway in CRC.

PATIENTS AND METHODS: Quantitative Real-time PCR was conducted to measure miR-198 expression in human CRC cell lines (SW620, SW480 and HT29) and normal colon cell line (FHC). Using MTT, colony formation and flow cytometry assay, we investigated the effects of miR-198 on cell proliferation, colony formation and apoptosis. Luciferase activity reporter assay and Western blot assay were performed to validate the target of miR-198. Using Western blot assay, we detected the protein levels of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway.

RESULTS: The results showed that miR-198 expression was significantly reduced in CRC cell lines compared with FHC. Overexpression of miR-198 inhibits CRC cell proliferation and colony formation but promotes apoptosis. Further study revealed ADAM metallopeptidase domain 28 (ADAM28) was a direct target of miR-198, and the overexpression of ADAM28 reversed the effects of miR-198 on cell behaviors. Besides that, miR-198 blocks the JAK/STAT pathway through regulating ADAM28.

CONCLUSIONS: These results collectively revealed miR-198 inhibited cell proliferation but promoted apoptosis through targeting ADAM28 and blocking JAK/STAT pathway in CRC cells.

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