miR-198 functions as a tumor suppressor in breast cancer by targeting CUB domain-containing protein 1.

The molecular mechanisms underlying the dysregulation of microRNAs (miRs) have been previously documented in breast cancer. miR-198 has been reported to be deregulated in several human cancers. However, the detailed effects of miR-198 on breast cancer progression remain unclear. Using quantitative polymerase chain reaction analysis, we demonstrated in the present study that miR-198 was downregulated in breast cancer tissues and cell lines, and that downregulation of miR-198 was significantly correlated with lymph node metastasis. Functional studies revealed that miR-198 inhibited cell proliferation and migration and promoted cell adhesion in aggressive breast cancer cells in vitro. In addition, we observed that CUB domain-containing protein 1 (CDCP1) was a direct target of miR-198, and that knockdown of CDCP1 inhibited cell proliferation and migration, and promoted cell adhesion, which was similar to the effects of overexpression of miR-198. Taken together, we provide evidence to characterize the role of miR-198/CDCP1 interaction in breast cancer, which may be useful in breast cancer therapy.

MiR-199a-5p loss up-regulated DDR1 aggravated colorectal cancer by activating epithelial-to-mesenchymal transition related signaling.

BACKGROUND: Discoidin domain receptors1 (DDR1) is associated with tumor progression, and its dysregulated expression has been observed in many cancers. AIM: We aim to explore molecular mechanism underlying the role of DDR1 in colorectal cancer development. METHODS: Immunohistochemistry and Western blot were applied to examine the DDR1 expression. Real-time RT-PCR and Western blot were performed to determine the expression of miR-199a-5p and DDR1. Luciferase reporter assay was used to determine whether DDR1 was a target of miR-199a-5p. Effects of miR-199a-5p and DDR1 on colorectal cell proliferation, colony formation, cell cycle progression, invasion and migration were then investigated. Western blot was used to determine the relative signal pathways. RESULTS: Increased DDR1 and decreased miR-199a-5p expression coexisted in CRC, knockdown of DDR1 or overexpression of miR-199a-5p both resulted in reduced colony formation, invasive and migratory capabilities of human CRC LOVE1 and LOVO cells. It was also found that overexpression of miR-199a-5p led to decreased DDR1, MMP2, N-cadherin and vimentin expression and increased E-cadherin expression in both CRC cell lines. However, down-regulation of miR-199a-5p resulted in the opposite effects. Dual luciferase reporter assay confirmed that miR-199a-5p could directly target DDR1 through binding to its 3'-UTR. CONCLUSIONS: Our findings indicated that up-regulation of DDR1 induced by miR-199a-5p down-regulation may contribute to the development and progression of CRC, and this effect may be associated with increased invasiveness, at least in part, via activating the EMT-related signaling.