In parallel, NR4A1 also regulated expression of β1-integrin, which with PAX3-FOXO1A, contributed to tumor cell migration that was blocked by C-DIM/NR4A1 antagonists.
These results demonstrate that NR4A1 is downregulated in TNBC and restoration of NR4A1 expression inhibits TNBC growth and metastasis, suggesting that NR4A1 is a tumor suppressor in TNBC.
In addition to extend our previous findings that tumor growth was inhibited in Nur77 knockout mice, we found that metastasis of colorectal tumor was completely inhibited in Nur77-/- mice.
Collectively, our study demonstrated that Nur77 could promote the invasion and metastasis of CRC cells through regulation of MMP-9/E-cadherin signaling.
Accordingly, restoring NR4A1 expression ameliorated the effects of NR4A1AS knockdown on tumor growth and metastasis of CRC cells <i>in vitro</i> and <i>in vivo</i> Thus, we conclude that NR4A1AS up-regulates NR4A1 expression by forming RNA-RNA complexes and blocking UPF1-mediated mRNA destabilization, and it functions in tumor growth and metastasis of CRC cells at least partly through regulating NR4A1, suggesting that NR4A1AS might be as a potential target for RNA-based anti-CRC drug studies.