Reintroduction of miR-203 in bone metastatic PCa cell lines suppresses metastasis via inhibition of several critical steps of the metastatic cascade including epithelial-mesenchymal transition, invasion, and motility.
Here, we demonstrate a significant correlation between tumor thickness and loss of expression of miR-200a, miR-200c, and miR-203 in a series of 23 frozen primary melanomas, where it was confirmed in two subsequent validation series (series 1: six nevi, 15 primary melanomas, and 16 metastases; series 2: 11 matched pairs of primary melanomas and metastases).
We propose that the loss of miR-203 is a molecular link in the progression of prostate cancer metastasis and TKIs resistance characterized by high EGFR ligands output and anti-apoptotic proteins activation.
In conclusion, our results have revealed a new regulatory mechanism that involves C/EBPβ-LIP-mediated downregulation of miR-203, which plays a key role in EMT and metastasis.
From the miRNAs comprehensive regulatory network, we found that has-miR-203 regulated a large number of target genes and lncRNAs, including suppressor of cytokine signaling 3 (SOCS3) and metastasis associated in lung adenocarcinoma transcript 1 (MALAT1).
Importantly, reconstitution of Runx2 in MDA-MB-231-luc cells delivered with miR-135 and miR-203 reversed the inhibitory effect of the miRNAs on tumor growth and metastasis.
Serum miR-203 expression was significantly lower in GC patients with a higher T stage, vessel invasion, and lymph node, peritoneal, and distant metastases.
We have thus identified panels of miRNAs, which include metastasis promoting miR-200 family and miR-203, as well as oncogenic and tumor-suppressive miRNAs, that can serve as prognostic markers for MBC, and early detection markers of metastasis in BC.
Importantly, miR-203 overexpression markedly inhibited the proliferation, invasion and metastasis of hepatic residual HCC through suppressing expression of Ki67, CAPNS1 and lung metastasis.