The results provided further evidence for the putative role of the RB1 gene alterations in the metastatic process, although a contribution by other gene(s) during metastasiscannot beruled out.
Additionally, resveratrol treatment inhibited SG-mediated Rbfox2 localization, further inhibiting RB1 protein expression, and inhibited specific Rbfox2 localization to the cytoplasm in melanoma B16-F10 cells, thereby effectively inhibiting metastasis and tumor growth ability.
Instead, we identified deletion of the p16 (CDKN2A) and retinoblastoma (RB1) genes as likely causal events leading to increased AURKA and CINSARC gene expression, to chromosome rearrangement, and ultimately to metastasis.
Forest plots resulting from our meta-analyses illustrate that loss of RB1 function results in a 1.62-fold increase in the mortality rate for osteosarcoma patients (RR = 1.62, 95% CI: 1.23-2.13; Z = 3.44, P = 0.0006), a significant increase in osteosarcoma metastasis (OR = 3.95, 95% CI: 1.86-8.38; Z = 3.57; P = 0.0004), and a significant reduction in the histological response of osteosarcoma to chemotherapy (OR = 0.35; 95% CI: 0.13-0.94; Z = -2.08; P = 0.038).
Interestingly, ectopic expression of miR-200b in the Caki-1 and OSRC-2 cell lines suppresses cell migration and invasion in vitro as well as tumor metastases in vivo.