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Mechanical exploration identified a physical and functional association of JMJD3 with syntenin presiding over the TGF-β in Ras-activated lung cancer cells. Taken together, these findings provide new insight into the mechanisms by which JMJD3 promotes syntenin expression resulting in oncogenic Ras cooperation with TGF-β to promote EMT.Colorectal cancer (CRC) is one of the most common cancers around the world and endangers human health seriously. Liver metastasis is an important factor affecting the long-term prognosis of CRC and the spec