Purpose: At present, there are few studies on the mechanisms underlying postoperative recurrence of liver cancer, and the mechanism of action of miR-602  in postoperative recurrence of liver tumors is not clear. Our goals were to investigate the effects of miR-602  on the expression of the Ras-associated domain family 1A (RASSF1A ) gene and the regulation of primary and recurrent hepatic tumors to clarify the molecular mechanisms of miR-602  in postoperative hepatocellular carcinoma.
Methods: We constructed a mouse liver orthotopic tumor model and a mouse liver recurrent tumor model. We measured the expression levels of the RASSF1A  gene and then analyzed the effects of miR-602  on the regulation of RASSF1A . We transiently transfected the miR-602  gene into cells that stably overexpressed RASSF1A  and examined relevant indicators to elucidate the mechanisms by which miR-602  regulates the RASSF1A/c-Jun N-terminal kinase (JNK) pathway in recurrence and dormancy in liver cancer.
Results: RASSF1A  expression was inversely related to that of JNK , activating transcription factor 2 (ATF-2 ), and c-Jun  in SMMC7721 cells stably transfected with the RASSF1A  gene and in recurrent mouse tumor tissues. After transient transfection of cells with miR-602  mimic or miR-602  inhibitor, the expression of miR-602  was inversely related to that of RASSF1A .
Conclusion: MiR-602  might inhibit the JNK signaling pathway by inhibiting the expression of RASSF1A , thereby promoting recurrence of liver cancer after surgery. The low expression levels of miR-602  in liver cancer tissues were closely related to postoperative recurrence; they could be used as a marker to judge the prognosis of patients with liver cancer.
Keywords: miR-602 , JNK, RASSF1A, liver cancer, postoperative recurrence