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Updated: Dec 12, 2025
Murine Model of Metastatic Liver Tumors in the Setting of Ischemia Reperfusion Injury
Published on: August 30, 2019
miR-602 Mediates the RASSF1A/JNK Pathway, Thereby Promoting Postoperative Recurrence in Nude Mice with Liver Cancer
Cheng Zhou1,2, Yajing Huang3, Yongxu Chen1,2
1School of Medicine, South China University of Technology, Guangzhou, People's Republic of China.
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.
Insights
Low miR-602 levels promote liver cancer recurrence by inhibiting Ras-associated domain family 1A (RASSF1A) and activating the JNK pathway. This finding offers a potential prognostic marker for liver cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Postoperative recurrence of liver cancer remains a significant clinical challenge with incompletely understood mechanisms.
- The specific role of microRNA-602 (miR-602) in liver tumor recurrence and its molecular targets require further elucidation.
Purpose of the Study:
- To investigate the effect of miR-602 on the expression of the Ras-associated domain family 1A (RASSF1A) gene.
- To clarify the molecular mechanisms of miR-602 in postoperative hepatocellular carcinoma recurrence and dormancy.
Main Methods:
- Construction of mouse liver orthotopic and recurrent tumor models.
- Analysis of RASSF1A gene expression and its regulation by miR-602.
- Transient transfection of miR-602 into cells overexpressing RASSF1A to study the RASSF1A/c-Jun N-terminal kinase (JNK) pathway.
Main Results:
- RASSF1A expression was inversely correlated with JNK, activating transcription factor 2 (ATF-2), and c-Jun.
- miR-602 expression was inversely related to RASSF1A expression following transfection with miR-602 mimic or inhibitor.
Conclusions:
- miR-602 may inhibit the JNK signaling pathway by downregulating RASSF1A, thus promoting liver cancer recurrence.
- Low miR-602 expression in liver cancer tissues correlates with postoperative recurrence and may serve as a prognostic marker.
