1. miR-602 Mediates the RASSF1A/JNK Pathway, Thereby Promoting Postoperative Recurrence in Nude Mice with Liver Cancer
- Author
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Zhou, Cheng, Huang, Yajing, Chen, Yongxu, Xie, Yingjie, Wen, Huihong, Tan, Wei, and Wang, Changjun
- Subjects
liver cancer ,endocrine system ,miR-602 ,postoperative recurrence ,JNK ,RASSF1A ,OncoTargets and Therapy ,Original Research - Abstract
Cheng Zhou,1,2 Yajing Huang,3 Yongxu Chen,1,2 Yingjie Xie,4 Huihong Wen,3 Wei Tan,2 Changjun Wang1,2 1School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 2Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou, People’s Republic of China; 3Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Changjun WangGuangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, No. 106, Zhongshan Second Road, Guangzhou, People’s Republic of ChinaTel +86 20-83827812-70521Email gzwchj@126.comPurpose: 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
- Published
- 2020