Τετάρτη 18 Ιανουαρίου 2017

miR-203 Inhibits Augmented Proliferation and Metastasis of Hepatocellular Carcinoma Residual in the Promoted Regenerating Liver

Abstract

Liver resection is still the most commonly used therapeutic option for hepatocellular carcinoma (HCC) at present, and liver regeneration promotes HCC growth in the regenerating liver. The higher recurrence/metastasis of HCC is the main cause of death for HCC patients after liver resection. However, it remains unclear how to abolish the augmented growth and metastasis of the possible residual HCC induced by the promoted liver regeneration after liver resection. In this study, a rat model with liver cirrhosis and diffused HCC was established by Diethylnitrosamine administration, recombinant miR-203 adenovirus was administered to induce hepatic miR-203 overexpression and 30% partial hepatectomy (PH) was followed, then the effect of miR-203 on the proliferation, invasion and metastasis of the residual HCC in the remnant cirrhotic liver with promoted regeneration was investigated. We found that the basic spontaneous regeneration of the non-tumorous liver by 30% PH promoted proliferation, invasion and lung metastasis of the hepatic residual HCC, miR-203 overexpression further promoted the regeneration of the non-tumorous liver by up-regulating Ki67 expression and enhancing IL-6/SOCS3/STAT3 pro-proliferative signals. Importantly, miR-203 overexpression markedly inhibited the proliferation, invasion and metastasis of hepatic residual HCC through suppressing expression of Ki67, CAPNS1 and lung metastasis. Moreover, it was also found that miR-203 overexpression reversed EMT induced by hepatectomy through targeting IL-1β, Snail1 and Twist1. In conclusion, our results suggested that miR-203 overexpression inhibited the augmented proliferation and lung metastasis of the residual HCC induced by the promoted liver regeneration after PH partly by regulating EMT.

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