Xing Qianzhe, Xu Yanjie, Luo Ying, Li Chenglong, Wang Peng, Kang Bin, Lu Chengjun
Department of Hepatobiliary Surgery and Tianjin Institute of Hepatobiliary Disease, Third Central Hospital of Tianjin.
3Tianjin Key Laboratory of Artificial Cell, Tianjin Institute of Hepatobiliary Disease, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Third Central Hospital of Tianjin.
Eur J Histochem. 2025 Apr 7;69(2). doi: 10.4081/ejh.2025.4190. Epub 2025 May 6.
Epithelial-mesenchymal transition (EMT) is closely linked to liver cancer prognosis, invasiveness, and aggressiveness. One promising treatment for liver cancer is cell therapy, where stem cells are stimulated to develop into functional liver cells. This study aimed to investigate the effect of miR-122-5p on the differentiation of human induced pluripotent stem cells (hiPSCs) into hepatocyte-like cells and its impact on the EMT process in liver cancer cells. MiR-122-5p was overexpressed or silenced in hiPSCs to analyze the expression of liver-specific markers, including AFP, ALB and ASGPR, to confirm hepatocyte-like differentiation. A co-culture system with HepG2 liver cancer cells was also used to evaluate the effect of miR-122-5p-overexpressing hiPSCs or miR-122-5p-silencing hiPSCs on the expression of EMT markers. Results revealed that overexpression of miR-122-5p in hiPSCs induced hepatocyte-like characteristics, as evidenced by increased levels of AFP, ALB, and ASGPR. However, knockdown of miR-122-5p had the opposite effect. In the co-culture system, hiPSCs overexpressing miR-122-5p inhibited the EMT process of HepG2 cells, resulting in increased levels of mesenchymal markers and decreased levels of epithelial markers. Taken together, miR-122-5p promotes the differentiation of hiPSCs into hepatocyte-like cells and inhibits EMT process of liver cancer cells. Targeting miR-122-5p may be a novel approach to prevent liver cancer progression through cell therapy.
上皮-间质转化（EMT）与肝癌的预后、侵袭性和恶性程度密切相关。一种有前景的肝癌治疗方法是细胞疗法，即刺激干细胞发育成功能性肝细胞。本研究旨在探讨miR-122-5p对人诱导多能干细胞（hiPSC）向肝细胞样细胞分化的影响及其对肝癌细胞EMT过程的作用。在hiPSC中过表达或沉默miR-122-5p，以分析肝脏特异性标志物（包括甲胎蛋白、白蛋白和去唾液酸糖蛋白受体）的表达，从而确认肝细胞样分化。还使用了与HepG2肝癌细胞的共培养系统，以评估过表达miR-122-5p的hiPSC或沉默miR-122-5p的hiPSC对EMT标志物表达的影响。结果显示，hiPSC中miR-122-5p的过表达诱导了肝细胞样特征，甲胎蛋白、白蛋白和去唾液酸糖蛋白受体水平升高证明了这一点。然而，miR-122-5p的敲低则产生相反的效果。在共培养系统中，过表达miR-122-5p的hiPSC抑制了HepG2细胞的EMT过程，导致间充质标志物水平升高，上皮标志物水平降低。综上所述，miR-122-5p促进hiPSC向肝细胞样细胞分化，并抑制肝癌细胞的EMT过程。靶向miR-122-5p可能是一种通过细胞疗法预防肝癌进展的新方法。
