骨形态发生蛋白 9 对肝细胞癌肿瘤干细胞 干性、增殖和侵袭的影响及机制.

Objective To explore the effects and mechanism of bone morphogenetic protein 9(BMP9) on the stem‐ ness, proliferation and invasion of cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Methods Normal liv‐ er cells, liver carcinoma cells, and liver carcinoma tumor stem cells in the logarithmic growth phase were selected. RT-qP‐ CR was used to detect BMP9 mRNA expression. Western blotting was used to detect BMP9 protein expression. HepG2- CSCs were transfected with lentiviral interference vectors to knock down BMP9 expression, which were then divided into HepG2-CSCs group and HepG2-CSCs-BMP9 knockdown group. After adding MAPK/ERK signal agonists (DIPQUO), cells were divided into three groups, HepG2-CSCs group, HepG2-CSCs knockdown group, and HepG2-CSCs knockdown+ DIPQUO group. RT-qPCR was used to detect the expression levels of stemness-related molecules CD44, SOX2, and OCT4 in HepG2-CSCs. CCK-8 assay was used to detect cell proliferation ability. Transwell assay was used to detect cell in‐ vasion ability. Western blotting was used to detect the expression of key proteins in the MAPK/ERK pathway. Results Compared with normal liver cells, BMP9 expression was up-regulated in liver carcinoma cells and HepG2-CSCs (P< 0. 05). The BMP9 mRNA and protein expression levels in HepG2-CSCs were higher than those in HepG2 cells (both P< 0. 05). After BMP9 knockdown, the mRNA expression levels of stem cell-related markers CD44, SOX2, and OCT4 in HepG2 CSCs in the HepG2-CSCs-BMP9 knockdown group were lower than those in the HepG2-CSCs group (all P<0. 05). Compared with the HepG2-CSCs group, BMP9 knockdown inhibited the cell proliferation ability of HepG2-CSCs in the HepG2-CSCs-BMP9 knockdown group at 48, 72, and 96 h (all P<0. 05), and inhibited the migration and invasion abili‐ ties of HepG2-CSCs cells (all P<0. 05). Compared with the HepG2-CSCs group, after BMP9 knockdown, the expression levels of p-ERK1/2 and p-MEK1/2 proteins in the HepG2-CSCs-BMP9 knockdown group significantly decreased (all P< 0. 05). After adding DIPQUO, the expression levels of stem cell-related markers CD44, SOX2, and OCT4 mRNA increased in the HepG2-CSCs knockdown+DIPQUO group (all P<0. 05), and the proliferation and invasion abilities of HepG2-CSCs were enhanced (all P<0. 05). Conclusion Knockdown of BMP9 can inhibit the dry maintenance and pro‐ liferation and invasion functions of HepG2 CSCs, and the mechanism may be related to the inhibition of the MAPK/ERK pathway. [ABSTRACT FROM AUTHOR]