Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Int Immunopharmacol. 2020 Nov;88:106889. doi: 10.1016/j.intimp.2020.106889. Epub 2020 Aug 14.
B7-H4 and autophagy can regulate or be induced by the PI3K signaling pathway. However, the association between B7-H4 and autophagy in hepatocellular carcinoma (HCC)remains unclear. The aim of this work was to investigate whether B7-H4 regulates autophagy via the PI3K signaling pathway in HCC cells. Here, western blotting was used to measure the expression of the related proteins involved in changes in of autophagy and apoptosis, such as LC3, P62, cleaved caspase 3, cleaved PARP, BCL-2, and BAX in Huh7 and Hep3B cells. Additionally, PI3K/AKT/mTOR signaling pathway proteins were measured. Cell counting kit-8 and flow cytometry were used to analyze the effects of B7-H4 siRNA interference on cell proliferation with the interference of B7-H4 siRNA. We found that B7-H4 siRNA increased HCC cell apoptosis and autophagy, and reduced cell proliferation. Moreover, the apoptosis-related proteins cleaved caspase 3, cleaved PARP and BAX were increased and Bcl-2 was decreased after B7-H4 siRNA interference. The expression level of the autophagy-related protein LC3Ⅱ was upregulated, while expression of the autophagy adaptor P62 expression was decreased in B7-H4 siRNA-pretreated cells. Furthermore, our data revealed that B7-H4 regulated apoptosis and autophagy through the PI3K signaling pathway in HCC cells. Therefore, these results suggested that B7-H4 plays an important role in HCC progression by affecting cell apoptosis and autophagy.
B7-H4 可以与自噬相互作用或被 PI3K 信号通路所调控。然而，B7-H4 与肝癌（HCC）细胞自噬之间的关系尚不清楚。本研究旨在探讨 B7-H4 是否通过 HCC 细胞中的 PI3K 信号通路来调节自噬。在这里，我们使用 Western blot 法来测量参与自噬和凋亡变化的相关蛋白的表达，如 LC3、P62、cleaved caspase 3、cleaved PARP、BCL-2 和 BAX 在 Huh7 和 Hep3B 细胞中的表达。此外，还测量了 PI3K/AKT/mTOR 信号通路蛋白。细胞计数试剂盒-8 和流式细胞术用于分析 B7-H4 siRNA 干扰对细胞增殖的影响，同时用 B7-H4 siRNA 进行干扰。我们发现 B7-H4 siRNA 增加了 HCC 细胞凋亡和自噬，并降低了细胞增殖。此外，在 B7-H4 siRNA 干扰后，凋亡相关蛋白 cleaved caspase 3、cleaved PARP 和 BAX 增加，Bcl-2 减少。自噬相关蛋白 LC3Ⅱ的表达水平上调，而自噬接头蛋白 P62 的表达水平降低。此外，我们的数据表明，B7-H4 通过 HCC 细胞中的 PI3K 信号通路调节细胞凋亡和自噬。因此，这些结果表明，B7-H4 通过影响细胞凋亡和自噬在 HCC 进展中发挥重要作用。
