■癌症相关的间充质干细胞(MSC)通过外泌体递送的成分调节癌症的进展,虽然很少有研究进行肝细胞癌(HCC)。本研究旨在评估来自HCC相关MSCs(HCC-MSCs)的外泌体对HCC细胞功能的影响以及潜在的调节机制。
■HCC细胞(Huh7和PLC)正常培养或与HCC-MSCs共培养,HCC-MSC加GW4869或HCC-MSC衍生的外泌体;然后进行mRNA测序和RT-qPCR验证。随后,在HCC细胞中筛选和修饰候选基因。接下来,TMBIM6修饰的HCC-MSC用于治疗HCC细胞。
■HCC-MSCs及其来源的外泌体均促进增殖,入侵,球体形成能力,但抑制肝癌细胞凋亡(均p<0.05);然而,外泌体抑制剂(GW4869)抑制了HCC-MSCs对这些细胞功能的影响。随后,通过mRNA测序和RT-qPCR验证,将TMBIM6,EEF2和PRDX1分选为与HCC-MSC衍生的外泌体调节HCC细胞功能有关的候选基因。其中,TMBIM6具有有效的作用(所有p<0.05),而EEF2和PRDX1对调节HCC细胞活力和侵袭能力的影响较小。接下来,直接沉默TMBIM6抑制了生存能力,球体形成,入侵,上皮-间质转化(EMT),和PI3K/AKT通路,但促进肝癌细胞凋亡;然而,过表达TMBIM6显示出相反的效果。此外,与来自TMBIM6修饰的HCC-MSC的外泌体一起孵育在HCC细胞中呈现与直接TMBIM6修饰类似的效果。
■HCC-MSC衍生的外泌体通过PI3K/AKT途径传递TMBIM6以促进HCC的恶性行为。
UNASSIGNED: Cancer-associated mesenchymal stem cells (MSCs) regulate the progression of cancers through exosome-delivered components, while few studies are conducted on hepatocellular carcinoma (HCC). This study aimed to evaluate the effect of exosomes from HCC-associated MSCs (HCC-MSCs) on HCC cellular functions and the potential regulatory mechanism.
UNASSIGNED: HCC cells (Huh7 and PLC) were cultured normally or co-cultured with HCC-MSCs, HCC-MSCs plus GW4869, or HCC-MSC-derived exosomes; then mRNA sequencing and RT-qPCR validation were conducted. Subsequently, candidate genes were sorted out and modified in HCC cells. Next,
TMBIM6-modified HCC-MSCs were used to treat HCC cells.
UNASSIGNED: Both HCC-MSCs and their derived exosomes promoted proliferation, invasion, sphere formation ability but suppressed apoptosis in HCC cells (all p < 0.05); however, the effect of HCC-MSCs on these cellular functions was repressed by exosome inhibitor (GW4869). Subsequently, TMBIM6, EEF2, and PRDX1 were sorted out by mRNA sequencing and RT-qPCR validation as candidate genes implicated in the regulation of HCC cellular functions by HCC-MSC-derived exosomes. Among them, TMBIM6 had a potent effect (all p < 0.05), while EEF2 and PRDX1 had less effect on regulating HCC cell viability and invasion. Next, direct silencing
TMBIM6 repressed viability, sphere formation, invasion, epithelial-mesenchymal transition (EMT), and PI3K/AKT pathway but promoted apoptosis in HCC cells; however, overexpressing TMBIM6 showed the opposite effect. Furthermore, incubating with exosomes from
TMBIM6-modified HCC-MSCs presented a similar effect as direct
TMBIM6 modification in HCC cells.
UNASSIGNED: HCC-MSC-derived exosomes transmit
TMBIM6 to promote malignant behavior via PI3K/AKT pathway in HCC.