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Telocytes promote hepatocellular carcinoma by activating the ERK signaling pathway and miR-942-3p/MMP9 axis
Cell Death Discovery ( IF 7 ) Pub Date : 2021-08-10 , DOI: 10.1038/s41420-021-00592-z
Ying Xu 1 , Hu Tian 2 , Chao Guang Luan 3 , Kai Sun 2 , Peng Jin Bao 1 , Hua Yu Zhang 4 , Nan Zhang 4
Affiliation  

In China, hepatocellular carcinoma (HCC) is considered a malignant tumor with poor prognosis, frequent metastasis, and a high relapse rate. Telocytes (TCs) participate in tumorigenic, invasive, and migratory processes by secreting functional proteins and transmitting cell-to-cell information, but their functions in HCC are still unknown. TC counts and MMP9 expression in liver cancer tissues were measured using immunohistochemistry, western blotting, and RT-PCR. Primary TCs from liver para-cancer tissues were cultured in vitro. To verify the role of TCs in HCC, a metastatic cancer animal model was established using three types of liver cancer cell lines in vivo. TCs promoted HCC cell metastasis by MMP9 expression in vitro and in vivo. Platelet-derived growth factor-alpha (PDGF-α), secreted by HCC cells, activated the Ras/ERK signaling pathway in TCs, thereby increasing MMP9 expression; Moreover, miR-942-3p suppressed MMP9 expression in TCs. Our results reveal the role of TCs in HCC and the mechanisms by which they elicit their effects, and they may serve as novel prognostic markers for HCC.



中文翻译:

特细胞通过激活ERK信号通路和miR-942-3p/MMP9轴促进肝细胞癌

在我国,肝细胞癌(HCC)被认为是预后差、转移频繁、复发率高的恶性肿瘤。特洛细胞(TC)通过分泌功能蛋白和传递细胞间信息参与致瘤、侵袭和迁移过程,但其在 HCC 中的功能仍不清楚。使用免疫组织化学、蛋白质印迹和 RT-PCR 测量肝癌组织中的 TC 计数和 MMP9 表达。体外培养来自肝癌旁组织的原代TC。为了验证TC在HCC中的作用,使用三种类型的肝癌细胞系在体内建立了转移性癌症动物模型。TCs通过体外和体内MMP9表达促进HCC细胞转移。HCC细胞分泌的血小板源性生长因子-α(PDGF-α)激活TC中的Ras/ERK信号通路,从而增加MMP9的表达;此外,miR-942-3p 抑制 TC 中 MMP9 的表达。我们的结果揭示了 TC 在 HCC 中的作用及其产生作用的机制,并且它们可能作为 HCC 的新预后标志物。

更新日期:2021-08-11
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