M2 Macrophages Promote HCC Cells Invasion and Migration via miR-149-5p/MMP9 Signaling

M2 Macrophages Promote HCC Cells Invasion and Migration via miR-149-5p/MMP9 Signaling
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M2 巨噬细胞通过 miR-149-5p/MMP9 信号传导促进 HCC 细胞侵袭和迁移。

DOI:
10.7150/jca.35444
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发表时间:
2020-01-01
期刊:
影响因子:
3.9
通讯作者:
Li, Yixiong
Li, Yixiong
中科院分区:
医学3区
文献类型:
--
作者:
Liu, Guodong;Yin, Lei;Li, Yixiong

文献摘要

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M2巨噬细胞在胰腺癌、肾癌等多种肿瘤中促进肿瘤进展和化疗耐药的作用已得到充分研究,但其与肝癌细胞的关系尚不清楚。我们发现M2巨噬细胞可以通过改变miR-149- 5 p来增加HCC细胞中MMP 9的表达,并且机制分析显示miR-149- 5 p可能直接靶向MMP 9-mRNA的3 'UTR来抑制其翻译。具有oemiR-149- 5 p的体内原位异种移植物小鼠模型也验证了体外数据。总之,这些发现表明M2巨噬细胞可能通过改变miR-149- 5 p来促进HCC进展,靶向M2巨噬细胞/miR-149 - 5 P/MMP 9信号传导可能有助于开发新的治疗方法,以更好地抑制HCC进展。
The roles of M2 macrophages on promoting tumor progression and chemotherapy resistance have been well studied in many cancers, such as pancreatic cancer, kidney cancer and so on, but its linkage to HCC cells still remains unclear. Here we found that M2 macrophages could alter miR-149-5p to increase MMP9 expression in HCC cells and mechanism dissection revealed that miR-149-5p might directly target the 3'UTR of MMP9-mRNA to suppress its translation. The in vivo orthotopic xenografts mouse model with oemiR-149-5p also validated in vitro data. Together, these findings suggest that M2 macrophages may through altering the miR-149-5p to promote HCC progression and targeting the M2 macrophages/miR149-5P/MMP9 signaling may help in the development of the novel therapies to better suppress the HCC progression.