microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma.
microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma.
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microRNA-26a 通过 PI3K/Akt 通路下调巨噬细胞集落刺激因子表达，从而抑制肝细胞癌中巨噬细胞的募集
DOI：
10.1186/s13045-015-0150-4
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发表时间：
2015-05-29
影响因子：
28.5
通讯作者：
Sun HC
中科院分区：
文献类型：
--
作者：
Chai ZT;Zhu XD;Ao JY;Wang WQ;Gao DM;Kong J;Zhang N;Zhang YY;Ye BG;Ma DN;Cai H;Sun HC
研究背景microRNAs(MiRNAs)对巨噬细胞集落刺激因子(M-CSF)和巨噬细胞的调节作用已有报道。本研究的目的是探讨miR-26a能否抑制M-CSF的表达和巨噬细胞的募集。用酶联免疫吸附试验检测肿瘤细胞M-CSF的表达，用细胞迁移实验探讨肝癌细胞系对巨噬细胞体外募集的影响。实时定量聚合酶链式反应检测了巨噬细胞表达的一组mRNAs。采用异种移植模型观察肿瘤生长情况。应用免疫组织化学方法研究miR-26a的表达与M-CSF表达及巨噬细胞募集的关系。与亲代细胞相比，高表达miR-26a的HepG2细胞的条件培养液(CM)降低了佛波酯(PMA)刺激的THP-1细胞的迁移能力，增加了IL-12b或IL-23mRNA的表达，降低了趋化因子(C-C基序)配体(CCL)22、CCL17和IL-10mRNA的表达。这些作用可被PI3K/Akt途径抑制剂LY294002阻断。MiR-26a在肝癌细胞中的异位表达抑制了肿瘤的生长，抑制了M-CSF的表达，并抑制了肿瘤中巨噬细胞的浸润。在使用HCCLM3细胞时也发现了类似的结果。此外，miR-26a的表达与肝癌患者肿瘤组织中M-CSF的表达和巨噬细胞的浸润呈负相关。结论miR-26a的表达降低了肝癌组织中M-CSF的表达和巨噬细胞的募集。
BackgroundmicroRNAs (miRNAs) have been reported to modulate macrophage colony-stimulating factor (M-CSF) and macrophages. The aim of this study was to find whether miR-26a can suppress M-CSF expression and the recruitment of macrophages.MethodsHepatocellular carcinoma (HCC) cell lines with decreased or increased expression of miR-26a were established in a previous study. M-CSF expression by tumor cells was measured by enzyme-linked immunosorbent assay, and cell migration assays were used to explore the effect of HCC cell lines on macrophage recruitment in vitro. Real-time PCR measured a panel of mRNAs expressed by macrophages. Xenograft models were used to observe tumor growth. Immunohistochemistry was conducted to study the relation between miR-26a expression and M-CSF expression and macrophage recruitment in patients with HCC.ResultsEctopic expression of miR-26a reduced expression of M-CSF. The conditioned medium (CM) from HepG2 cells that overexpressed miR-26a reduced the migration ability of THP-1 cells stimulated by phorbol myristate acetate (PMA) increased expression of interleukin (IL)-12b or IL-23 mRNA and decreased expression of chemokine (C-C motif) ligand (CCL)22, CCL17, and IL-10 mRNA, in comparison to the medium from the parental HepG2 cells. These effects could be interrupted by the PI3K/Akt pathway inhibitor LY294002. Ectopic expression of miR-26a in HCC cells suppressed tumor growth, M-CSF expression, and infiltration of macrophages in tumors. Similar results were also found when using HCCLM3 cells. Furthermore, the expression of miR-26a was inversely correlated with M-CSF expression and macrophage infiltration in tumor tissues from patients with HCC.ConclusionsmiR-26a expression reduced M-CSF expression and recruitment of macrophages in HCC.
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影响因子：
--
作者：
Cheng H;Clarkson PW;Gao D;Pacheco M;Wang Y;Nielsen TO
通讯作者：
Nielsen TO
影响因子：
4.2
作者：
Katamura, Yoshio;Aikata, Hiroshi;Chayama, Kazuaki
通讯作者：
Chayama, Kazuaki
DOI：
10.1056/nejmoa0901282
发表时间：
2009-10-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ji J;Shi J;Budhu A;Yu Z;Forgues M;Roessler S;Ambs S;Chen Y;Meltzer PS;Croce CM;Qin LX;Man K;Lo CM;Lee J;Ng IO;Fan J;Tang ZY;Sun HC;Wang XW
通讯作者：
Wang XW
影响因子：
2.2
作者：
Kawamura, Kyoko;Komohara, Yoshihiro;Takeya, Motohiro
通讯作者：
Takeya, Motohiro
影响因子：
5.5
作者：
Fleetwood, Andrew J.;Dinh, Hang;Hamilton, John A.
通讯作者：
Hamilton, John A.