miRNA-221-3p derived from M2-polarized tumor-associated macrophage exosomes aggravates the growth and metastasis of osteosarcoma through SOCS3/JAK2/STAT3 axis.
miRNA-221-3p derived from M2-polarized tumor-associated macrophage exosomes aggravates the growth and metastasis of osteosarcoma through SOCS3/JAK2/STAT3 axis.
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DOI：
10.18632/aging.203388
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发表时间：
2021-08-13
期刊：
影响因子：
--
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Liu W;Long Q;Zhang W;Zeng D;Hu B;Liu S;Chen L
背景：M2极化的肿瘤相关巨噬细胞（TAMs）的浸润增强与骨肉瘤（OS）的转移和生长有关。在此，我们的目的是探索一种新的miR-221- 3 p穿梭M2-TAM外泌体在OS细胞的生长和转移。方法：用PMA/IL-4/IL-13诱导THP-1单核细胞来源的M2-TAMs，并与OS 143 B和Saos 2细胞共培养。进行miR-221- 3 p的过表达或下调模型以探测外泌体衍生的M2-TAM在OS细胞中的影响。采用CCK-8法、集落形成法、Transwell法和流式细胞术检测OS细胞增殖能力、集落形成、侵袭、迁移和凋亡水平。此外，通过Western blot检测OS细胞中SOCS 3/JAK 2/STAT 3轴的表达，并通过双荧光素酶报告基因检测证实了miR-221- 3 p与SOCS 3之间的联系。结果如下：OS细胞增强TAMs的M2极化，从而显著促进OS细胞的存活、集落形成、迁移和侵袭，并减少凋亡。此外，富含来自M2-极化TAM（M2-TAMs）的miR-221- 3 p的exosomes也加重OS细胞的恶性行为。然而，下调miR-221- 3 p却带来了相反的结果。此外，体内试验发现，过表达miR-221- 3 p增强了OS细胞的生长。从机制上讲，SOCS 3是miR-221- 3 p的下游靶点，miR-221- 3 p的上调会抑制SOCS 3并激活JAK 2/STAT 3。然而，JAK 2/STAT 3通路的药物干预明显抑制了OS细胞的恶性行为，miR-221- 3 p上调可显著逆转OS细胞的恶性行为。结论：来源于M2-TAMs的exosomal miR-221- 3 p通过调节SOCS 3/JAK 2/STAT 3轴促进OS进展。
Background: Enhanced infiltration of M2-polarized tumor-associated macrophages (TAMs) is linked to osteosarcoma (OS) metastasis and growth. Here, we aim to explore a novel miR-221-3p shuttled by M2-TAM exosomes in the growth and metastasis of OS cells. Methods: THP-1 monocytes-derived M2-TAMs were induced by PMA/interleukin (IL)-4/IL-13 and then co-cultured with OS 143B and Saos2 cells. Overexpression or downregulation models of miR-221-3p were conducted to probe the impacts of exosome-derived M2-TAMs in OS cells. OS cell proliferative ability, colony formation, invasion, migration and apoptotic level were measured by the cell counting kit-8 (CCK-8) assay, colony formation, Transwell assay, and flow cytometry. Moreover, the SOCS3/JAK2/STAT3 axis in OS cells was testified by western blot, and a dual-luciferase reporter assay was conducted to confirm the link between miR-221-3p and SOCS3. Results: OS cells enhanced M2 polarization of TAMs, which significantly promoted OS cells’ viability, colony formation, migration, invasion, and reduced apoptosis. Moreover, the exosomes enriched by miR-221-3p from M2-polarized TAMs (M2-TAMs) also aggravated the malignant behaviors of OS cells. However, down-regulation of miR-221-3p brought about contrary results. Further, in-vivo tests uncovered that overexpressing miR-221-3p enhanced OS cells’ growth. Mechanistically, SOCS3 was a downstream target of miR-221-3p, and up-regulation of miR-221-3p choked SOCS3 and activated JAK2/STAT3. However, the pharmacological intervention of the JAK2/STAT3 pathway obviously inhibited the malignant behaviors of OS cells, which were significantly reversed by miR-221-3p up-regulation. Conclusion: The exosomal miR-221-3p derived from M2-TAMs aggravates OS progression via modulating the SOCS3/JAK2/STAT3 axis.
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影响因子：
3.1
作者：
Wang JW;Wu XF;Gu XJ;Jiang XH
通讯作者：
Jiang XH
DOI：
10.1016/j.bbrc.2018.04.124
发表时间：
2018-09-05
影响因子：
3.1
作者：
Shi, Yong-Kang;Guo, Yu-Hua
通讯作者：
Guo, Yu-Hua
影响因子：
3.5
作者：
Santillan-Benitez, Jonnathan Guadalupe;Mendieta-Zeron, Hugo;Gonzalez-Banales, Juan Manuel
通讯作者：
Gonzalez-Banales, Juan Manuel
影响因子：
4.3
作者：
Du, Yi-xin;Guo, Lin-xin;Li, Xiang
通讯作者：
Li, Xiang
细胞间纳米层介导的microRNA转移：肝癌细胞生长的环境调节机制。
影响因子：
13.5
作者：
Kogure, Takayuki;Lin, Wen-Lang;Yan, Irene K.;Braconi, Chiara;Patel, Tushar
通讯作者：
Patel, Tushar