IL-4, a direct target of miR-340/429, is involved in radiation-induced aggressive tumor behavior in human carcinoma cells.
IL-4, a direct target of miR-340/429, is involved in radiation-induced aggressive tumor behavior in human carcinoma cells.
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DOI：
10.18632/oncotarget.13561
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发表时间：
2016-12-27
期刊：
影响因子：
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通讯作者：
Bae IH
中科院分区：
文献类型：
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作者：
Kim ES;Choi YE;Hwang SJ;Han YH;Park MJ;Bae IH
放射治疗诱导细胞因子的产生，从而增加侵袭性肿瘤行为。这种辐射效应导致放射治疗失败，并增加患者的死亡率。我们发现，白细胞介素-4（IL-4）和IL-4 R α（IL-4受体）在放射治疗后的各种人类癌细胞中高度表达。此外，与浸润性癌组织相比，IL-4在转移性癌组织中高度过表达。癌症患者中IL-4的高表达与较差的生存率密切相关。本研究的结果表明，辐射诱导的IL-4有助于肿瘤的进展和转移。放射诱导的IL-4与肿瘤的发生和转移有关。IL-4表达被miR-340和miR-429下调，其被电离辐射（IR）降低。辐射调节的miR-340/429-IL 4信号通过在体外和体内激活JAK、JNK、β-catenin和Stat 6诱导Sox 2、波形蛋白、VEGF、Ang 2和MMP-2/9的产生而增加肿瘤发生和转移。我们的研究提出了一个概念上的进步，我们的理解修改的肿瘤微环境的辐射，并表明，结合放射治疗与基因治疗，以抑制IL-4可能是一个有前途的战略，预防放射后复发和转移的患者。
Radiotherapy induces the production of cytokines, thereby increasing aggressive tumor behavior. This radiation effect results in the failure of radiotherapy and increases the mortality rate in patients. We found that interleukin-4 (IL-4) and IL-4Rα (IL-4 receptor) are highly expressed in various human cancer cells subsequent to radiation treatment. In addition, IL-4 is highly overexpressed in metastatic carcinoma tissues compared with infiltrating carcinoma tissues. High expression of IL-4 in patients with cancer is strongly correlated with poor survival. The results of this study suggest that radiation-induced IL-4 contributes to tumor progression and metastasis. Radiation-induced IL-4 was associated with tumorigenicity and metastasis. IL-4 expression was downregulated by miR-340 and miR-429, which were decreased by ionizing radiation (IR). Radiation-regulated miR-340/429-IL4 signaling increased tumorigenesis and metastasis by inducing the production of Sox2, Vimentin, VEGF, Ang2, and MMP-2/9 via activating JAK, JNK, β-catenin, and Stat6 in vitro and in vivo. Our study presents a conceptual advance in our understanding of the modification of tumor microenvironment by radiation and suggests that combining radiotherapy with genetic therapy to inhibit IL-4 may be a promising strategy for preventing post-radiation recurrence and metastasis in patients.