Inhibition of miR-24 suppresses malignancy of human non-small cell lung cancer cells by targeting WWOX in vitro and in vivo.
Inhibition of miR-24 suppresses malignancy of human non-small cell lung cancer cells by targeting WWOX in vitro and in vivo.
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DOI：
10.1111/1759-7714.12824
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发表时间：
2018-12
期刊：
影响因子：
2.9
通讯作者：
Xie JY
中科院分区：
文献类型：
--
作者：
Wang XH;Gan CZ;Xie JY
我们研究了micro-RNA 24（miR-24）和WWOX对体外和体内非小细胞肺癌（NSCLC）细胞增殖和迁移的影响。我们通过生物信息学分析和3′非翻译区荧光素酶分析来研究miR-24的直接靶点。采用增殖、凋亡和transwell侵袭测定来评估用pcDNA 3-WWOX过表达WWOX和用miR-24小干扰RNA敲低miR-24的效果。还使用定量真实的时间PCR、蛋白质印迹和免疫组织化学来研究miR-24和c-Kit表达以及凋亡和侵袭相关蛋白。最后，我们在裸鼠中构建了肿瘤异种移植模型，以证实miR-24对体内NSCLC细胞增殖的影响。根据我们的实验数据，miR-24抑制可以通过激活caspase 3诱导凋亡，并在体外和体内抑制NSCLC细胞的活力和增殖。miR-24下调可通过下调MMP 9降低NSCLC细胞的侵袭能力。WWOX被鉴定为miR-24的功能靶标。WWOX过表达产生与拮抗miR-24相同的作用，而阻断WWOX抵消了由miR-24抑制引起的肿瘤抑制作用。miR-24可能作为癌基因发挥作用，在NSCLC的细胞生长和迁移中发挥重要作用。我们的发现增强了对miR-24调控网络和NSCLC肿瘤发生和发展的分子机制的理解。使用miR-24抑制剂抑制miR-24对癌细胞的作用可能是一种有吸引力的NSCLC治疗策略。
We investigated the effect of micro‐RNA 24 (miR‐24) and WWOX on non‐small cell lung cancer (NSCLC) cell proliferation and migration in vitro and in vivo. We performed bioinformatics analysis and 3′ untranslated region luciferase assay to investigate the direct target of miR‐24. Proliferation, apoptosis, and transwell invasion assays were employed to evaluate the effect of WWOX overexpression with pcDNA3‐WWOX and knocking down miR‐24 with miR‐24 small interfering RNA. Quantitative real‐time PCR, Western blot, and immunohistochemistry were also used to investigate miR‐24 and c‐Kit expression, and apoptosis and invasion‐related proteins. Finally, we constructed a tumor xenograft model in nude mice to confirm the effect of miR‐24 on NSCLC cell proliferation in vivo. According to our experimental data, miR‐24 inhibition could induce apoptosis by activating caspase 3 and suppress the viability and proliferation of NSCLC cells in vitro and in vivo. MiR‐24 downregulation could reduce the invasive ability of NSCLC cells by downregulating MMP9. WWOX was identified as a functional target of miR‐24. WWOX overexpression generated the same effect with antagonizing miR‐24, while blocking WWOX counteracted the tumor suppressive effect caused by miR‐24 inhibition. MiR‐24 may function as an oncogene and play an important role in the cell growth and migration of NSCLC. Our findings enhance understanding of the miR‐24 regulatory network and the molecular mechanism that underlies the oncogenesis and development of NSCLC. Suppressing the effect of miR‐24 on cancer cells using a miR‐24 inhibitor may be an attractive therapeutic strategy against NSCLC.
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