MiR-335 regulates the chemo-radioresistance of small cell lung cancer cells by targeting PARP-1
MiR-335 regulates the chemo-radioresistance of small cell lung cancer cells by targeting PARP-1
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MiR-335通过靶向PARP-1调节小细胞肺癌细胞的化疗放疗耐药性
DOI：
10.1016/j.gene.2016.11.031
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发表时间：
2017-02-05
期刊：
影响因子：
3.5
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Luo, Yingshan;Tong, Lihua;Zhang, Jian
研究了 miR-335 在小细胞肺癌 (SCLC) 化疗敏感性和放射敏感性调节中的作用。 gRT-PCR 检测发现，与亲本细胞相比，多重耐药 SCLC H69AR 和 H446DDP 细胞中 miR-335 显着下调。然后，我们证明了 miR-335 表达与 SCLC 细胞的化疗放射敏感性（包括细胞增殖、细胞克隆性和细胞凋亡）之间呈负相关。此外，miR-335过表达抑制体外细胞迁移和体内肿瘤生长，而抑制miR-335则促进细胞迁移和肿瘤生长。进一步研究了潜在的机制。通过生物信息学分析，聚[ADP-核糖]聚合酶 I (PARP-1) 被鉴定为 SCLC 中 miR-335 的直接靶基因，并通过荧光素酶报告基因测定进行验证。 miR-335的过表达降低了PARP-1 mRNA和蛋白的表达，NF-κB蛋白水平相应下调，从而调节SCLC的化疗放疗敏感性。综上所述，这些发现表明 miR-335 可能是 SCLC 放化疗耐药的关键调节因子，也是新的潜在治疗靶点。 (C) 2016 年由 Elsevier B.V. 出版
The role of miR-335 in the regulation of chemosensitivity and radiosensitivity of small cell lung cancer (SCLC) was investigated. miR-335 was significantly downregulated in multi-drug-resistant SCLC H69AR and H446DDP cells compared with parental cells as detected by gRT-PCR. Then, we demonstrated the negative correlation between miR-335 expression and the chemo-radiosensitivity of SCLC cells, including cell proliferation, cell clonality and cell apoptosis. In addition, miR-335 overexpression inhibited cell migration in vitro and tumor growth in vivo, whereas inhibition of miR-335 promoted cell migration and tumor growth. The underlying mechanism was further studied. Poly [ADP-ribose] polymerase I (PARP-1) was identified as a direct target gene of miR-335 in SCLC by bioinformatics analysis and validated via luciferase reporter assay. Overexpression of miR-335 decreased the expression of PARP-1 mRNA and protein, and NF-kappa B protein levels were correspondingly downregulated, thus regulating the chemo-radiosensitivity of SCLC. Taken together, these findings indicate that miR-335 may serve as a critical regulator of chemo-radiotherapy resistance in SCLC and a new potential therapeutic target. (C) 2016 Published by Elsevier B.V.