MicroRNA-29b-3p enhances radiosensitivity through modulating WISP1-mediated mitochondrial apoptosis in prostate cancer cells.
MicroRNA-29b-3p enhances radiosensitivity through modulating WISP1-mediated mitochondrial apoptosis in prostate cancer cells.
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MicroRNA-29b-3p 通过调节 WISP1 介导的前列腺癌细胞线粒体凋亡来增强放射敏感性
DOI：
10.7150/jca.48216
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发表时间：
2020
影响因子：
3.9
通讯作者：
Xia X
中科院分区：
文献类型：
--
作者：
Mao A;Tang J;Tang D;Wang F;Liao S;Yuan H;Tian C;Sun C;Si J;Zhang H;Xia X
放射治疗经常应用于临床局限性前列腺癌，但其疗效可能会因放射抗性而受到严重阻碍。 MicroRNA (miRNA) 是介导细胞对电离辐射 (IR) 反应的重要调节因子，并且与许多癌症的放射敏感性密切相关。在这项研究中，体外前列腺癌细胞系 LNCaP 证实了 miR-29b-3p 增强放射敏感性。结果表明，响应 X 射线和碳离子辐射的 IR，miR-29b-3p 表达显着上调。 miR-29b-3p 的敲低会导致放射抗性，而 miR-29b-3p 的过表达会导致放射敏感性增加（显示细胞活力降低、细胞增殖受到抑制和集落形成减少）。此外，还发现 miR-29b-3p 直接靶向 Wnt1 诱导信号蛋白 1 (WISP1)。抑制 WISP1 通过抑制 Bcl-XL 表达同时激活 caspase-3 和聚（ADP-核糖）聚合酶（PARP）来促进线粒体凋亡途径。结果表明，miR-29b-3p是一种放射增敏miRNA，可以通过靶向WISP1增强LNCaP细胞的放射敏感性。这些发现提出了一种新的治疗方法来克服前列腺癌患者的放射抗性，特别是那些 WISP1 表达水平较高的患者。
Radiotherapy is frequently applied for clinically localized prostate cancer while its efficacy could be significantly hindered by radioresistance. MicroRNAs (miRNAs) are important regulators in mediating cellular responses to ionizing radiation (IR), and strongly associate with radiosensitivity in many cancers. In this study, enhancement of radiosensitivity by miR-29b-3p was demonstrated in prostate cancer cell line LNCaP in vitro. Results showed that miR-29b-3p expression was significantly upregulated in response to IR from both X-rays and carbon ion irradiations. Knockdown of miR-29b-3p resulted in radioresistance while overexpression of miR-29b-3p led to increased radiosensitivity (showing reduced cell viability, suppressed cell proliferation and decreased colony formation). In addition, miR-29b-3p was found to directly target Wnt1-inducible-signaling protein 1 (WISP1). Inhibition of WISP1 facilitated the mitochondrial apoptosis pathway through suppressing Bcl-XL expression while activating caspase-3 and poly (ADP-ribose) polymerase (PARP). The results indicated that miR-29b-3p was a radiosensitizing miRNAs and could enhance radiosensitivity of LNCaP cells by targeting WISP1. These findings suggested a novel treatment to overcome radioresistance in prostate cancer patients, especially those with higher levels of the WISP1 expression.