ANRIL lncRNA triggers efficient therapeutic efficacy by reprogramming the aberrant INK4-hub in melanoma
ANRIL lncRNA triggers efficient therapeutic efficacy by reprogramming the aberrant INK4-hub in melanoma
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ANRIL lncRNA 通过重新编程黑色素瘤中的异常 INK4-hub 触发有效的治疗效果
DOI：
10.1016/j.canlet.2016.07.024
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发表时间：
2016
期刊：
影响因子：
9.7
通讯作者：
Xianqun Fan
中科院分区：
文献类型：
--
作者：
Shiqiong Xu;Huixue Wang;Hui Pan;Yingyun Shi;Tianyuan Li;Shengfang Ge;Renbing Jia;He Zhang;Xianqun Fan
黑色素瘤是一种极具侵袭性的疾病，具有快速进展，高转移潜力和复发。同时纠正多种肿瘤特异性基因异常已成为开发治疗黑色素瘤的一种有吸引力的方法。为了增强抗黑色素瘤的活性，我们测试了一种“多米诺骨牌效应”的治疗方法，通过独特地靶向一个缺陷并自动触发其他缺陷的内源性纠正。利用这一策略，在9p21染色体上可疑的ink4b - arf - ink4基因簇中，在靶向抑制异常的anrillncrna后，异常的ink4b和ink4b缺陷同时被内源性自动纠正。在细胞培养中，与不治疗相比，这种治疗显著降低了肿瘤转移能力和肿瘤形成。在携带异种肿瘤的动物中，这种治疗方法显著抑制肿瘤生长并降低肿瘤重量。我们的研究结果揭示了一种新的治疗策略，通过重编程异常的ink4 -hub显著增强抗黑色素瘤的效率。
Melanoma is an extremely aggressive disease with rapid progression, high metastatic potential and recurrence. Simultaneous correction of multiple tumor-specific gene abnormalities has become an attractive approach for developing therapeutics to treat melanoma. To potentiate anti-melanoma activity, we tested a “domino effect-like” therapeutic approach by uniquely targeting one defect and automatically triggering the endogenous corrections of other defects. Using this strategy, in a suspiciousINK4b–ARF–INK4agene cluster at chromosome 9p21, aberrantINK4aandINK4bdefects were simultaneously endogenously auto-corrected after targeting the suppression of abnormalANRILlncRNA. In cell culture, this treatment significantly reduced the tumor metastatic capacity and tumor formation compared with absence of treatment. In animals harboring tumor xenografts, this therapeutic approach significantly inhibited tumor growth and reduced the tumor weight. Our results reveal a novel therapeutic strategy that significantly potentiates anti-melanoma efficiency by reprogramming the aberrantINK4-hub.