Modified miR-15a has therapeutic potential for improving treatment of advanced stage colorectal cancer through inhibition of BCL2, BMI1, YAP1 and DCLK1.
Modified miR-15a has therapeutic potential for improving treatment of advanced stage colorectal cancer through inhibition of BCL2, BMI1, YAP1 and DCLK1.
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修饰的miR-15a通过抑制BCL2，BMI1，YAP1和DCLK1具有改善晚期结直肠癌治疗的治疗潜力。
DOI：
10.18632/oncotarget.23414
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发表时间：
2018-01-05
期刊：
影响因子：
--
通讯作者：
Ju J
中科院分区：
文献类型：
--
作者：
Fesler A;Liu H;Ju J
尽管结肠癌治疗取得了进展，但耐药性和复发仍然是治疗患者的重大挑战。迫切需要新的治疗策略来克服耐药性并改善患者结局。基于microRNA的疗法有可能帮助对抗耐药性。在这项研究中，我们已经证明了低miR-15a表达与患者预后不良相关。我们已经证明了miR-15a在结肠癌中的治疗潜力。miR-15a抑制几个重要基因（BCL 2，BMI1，YAP 1和DCLK1），减少癌症进展和耐药性。此外，通过用5-氟尿嘧啶取代miR-15a中的尿嘧啶，我们创建了具有增强的治疗潜力的新型miR-15a模拟物。该模拟物保持靶特异性，并且在体外比未修饰的miR-15a更有效，并且在体内抑制结肠肿瘤转移。这种模拟物具有治疗结肠癌患者的治疗开发的巨大潜力。这种新的修饰有可能促进miR-15a以外的其他基于microRNA的治疗方法的发展。
Despite advances in colon cancer treatments, resistance and recurrence remain a significant challenge in treating patients. Novel therapeutic strategies are in urgent need to overcome resistance and improve patient outcomes. MicroRNA based therapeutics have potential to help combat resistance. In this study, we have shown that low miR-15a expression correlates with poor patient prognosis. We have demonstrated the therapeutic potential of miR-15a in colon cancer. miR-15a inhibits several important genes (BCL2, BMI1, YAP1 and DCLK1), decreasing cancer progression and resistance. Additionally, by replacing uracil in miR-15a with 5-fluorouracil, we created a novel miR-15a mimic with enhanced therapeutic potential. This mimic maintains target specificity and is more potent than unmodified miR-15a in vitro and inhibits colon tumor metastasis in vivo. This mimic has great potential for therapeutic development for treating colon cancer patients. This novel modification has potential to advance the development of other microRNA based therapeutics beyond miR-15a.
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癌基因 YAP1 与结直肠癌患者的不良预后和西妥昔单抗耐药性显着相关。
DOI：
10.1158/1078-0432.ccr-14-1374
发表时间：
2015-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Lee KW;Lee SS;Kim SB;Sohn BH;Lee HS;Jang HJ;Park YY;Kopetz S;Kim SS;Oh SC;Lee JS
通讯作者：
Lee JS
影响因子：
2.8
作者：
Gagliardi, Giuseppe;Moroz, Krzysztof;Bellows, Charles F.
通讯作者：
Bellows, Charles F.
影响因子：
4.6
作者：
Lopez-Arribillaga, Erika;Rodilla, Veronica;Espinosa, Lluis
通讯作者：
Espinosa, Lluis
影响因子：
6.4
作者：
Sithanandam, Gunamani;Fornwald, Laura W.;Fields, Janet R.;Morris, Nicole L.;Anderson, Lucy M.
通讯作者：
Anderson, Lucy M.
影响因子：
64.5
作者：
LEE, RC;FEINBAUM, RL;AMBROS, V
通讯作者：
AMBROS, V