Maintenance of cancer stemness by miR-196b-5p contributes to chemoresistance of colorectal cancer cells via activating STAT3 signaling pathway.
Maintenance of cancer stemness by miR-196b-5p contributes to chemoresistance of colorectal cancer cells via activating STAT3 signaling pathway.
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miR-196b-5p维持癌症干性有助于通过激活STAT3信号通路增强结直肠癌细胞的化疗耐药性
DOI：
10.18632/oncotarget.17971
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发表时间：
2017-07-25
期刊：
影响因子：
--
通讯作者：
Zeng J
中科院分区：
文献类型：
--
作者：
Ren D;Lin B;Zhang X;Peng Y;Ye Z;Ma Y;Liang Y;Cao L;Li X;Li R;Sun L;Liu Q;Wu J;Zhou K;Zeng J
新兴的研究表明，癌症干细胞代表肿瘤内负责化疗耐药性的细胞亚群。然而，其潜在的机制仍不清楚。在这里，我们报告了miR-196 b-5 p在CRC组织中显著上调，并且miR-196 b-5 p的高表达与CRC患者的生存率低相关。此外，复发性增益（扩增）有助于CRC组织中miR-196 b-5 p的过表达。沉默miR-196 b-5 p可抑制结直肠癌细胞球体形成能力、SP细胞比例、干细胞因子表达和线粒体电位，增强5-氟尿嘧啶诱导的结直肠癌细胞凋亡;而异位表达miR-196 b-5 p则产生相反的作用。此外，miR-196 b-5 p的下调使CRC细胞在体内对5-氟尿嘧啶重新敏感。我们的研究结果进一步证明miR-196 b-5 p通过靶向STAT 3信号通路的负调控因子SOCS 1和SOCS 3，引起STAT 3信号通路的激活，促进CRC细胞的干细胞性和对5-氟尿嘧啶的化学抗性。有趣的是，与健康对照受试者相比，miR-196 b-5 p在CRC患者的血清外泌体中高度富集。因此，我们的研究结果揭示了miR-196 b-5 p参与维持CRC干细胞特性和化疗耐药性的新机制，为抗miR-196 b-5 p联合常规化疗治疗CRC提供了潜在的合理注册。
Emerging studies indicated that cancer stem cells represent a subpopulation of cells within the tumor that is responsible for chemotherapeutic resistance. However, the underlying mechanism is still not clarified yet. Here we report that miR-196b-5p is dramatically upregulated in CRC tissues and high expression of miR-196b-5p correlates with poor survival in CRC patients. Moreover, recurrent gains (amplification) contribute to the miR-196b-5p overexpression in CRC tissues. Silencing miR-196b-5p suppresses spheroids formation ability, the fraction of SP cells, expression of stem cell factors and the mitochondrial potential, and enhances the apoptosis induced by 5-fluorouracil in CRC cells; while ectopic expression of miR-196b-5p yields an opposite effect. In addition, downregulation of miR-196b-5p resensitizes CRC cells to 5-fluorouracil in vivo. Our results further demonstrate that miR-196b-5p promotes stemness and chemoresistance of CRC cells to 5-fluorouracil via targeting negative regulators SOCS1 and SOCS3 of STAT3 signaling pathway, giving rise to activation of STAT3 signaling. Interestingly, miR-196b-5p is highly enriched in the serum exosomes of patients with CRC compared to the healthy control subjects. Thus, our results unravel a novel mechanism of miR-196b-5p implicating in the maintenance of stem cell property and chemotherapeutic resistance in CRC, offering a potential rational registry of anti-miR-196b-5p combining with conventional chemotherapy against CRC.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
3.7
作者：
Boisen MK;Dehlendorff C;Linnemann D;Nielsen BS;Larsen JS;Osterlind K;Nielsen SE;Tarpgaard LS;Qvortrup C;Pfeiffer P;Holländer NH;Keldsen N;Hansen TF;Jensen BB;Høgdall EV;Jensen BV;Johansen JS
通讯作者：
Johansen JS
DOI：
10.1073/pnas.0603507103
发表时间：
2006-06-27
影响因子：
11.1
作者：
Kasprzycka, Monika;Marzec, Michal;Wasik, Mariusz A.
通讯作者：
Wasik, Mariusz A.
细胞间纳米层介导的microRNA转移：肝癌细胞生长的环境调节机制。
影响因子：
13.5
作者：
Kogure, Takayuki;Lin, Wen-Lang;Yan, Irene K.;Braconi, Chiara;Patel, Tushar
通讯作者：
Patel, Tushar
影响因子：
--
作者：
Hebenstreit, D;Horejs-Hoeck, J;Duschl, A
通讯作者：
Duschl, A