Lin28A enhances chemosensitivity of colon cancer cells to 5-FU by promoting apoptosis in a let-7 independent manner
Lin28A enhances chemosensitivity of colon cancer cells to 5-FU by promoting apoptosis in a let-7 independent manner
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Lin28A 通过以独立于 let-7 的方式促进细胞凋亡，增强结肠癌细胞对 5-FU 的化疗敏感性。
DOI：
10.1007/s13277-015-4559-8
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发表时间：
2016-06-01
期刊：
影响因子：
--
通讯作者：
Li, Xiaobo
中科院分区：
文献类型：
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作者：
Wang, Tianzhen;Han, Peng;Li, Xiaobo
RNA结合蛋白Lin 28 A在人类恶性肿瘤中频繁过表达，并与肿瘤进展和不良预后相关。然而，Lin 28 A在结肠癌中的表达模式和功能尚不清楚。本研究检测了Lin 28 A在结肠癌患者中的表达，并检测了Lin 28 A对结肠癌细胞对5-氟尿嘧啶（5-FU）化疗敏感性的影响。正如预期的那样，我们发现Lin 28 A在73.3%的结肠癌患者中上调。然而，令我们惊讶的是，我们发现致癌蛋白Lin 28 A在结肠癌细胞中的强制表达通过促进细胞凋亡而增强了癌细胞对5-FU的化疗敏感性。进一步的机制研究表明，Lin 28 A增加肿瘤细胞化疗敏感性的作用不依赖于let-7，但与降低DNA损伤修复蛋白H2 AX的表达有关。总之，在这里，我们报告了一个意想不到的功能Lin 28 A，这可能有助于充分了解这个癌基因的生理和病理作用。
RNA-binding protein Lin28A is frequently over-expressed in human malignant tumors and is associated with tumor advance and poor prognosis. However, the expression pattern and functions of Lin28A in colon cancer are unknown. In this study, we detected the expression of Lin28A in colon cancer patients and tested the effect of Lin28A on the chemotherapeutic sensitivity of colon cancer cells to 5-fluorouracil (5-FU). As expected, we showed that Lin28A is up-regulated in 73.3 % of colon cancer patients. However, to our surprise, we found that oncogenic protein Lin28A-enforced expression in colon cancer cells enhanced the chemosensitivity of cancer cells to 5-FU via promoting the cell apoptosis. Further mechanisms study revealed that the effect of Lin28A increasing chemosensitivity of cancer cells is in a let-7 independent manner, but which is associated with decreasing the expression of DNA damage repair protein H2AX. Conclusively, here we reported an unexpected function of Lin28A, which may shed lights on fully understanding the physiological and pathological roles of this oncogene.