Upregulation of let-7f-5p promotes chemotherapeutic resistance in colorectal cancer by directly repressing several pro-apoptotic proteins
Upregulation of let-7f-5p promotes chemotherapeutic resistance in colorectal cancer by directly repressing several pro-apoptotic proteins
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DOI：
10.3892/ol.2018.8410
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发表时间：
2018-06-01
期刊：
影响因子：
2.9
通讯作者：
Liu, Bin
中科院分区：
文献类型：
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作者：
Tie, Yateng;Chen, Chong;Liu, Bin
结直肠癌（Colorectal cancer，CRC）是世界范围内最常见的原发性恶性肿瘤之一。化疗耐药是结直肠癌治疗中的主要临床问题。因此，研究新的生物标志物来预测结直肠癌患者的化疗耐药性并促进其个体化治疗具有重要意义。目前的研究报告，let-7 f-5 p表达升高化疗耐药的CRC组织相比，化疗敏感的组织。此外，上调let-7 f-5 p可增加CRC细胞中抗凋亡蛋白B细胞淋巴瘤2（Bcl-2）和特大B细胞淋巴瘤（Bcl-xL）的表达水平，并降低caspase-3和caspase-9的活性。相反，下调let-7 f-5 p产生相反的效果。值得注意的是，结果表明let-7 f-5 p通过直接抑制几种促凋亡蛋白的表达来促进化疗抗性，所述促凋亡蛋白包括肿瘤蛋白p53、肿瘤蛋白p53诱导的核蛋白1、肿瘤蛋白p53诱导的核蛋白2和半胱天冬酶-3。因此，let-7 f-5 p增强CRC细胞对化疗药物的抗性的新机制已被揭示，表明沉默let-7 f-5 p可能成为针对CRC的有效治疗策略。
Colorectal cancer (CRC) is one of the most frequently occurring primary malignant tumors worldwide. Chemotherapeutic resistance is a major clinical problem in the treatment of CRC. Therefore, it is of great importance to investigate novel biomarkers that may predict chemoresistance and facilitate the development of individualized treatment for patients with CRC. The present study reported that let-7f-5p expression was elevated in chemotherapy-resistant CRC tissues compared with chemotherapy-sensitive tissues. Furthermore, upregulating let-7f-5p increased the expression levels of the anti-apoptotic proteins, B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL), and decreased the activity of caspase-3 and caspase-9 in CRC cells. By contrast, downregulating let-7f-5p yielded the opposite effect. Notably, the results indicated that let-7f-5p promoted chemotherapeutic resistance by directly repressing the expression of several pro-apoptotic proteins, including tumor protein p53, tumor protein p53-inducible nuclear protein 1, tumor protein p53-inducible nuclear protein 2 and caspase-3. Therefore, a novel mechanism by which let-7f-5p enhances the resistance of CRC cells to chemotherapeutics has been revealed, indicating that silencing let-7f-5p may become an effective therapeutic strategy against CRC.