The reduction of DNA damage repair capacity in terminally differentiated cells may be involved in sensitivity to cancer chemotherapy drugs; however, the underlying molecular mechanism is still not fully understood. Herein, we evaluated the role of miR-638 in the regulation of DNA damage repair in terminally differentiated cells. Our results show that miR-638 expression was up-regulated during cellular terminal differentiation and involved in mediating DNA damage repair processes. Results from a luciferase reporting experiment show that structural maintenance of chromosomes (SMC)1A was a potential target of miR-638; this was verified by western blot assays during cell differentiation and DNA damage induction. Overexpression of miR-638 enhanced the sensitivity of cancer cells to cisplatin, thus reducing cell viability in response to chemotherapy drug treatment. Furthermore, miR-638 overexpression affected DNA damage repair processes by interfering with the recruitment of the DNA damage repair-related protein, γH2AX, to DNA break sites. These findings indicate that miR-638 might act as a sensitizer in cancer chemotherapy and accompany chemotherapy drugs to enhance chemotherapeutic efficacy and to improve the chance of recovery from cancer.

中文翻译：

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miR-638通过靶向终末分化细胞中的SMC1A表达来抑制DNA损伤修复

终末分化细胞中DNA损伤修复能力的降低可能与对癌症化疗药物的敏感性有关。然而，潜在的分子机制仍未完全了解。在本文中，我们评估了miR-638在调节终末分化细胞中DNA损伤修复中的作用。我们的结果表明，miR-638表达在细胞终末分化过程中被上调，并参与介导DNA损伤修复过程。荧光素酶报告实验的结果表明，染色体（SMC）1A的结构维持是miR-638的潜在靶点；细胞分化和DNA损伤诱导过程中的蛋白质印迹分析证实了这一点。miR-638的过度表达增强了癌细胞对顺铂的敏感性，因此降低了对化疗药物治疗的细胞活力。此外，miR-638过表达会干扰DNA损伤修复相关蛋白γH2AX募集到DNA断裂位点，从而影响DNA损伤修复过程。这些发现表明，miR-638可能在癌症化学疗法中充当敏化剂，并与化学疗法药物配合使用，以增强化学疗法的效力并提高从癌症中康复的机会。