Ma Shumin, Ren Naixia, Huang Qilai
Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 266237, China.
Cancers (Basel). 2021 Jul 26;13(15):3752. doi: 10.3390/cancers13153752.
Numerous genetic variants located in autophagy-related genes have been identified for association with various cancer risks, but the biological mechanisms underlying these associations remain largely unknown. Here we investigated their regulatory activity with a parallel reporter gene assay system in breast cancer cells and identified multiple regulatory SNP sites, including rs10514231. It was located in the second intron of and showed gene regulatory activity in most breast cancer cells we used. Mechanistically, the T allele of rs10514231 led to downregulation by decreasing the binding affinity of TCF7L2. Overexpression of the gene in cancer cells diminished cell proliferation, migration, and invasion. Notably, downregulation correlated with breast cancer risk and with poor prognosis in patients. These results provide a plausible mechanism behind the association of rs10514231 with breast cancer risk and will be important for more effective therapeutic target identification for precision medicine.
已鉴定出位于自噬相关基因中的众多遗传变异与各种癌症风险相关，但这些关联背后的生物学机制仍 largely 未知。在此，我们使用平行报告基因检测系统在乳腺癌细胞中研究了它们的调控活性，并鉴定出多个调控 SNP 位点，包括 rs10514231。它位于[基因名称]的第二个内含子中，并且在我们使用的大多数乳腺癌细胞中显示出基因调控活性。从机制上讲，rs10514231 的 T 等位基因通过降低 TCF7L2 的结合亲和力导致[基因名称]下调。在癌细胞中过表达[基因名称]基因可减少细胞增殖、迁移和侵袭。值得注意的是，[基因名称]下调与乳腺癌风险以及患者的不良预后相关。这些结果为 rs10514231 与乳腺癌风险关联背后提供了一个合理的机制，并且对于更有效地识别精准医学的治疗靶点将具有重要意义。
原文中“largely”未翻译完整，可能是输入有误，推测完整单词为“largely”，意为“很大程度上”。此外，文中部分基因名称未明确给出，用[基因名称]表示。
