Department of Pathology, Qilu Hospital, Shandong University, Jinan, PR China; Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, PR China.
Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, PR China.
Cancer Lett. 2022 Jan 1;524:82-90. doi: 10.1016/j.canlet.2021.09.042. Epub 2021 Oct 7.
Long non-coding RNAs (lncRNAs) play important roles in cancer development and progression; however, their contributions to gastric cancer metastasis remain largely unknown. By lncRNA microarray screening, our study showed that 453 lncRNAs are dysregulated in gastric cancer tissues with or without lymph node metastasis, of which lnc-LEMGC ranks as one of the most significantly downregulated lncRNAs. Lnc-LEMGC inhibited cell migration and invasion both in vitro and in vivo, by combining with protein DNA-PKcs. Importantly, nucleotides 1300-1800 of lnc-LEMGC prevented DNA-PKcs phosphorylation of serine 2056 and partially abrogated the effects of downstream effectors, ErbB1, SRC and protein tyrosine kinase 2 (FAK), in the epidermal growth factor receptor (EGFR) pathway. The results of this study extend our knowledge of lncRNA's molecular mechanisms, in which lnc-LEMGC functions by directly suppressing the phosphorylation of its combined protein DNA-PKcs and inactivating the DNA-PKcs downstream EGFR signaling.
长链非编码 RNA（lncRNAs）在癌症的发生和发展中发挥着重要作用；然而，它们在胃癌转移中的贡献在很大程度上仍不清楚。通过 lncRNA 微阵列筛选，我们的研究表明，在有或没有淋巴结转移的胃癌组织中，有 453 个 lncRNAs 失调，其中 lnc-LEMGC 是下调最显著的 lncRNAs 之一。lnc-LEMGC 通过与蛋白 DNA-PKcs 结合，在体外和体内均抑制细胞迁移和侵袭。重要的是，lnc-LEMGC 的核苷酸 1300-1800 阻止了 DNA-PKcs 丝氨酸 2056 的磷酸化，并部分削弱了下游效应物，表皮生长因子受体（EGFR）通路中的 ErbB1、SRC 和蛋白酪氨酸激酶 2（FAK）的作用。本研究的结果扩展了我们对 lncRNA 分子机制的认识，其中 lnc-LEMGC 通过直接抑制与其结合的蛋白 DNA-PKcs 的磷酸化和使 DNA-PKcs 下游的 EGFR 信号失活来发挥作用。
