School of Life Sciences and Key Laboratory of Bio-resources and Eco-environment, Ministry of Education, Sichuan University, Chengdu, 610064, China.
Cell Prolif. 2013 Feb;46(1):86-96. doi: 10.1111/cpr.12009.
The legume lectin family, one of the most extensively studied plant lectin families, has received increasing attention for the remarkable anti-tumor activities of its members for binding specific cancer cell surface glycoconjugates. MicroRNAs, a class of small, non-coding RNAs, control translation and stability of mRNAs at post-transcriptional and translational levels. To date, accumulating evidence has revealed that microRNAs are involved in progression of a number of human diseases, especially cancers. However, the molecular manners of microRNA-modulated apoptosis in legume lectin-treated cancer cells are still under investigation.
We performed in silico analyses to study the interactions between three typical legume lectins (ConA, SFL and SAL) and some specific sugar-containing receptors (for example, EGFR, TNFR1, HSP70 and HSP90). Additionally, we predicted some relevant microRNAs which could significantly regulate these aforementioned targetreceptors and thus inhibiting down-stream cancer-related signaling pathways.
The results showed that these three legume lectins could competitively bind sugar-containing receptors such as EGFR, TNFR1, HSP70 and HSP90 in two ways, via anti-apoptotic or survival pathways. On the one hand, the legume lectins could induce cancer cell death through triggering receptor-mediated signaling pathways, which resulted from indirect binding between legume lectins and mannoses resided in receptors. On the other hand, direct binding between legume lectins and receptors could lead to steric hindrance, which would disturb efficient interactions between them, and thus, the legume lectins would induce cancer cell death by triggering receptor-mediated signaling pathways. In addition, we identified several relevant microRNAs that regulated these targeted receptors, thereby ultimately causing cancer cell apoptosis.
These findings provide new perspectives for exploring microRNA-modulated cell death in legume lectin-treated cancer cells, which could be utilized in combination therapy for future cancer drug development.
豆科植物凝集素家族是研究最为广泛的植物凝集素家族之一，其成员能够与特定癌细胞表面糖缀合物结合，具有显著的抗肿瘤活性，因此受到越来越多的关注。microRNA 是一类小的非编码 RNA，能够在转录后和翻译水平上控制 mRNA 的翻译和稳定性。迄今为止，越来越多的证据表明，microRNA 参与了许多人类疾病，特别是癌症的进展。然而，在豆科植物凝集素处理的癌细胞中，microRNA 调节细胞凋亡的分子机制仍在研究中。
我们进行了计算机模拟分析，以研究三种典型的豆科植物凝集素（ConA、SFL 和 SAL）与一些特定的含糖受体（如 EGFR、TNFR1、HSP70 和 HSP90）之间的相互作用。此外，我们预测了一些能够显著调节上述靶受体的相关 microRNA，从而抑制下游与癌症相关的信号通路。
结果表明，这三种豆科植物凝集素可以通过两种方式与 EGFR、TNFR1、HSP70 和 HSP90 等含糖受体竞争结合，一种是通过抗凋亡或存活途径，另一种是通过直接结合受体导致空间位阻，从而干扰它们之间的有效相互作用，从而通过触发受体介导的信号通路诱导癌细胞死亡。此外，我们鉴定了几个能够调节这些靶受体的相关 microRNA，从而最终导致癌细胞凋亡。
这些发现为探索豆科植物凝集素处理的癌细胞中 microRNA 调节的细胞死亡提供了新的视角，可用于未来癌症药物开发的联合治疗。
