Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran.
Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
Biol Trace Elem Res. 2024 Jul;202(7):3073-3085. doi: 10.1007/s12011-023-03892-w. Epub 2023 Oct 4.
Cancer, the leading cause of death worldwide, has witnessed significant advancements in treatment through targeted therapies. Among the proto-oncogenes prevalent in human cancers, KRAS stands out, and recent research has focused on long noncoding RNAs (lncRNAs) as regulators of miRNAs targeting the KRAS oncogene. This study specifically explores lncRNAs involved in the KRAS pathway in colorectal cancer (CRC). To investigate this, researchers employed iron oxide nanoparticles coated with glucose and conjugated with Oleuropein (FeO@Glu-Oleuropein NPs) to evaluate their impact on candidate lncRNAs associated with KRAS pathway deregulation. The study utilized TCGA data to identify genes affected by KRAS mutation and lncRNAs linked to KRAS in CRC. Enrichr and MsigDB databases helped identify relevant pathways. Genes with a correlation coefficient above 0.5 and a P-value less than 0.01 with candidate lncRNAs were selected. MTT and flow cytometry assays determined the anti-proliferative and apoptotic effects of FeO@Glu-Oleuropein NPs on CRC cells (SW480) and normal cells (HEK293). The findings showed that increased expression of FEZF1-AS1, GAS6-AS1, and LINC00920 correlated with mutated KRAS, and co-expressed genes were significantly involved in hypoxia, KRAS signaling, DNA repair, and IL-2/STAT5 signaling pathways. FeO@Glu-Oleuropein NPs exhibited higher toxicity toward cancer cells, with IC50 values of 92 μg/ml for SW480 and 281 μg/ml for HEK293. Flow cytometry analysis revealed a substantial increase in necrotic and apoptotic cells when treated with FeO@Glu-Oleuropein, along with down-regulation of GAS6-AS1, LINC00920, and FEZF1-AS1 lncRNAs in treated cells. In conclusion, this study highlights the therapeutic potential of FeO@Glu-Oleuropein on colon cancer cells in vitro. The identification of lncRNAs involved in the KRAS pathway provides insights into the underlying mechanisms and offers avenues for further research in targeted cancer therapies.
癌症是全球主要的死亡原因，通过靶向治疗已经取得了显著的进展。在人类癌症中常见的原癌基因中，KRAS 是一个突出的例子，最近的研究集中在长非编码 RNA（lncRNA）作为 KRAS 致癌基因靶向 miRNA 的调节剂。本研究专门探讨了结直肠癌（CRC）中 KRAS 通路相关的 lncRNA。为了研究这一点，研究人员使用了涂有葡萄糖并与橄榄苦苷结合的氧化铁纳米粒子（FeO@Glu-Oleuropein NPs）来评估它们对与 KRAS 通路失调相关的候选 lncRNA 的影响。该研究利用 TCGA 数据鉴定了受 KRAS 突变影响的基因和与 CRC 中 KRAS 相关的 lncRNA。Enrichr 和 MsigDB 数据库有助于鉴定相关途径。选择与候选 lncRNA 相关系数大于 0.5 且 P 值小于 0.01 的基因。MTT 和流式细胞术测定了 FeO@Glu-Oleuropein NPs 对 CRC 细胞（SW480）和正常细胞（HEK293）的抗增殖和凋亡作用。结果表明，FEZF1-AS1、GAS6-AS1 和 LINC00920 的表达增加与突变的 KRAS 相关，并且共表达基因显著参与了缺氧、KRAS 信号、DNA 修复和 IL-2/STAT5 信号通路。FeO@Glu-Oleuropein NPs 对癌细胞的毒性更高，SW480 的 IC50 值为 92μg/ml，HEK293 的 IC50 值为 281μg/ml。流式细胞术分析显示，用 FeO@Glu-Oleuropein 处理后坏死和凋亡细胞明显增加，同时处理细胞中 GAS6-AS1、LINC00920 和 FEZF1-AS1 lncRNA 的表达下调。总之，本研究强调了 FeO@Glu-Oleuropein 在体外对结肠癌细胞的治疗潜力。鉴定参与 KRAS 通路的 lncRNA 为深入了解潜在机制提供了线索，并为靶向癌症治疗的进一步研究提供了途径。
