Alkharsan Abdulrasool M Hussein M S, Safaralizadeh Reza, Khalaj-Kondori Mohammad, HosseinpourFeizi Mohammadali
Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun;398(6):6929-6940. doi: 10.1007/s00210-024-03674-8. Epub 2024 Dec 19.
Colorectal cancer (CRC) is the third most common malignancy worldwide. Long noncoding RNAs (lncRNAs) are involved in several pathogenic pathways related to CRC. This study aimed to compare the expression profiles of HCG11, HCG15, and HCG18 genes in CRC patients before and after chemotherapy. Moreover, capecitabine's effects, which is a chemotherapeutic agent, were investigated on apoptosis, cell cycle, and the lncRNA expression in CRC using HT-29 cells. qRT-PCR was used to measure lncRNAs expression in patient and healthy tissues, and the HT-29 CRC cell line. Additionally, the diagnostic and prognostic utility of these lncRNAs were assessed using the ROC curve analysis. The MTT assay was used to evaluate the cytotoxicity of capecitabine, and by using flow cytometry, apoptosis induction and cell cycle progression were investigated. CRC patients expressed higher levels of HCG11 and HCG15 and lower levels of HCG18. Furthermore, those receiving capecitabine demonstrated a decrease in HCG11 and an increase in HCG18 expression. In the HT-29 cell line, capecitabine can also increase the expression of HCG18 and decrease the expression of HCG11 and HCG15. However, no statistically significant variations were determined in the expression of these lncRNAs in clinical variables. Additionally, the data show that HCG18 is a poor prognostic biomarker, and HCG11 and HCG18 are poor diagnostic biomarkers. Treatment with capecitabine caused an accumulation of sub-G1 cells, indicating a potent apoptotic effect on HT-29 cells. These findings confirmed capecitabine's anticancer effects and showed that it can increase HCG18 and reduce HCG11 and HCG15 expression.
结直肠癌（CRC）是全球第三大常见恶性肿瘤。长链非编码RNA（lncRNAs）参与了与CRC相关的多种致病途径。本研究旨在比较CRC患者化疗前后HCG11、HCG15和HCG18基因的表达谱。此外，使用HT-29细胞研究了化疗药物卡培他滨对CRC细胞凋亡、细胞周期和lncRNA表达的影响。采用qRT-PCR检测患者和健康组织以及HT-29 CRC细胞系中lncRNAs的表达。此外，使用ROC曲线分析评估这些lncRNAs的诊断和预后效用。采用MTT法评估卡培他滨的细胞毒性，并通过流式细胞术研究细胞凋亡诱导和细胞周期进程。CRC患者中HCG11和HCG15表达水平较高，而HCG18表达水平较低。此外，接受卡培他滨治疗的患者HCG11表达降低，HCG18表达增加。在HT-29细胞系中，卡培他滨也可增加HCG18的表达，降低HCG11和HCG15的表达。然而，这些lncRNAs的表达在临床变量中未发现统计学上的显著差异。此外，数据显示HCG18是一种不良预后生物标志物，而HCG11和HCG18是不良诊断生物标志物。卡培他滨治疗导致亚G1期细胞积累，表明对HT-29细胞有显著的凋亡作用。这些发现证实了卡培他滨的抗癌作用，并表明它可增加HCG18表达，降低HCG11和HCG15表达。
