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miRNA-652 表达与结直肠癌放射反应的相关性:来自瑞典术前放疗直肠肿瘤患者研究。

Association of MicroRNA-652 Expression with Radiation Response of Colorectal Cancer: A Study from Rectal Cancer Patients in a Swedish Trial of Preoperative Radiotherapy.

机构信息

Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, 581 83 Linköping, Sweden.

Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Chettinad Hospital and Research Institute, Kelambakkam, Chennai, Tamil Nadu - 603103, India.

出版信息

Curr Gene Ther. 2023;23(5):356-367. doi: 10.2174/1566523223666230418111613.

Abstract

BACKGROUND

Radiotherapy is a standard adjuvant therapy in patients with progressive rectal cancer, but many patients are resistant to radiotherapy, leading to poor prognosis. Our study identified value on radiotherapy response and outcome in rectal cancer patients.

METHODS

expression was determined by qPCR in primary rectal cancer from 48 patients with and 53 patients without radiotherapy. The association of with biological factors and the prognosis was examined. The biological function of was identified through TCGA and GEPIA database searches. Two human colon cancer cell lines (HCT116 p53 and p53) were used for in vitro study. The molecular interactions of and tumor suppressor genes were studied through a computational approach.

RESULTS

In RT patients, expression was significantly decreased in cancers when compared to non-radiotherapy cases ( = 0.002). High expression in non-RT patients was with increased apoptosis marker ( = 0.036), ATM ( = 0.010), and DNp73 expression ( = 0.009). High expression was related to worse disease-free survival of non-radiotherapy patients, independent of gender, age, tumor stage, and differentiation ( = 0.028; HR = 7.398, 95% CI 0.217-3.786). The biological functional analysis further identified the prognostic value and potential relationship of with apoptosis in rectal cancer. expression in cancers was negatively related to WRAP53 expression ( = 0.022). After inhibition, the estimation of reactive oxygen species, caspase activity, and apoptosis in HCT116 p53 cells was significantly increased compared with HCT116 p53 cells after radiation. The results of the molecular docking analysis show that the miR652-CTNNBL1 and miR652-TP53 were highly stable.

CONCLUSION

Our findings suggest the potential value of expression as a marker for the prediction of radiation response and clinical outcome in rectal cancer patients.

摘要

背景

放疗是进展期直肠癌患者的标准辅助治疗方法,但许多患者对放疗有抵抗作用,导致预后不良。我们的研究旨在确定在直肠癌患者中放疗反应和预后的价值。

方法

通过 qPCR 测定 48 例接受放疗和 53 例未接受放疗的直肠原发性肿瘤中的表达。研究了与生物学因素和预后的关系。通过 TCGA 和 GEPIA 数据库搜索确定 的生物学功能。使用两种人结肠癌细胞系(HCT116 p53 和 p53)进行体外研究。通过计算方法研究 与肿瘤抑制基因的分子相互作用。

结果

在接受放疗的患者中,与未接受放疗的患者相比,癌症中 的表达明显降低(=0.002)。未接受放疗的患者中高表达与增加的凋亡标志物(=0.036)、ATM(=0.010)和 DNp73 表达(=0.009)相关。高表达与未接受放疗患者的无病生存不良相关,独立于性别、年龄、肿瘤分期和分化(=0.028;HR=7.398,95%CI 0.217-3.786)。生物学功能分析进一步确定了 在直肠癌中的预后价值和潜在的与凋亡的关系。癌症中 的表达与 WRAP53 的表达呈负相关(=0.022)。与辐射后 HCT116 p53 细胞相比,抑制 后,HCT116 p53 细胞中的活性氧估计、半胱氨酸天冬氨酸蛋白酶活性和凋亡明显增加。分子对接分析结果表明,miR652-CTNNBL1 和 miR652-TP53 高度稳定。

结论

我们的研究结果表明, 表达作为预测直肠癌患者放疗反应和临床结局的标志物具有潜在价值。

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