研究miR-451a作为肿瘤抑制因子在结直肠癌细胞系免疫原性细胞死亡诱导和树突状细胞成熟中的潜在作用。

IF 6 2区 医学 Q1 ONCOLOGY
Mahdieh Azizi, Alireza Andalib, Marzieh Rezaei
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引用次数: 0

摘要

背景:结直肠癌(CRC)仍然是癌症相关死亡的主要原因,因为常规治疗经常受到治疗耐药性和免疫抑制肿瘤微环境(TME)的存在的阻碍。免疫治疗,特别是基于免疫原性细胞死亡(ICD)诱导的策略可以通过增强肿瘤免疫原性和促进T细胞浸润来激活TME,从而潜在地提高癌症免疫治疗在结直肠癌中的疗效。本研究探讨了miR-451a作为肿瘤抑制因子在CRC细胞系中释放ICD相关损伤相关分子模式和树突状细胞(dc)成熟中的潜力。方法:用奥沙利铂单独处理人CRC细胞系(SW48、SW1116、SW480和Caco-2),或用hsa-miR-451a模拟物、重组miRNA或hsa-miR-451a模拟物和奥沙利铂联合转染48小时。使用MTT测定细胞活力,通过膜联蛋白V和PI染色评估细胞凋亡。流式细胞术检测细胞表面钙调蛋白(CRT)水平,分析CD11c + CD86 + CD80 +成熟dc的百分比。此外,用发光法定量测定ATP水平,用ELISA法测定HMGB1水平。结果:我们的研究结果表明,与对照组和重组miRNA组相比,miR-451a的过表达显著增加了所有四种CRC细胞系的凋亡和CRT表面暴露,就像奥沙利铂观察到的效果一样(P结论:本研究的发现为miR-451a作为CRC肿瘤抑制剂的潜在作用提供了新的见解。通过研究其对四种不同CRC细胞系ICD的影响,我们全面分析了其对肿瘤细胞和免疫系统的影响。我们的研究结果表明,miR-451a诱导了ICD反应的某些特征,这些特征取决于细胞环境。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Investigating the potential role of miR-451a as a tumor suppressor in immunogenic cell death induction and dendritic cell maturation in colorectal cancer cell lines.

Investigating the potential role of miR-451a as a tumor suppressor in immunogenic cell death induction and dendritic cell maturation in colorectal cancer cell lines.

Investigating the potential role of miR-451a as a tumor suppressor in immunogenic cell death induction and dendritic cell maturation in colorectal cancer cell lines.

Investigating the potential role of miR-451a as a tumor suppressor in immunogenic cell death induction and dendritic cell maturation in colorectal cancer cell lines.

Investigating the potential role of miR-451a as a tumor suppressor in immunogenic cell death induction and dendritic cell maturation in colorectal cancer cell lines.

Investigating the potential role of miR-451a as a tumor suppressor in immunogenic cell death induction and dendritic cell maturation in colorectal cancer cell lines.

Investigating the potential role of miR-451a as a tumor suppressor in immunogenic cell death induction and dendritic cell maturation in colorectal cancer cell lines.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, as conventional therapies are frequently hampered by treatment resistance and the presence of an immunosuppressive tumor microenvironment (TME). Immunotherapy, particularly strategies based on immunogenic cell death (ICD) induction can activate the TME by enhancing tumor immunogenicity and promoting T cell infiltration, potentially improving the efficacy of cancer immunotherapies in CRC. This study investigates the potential of miR-451a as a tumor suppressor in the release of ICD associated damage-associated molecular patterns in CRC cell lines and maturation of dendritic cells (DCs).

Methods: Human CRC cell lines (SW48, SW1116, SW480, and Caco-2) were treated with oxaliplatin alone or transfected with the hsa-miR-451a mimic, scrambled miRNA, or a combination of the hsa-miR-451a mimic and oxaliplatin for 48 h. Cell viability was measured using MTT assays, and apoptosis was assessed through annexin V and PI staining. Flow cytometry was employed to evaluate calreticulin (CRT) levels on the cell surface and to analyze the percentages of CD11c + CD86 + CD80 + mature DCs. Additionally, ATP levels were quantified using a luminescence assay, and HMGB1 levels were measured by ELISA.

Results: Our results demonstrated that the overexpression of miR-451a significantly increased apoptosis and CRT surface exposure in all four CRC cell lines, like the effects observed with oxaliplatin, when compared to both the control and scrambled miRNA groups (P < 0.05, P < 0.01, P < 0.001, and P < 0.0001). However, the combination of miR-451a with oxaliplatin did not yield synergistic effects across all cell lines. Additionally, the ability of miR-451a to increase extracellular ATP and HMGB1 levels, as well as its effect on DC maturation, varied among cell lines.

Conclusions: The findings of this study presents novel insights into the potential role of miR-451a as a tumor-suppressive agent in CRC. By examining its effect on ICD across four different CRC cell lines, we provide a comprehensive analysis of its impact on both tumor cells and the immune system. Our results suggest that miR-451a induce certain characteristics of the ICD response, which vary depending on the cellular context.

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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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