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RhoA-ROCK2 signaling possesses complex pathophysiological functions in cancer progression and shows promising therapeutic potential. RhoA-ROCK2 信号在癌症进展过程中具有复杂的病理生理功能,并显示出巨大的治疗潜力。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-14 DOI: 10.1186/s12935-024-03519-7
Yidi Ning, Minying Zheng, Yue Zhang, Yuqi Jiao, Jiangping Wang, Shiwu Zhang

The Rho GTPase signaling pathway is responsible for cell-specific processes, including actin cytoskeleton organization, cell motility, cell division, and the transcription of specific genes. The implications of RhoA and the downstream effector ROCK2 in cancer epithelial-mesenchymal transition, migration, invasion, and therapy resistance associated with stem cells highlight the potential of targeting RhoA/ROCK2 signaling in therapy. Tumor relapse can occur due to cancer cells that do not fully respond to adjuvant chemoradiotherapy, targeted therapy, or immunotherapy. Rho signaling-mediated mitotic defects and cytokinesis failure lead to asymmetric cell division, allowing cells to form polyploids to escape cytotoxicity and promote tumor recurrence and metastasis. In this review, we elucidate the significance of RhoA/ROCK2 in the mechanisms of cancer progression and summarize their inhibitors that may improve treatment strategies.

Rho GTPase信号通路负责细胞特异性过程,包括肌动蛋白细胞骨架组织、细胞运动、细胞分裂和特定基因的转录。RhoA和下游效应物ROCK2在癌症上皮-间充质转化、迁移、侵袭以及与干细胞相关的耐药性中的作用,凸显了靶向RhoA/ROCK2信号在治疗中的潜力。肿瘤复发可能是由于癌细胞对辅助化放疗、靶向治疗或免疫治疗没有完全反应。Rho 信号介导的有丝分裂缺陷和细胞分裂失败会导致细胞不对称分裂,使细胞形成多倍体以逃避细胞毒性并促进肿瘤复发和转移。在这篇综述中,我们阐明了 RhoA/ROCK2 在癌症进展机制中的重要作用,并总结了可改善治疗策略的抑制剂。
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引用次数: 0
Dysregulation of pseudouridylation in small RNAs contributes to papillary thyroid carcinoma metastasis. 小核糖核酸假苷酸化失调导致甲状腺乳头状癌转移
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-14 DOI: 10.1186/s12935-024-03482-3
Xi Wang, Hengyuan Gao, Wenjun Pu, Zhipeng Zeng, Nan Xu, Xunpeng Luo, Donge Tang, Yong Dai

Background: Previous studies have indicated that ψ-modified small RNAs play crucial roles in tumor metastasis. However, the ψ-modified small RNAs during metastasis of PTC are still unclear.

Methods: We compared the pseudouridine synthase 7 (PUS7) alteration between metastatic and non-metastatic PTCs, and investigated its correlation with clinicopathological features. Additionally, we employed a small RNA ψ modification microarray to examine the small RNA ψ modification profile in both metastatic and non-metastatic PTCs, as well as paired paracancerous tissues. The key molecule involved in ψ modification, pre-miR-8082, was identified and found to regulate the expression of CD47. Experiments in vitro were conducted to further investigate the function of PUS7 and CD47 in PTC.

Results: Our results demonstrated that PUS7 was down-regulated in PTC and was closely associated with metastasis. Moreover, the ψ modification of pre-miR-8082 was found to be decreased, resulting in down-expression of pre-miR-8082 and miR-8082, leading to the loss of the inhibitory effect on CD47, thereby promoting tumor migration.

Conclusions: Our study demonstrates that PUS7 promotes the inhibition of CD47 and inhibits metastasis of PTC cells by regulating the ψ modification of pre-miR-8082. These results suggest that PUS7 and ψ pre-miR-8082 may serve as potential targets and diagnostic markers for PTC metastasis.

背景:以往的研究表明,ψ修饰的小RNA在肿瘤转移中起着至关重要的作用。然而,PTC 转移过程中的ψ修饰小 RNA 仍不清楚:方法:我们比较了转移性和非转移性PTC的假尿苷合成酶7(PUS7)改变,并研究了其与临床病理特征的相关性。此外,我们还利用小 RNA ψ修饰芯片研究了转移性和非转移性 PTC 以及配对癌旁组织的小 RNA ψ修饰概况。研究发现了参与ψ修饰的关键分子pre-miR-8082,并发现它能调控CD47的表达。为了进一步研究 PUS7 和 CD47 在 PTC 中的功能,我们进行了体外实验:结果:我们的研究结果表明,PUS7在PTC中下调,并与转移密切相关。此外,研究还发现pre-miR-8082的ψ修饰减少,导致pre-miR-8082和miR-8082下调,从而失去对CD47的抑制作用,进而促进肿瘤迁移:我们的研究表明,PUS7通过调节pre-miR-8082的ψ修饰,促进对CD47的抑制并抑制PTC细胞的转移。这些结果表明,PUS7 和 ψ pre-miR-8082 可作为 PTC 转移的潜在靶点和诊断标志物。
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引用次数: 0
Serum exosomal small nucleolar RNA (snoRNA) signatures as a predictive biomarker for benign and malignant pulmonary nodules. 血清外泌体小核RNA(snoRNA)特征作为良性和恶性肺结节的预测性生物标记物。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-14 DOI: 10.1186/s12935-024-03522-y
Fei Cao, Qian You, Feng Zhu, Yu Zhang

Low-dose CT (LDCT) is increasingly recognized as the preferred method for detecting pulmonary nodules. However, distinguishing whether a nodule is benign or malignant often necessitates repeated scans or invasive tissue sampling procedures. Therefore, there is a pressing need for non-invasive techniques to minimize unnecessary interventions. This study aim to investigate the expression profile of exosomal snoRNA in the serum of patients with benign and malignant pulmonary nodules. We identified a total of 278 snoRNAs in serum exosomes, revealing significant differences in snoRNA levels between patients with malignant and benign nodules. Specifically, the upregulated snoRNAs U78 and U37 were validated through qRT-PCR and were found significantly elevated in the serum of patients with malignant pulmonary nodules, positioning them as promising biomarkers for the early detection of lung cancer. This study underscores the potential of serum exosomal U78 and U37 as critical tools for assessing the risk of pulmonary nodules identified through CT screening.

低剂量 CT(LDCT)越来越被认为是检测肺结节的首选方法。然而,要区分结节是良性还是恶性,往往需要反复扫描或进行侵入性组织取样手术。因此,迫切需要无创技术来减少不必要的干预。本研究旨在调查良性和恶性肺结节患者血清中外泌体 snoRNA 的表达谱。我们在血清外泌体中共鉴定出 278 个 snoRNA,发现恶性和良性结节患者的 snoRNA 水平存在显著差异。特别是,通过 qRT-PCR 验证,发现恶性肺结节患者血清中上调的 snoRNA U78 和 U37 显著升高,这两个 snoRNA 有希望成为早期检测肺癌的生物标志物。这项研究强调了血清外泌体 U78 和 U37 作为评估 CT 筛查发现的肺结节风险的重要工具的潜力。
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引用次数: 0
Hypoxia-related lncRNA correlates with prognosis and immune microenvironment in uveal melanoma. 缺氧相关lncRNA与葡萄膜黑色素瘤的预后和免疫微环境有关
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-09 DOI: 10.1186/s12935-024-03509-9
Yu Chen, Shen Chen, Zhenkai Wu, Quan Cheng, Dan Ji

Background: Hypoxia-related genes are linked to the prognosis of various solid malignant tumors. However, the role of hypoxia-related long non-coding RNAs (HRLs) in uveal melanoma (UVM) remains unclear. This study aimed to identify HRLs associated with UVM prognosis and develop a novel risk signature to predict patient outcomes.

Methods: Data from 80 UVM samples were obtained from The Cancer Genome Atlas. Prognostic HRLs were screened using Cox univariate and Pearson correlation analyses. HRL signature were constructed using Lasso analysis, and gene enrichment analysis was performed to explore the association between HRLs and immune features. Cell Counting Kit-8 assay was used to measure the propagation of human uveal melanoma (MuM2B) cells, while tumor invasion and migration were evaluated using Transwell and wound-healing experiments. Inflammatory factors and macrophage polarization were evaluated using quantitative PCR.

Results: In total, 621 prognostic HRLs were screened and constructed in 12 HRLs. The risk score showed a significant correlation with the survival time of patients with UVM. Additionally, HRL correlated with diverse key immune checkpoints, revealing possible targets for immunotherapy. Immune-related pathways were highly enriched in the high-risk group. LINC02367, a protective HRL, was associated with the tumor microenvironment and survival time of patients with UVM. In vitro, LINC02367 significantly influenced MuM2B proliferation and migration. It also modulated macrophage polarization by regulating inflammatory factor levels, thereby affecting the immune microenvironment.

Conclusions: We developed a novel HRL signature to predict prognosis in patients with UVM. HRLs are potential biomarkers and therapeutic targets for the treatment of UVM.

背景:缺氧相关基因与各种实体恶性肿瘤的预后有关。然而,缺氧相关长非编码 RNA(HRLs)在葡萄膜黑色素瘤(UVM)中的作用仍不清楚。本研究旨在鉴定与葡萄膜黑色素瘤预后相关的HRLs,并开发一种新的风险特征来预测患者的预后:方法:从癌症基因组图谱(The Cancer Genome Atlas)中获得了80个UVM样本的数据。利用Cox单变量分析和Pearson相关分析筛选出预后相关的HRL。利用Lasso分析构建了HRL特征,并进行了基因富集分析,以探索HRL与免疫特征之间的关联。细胞计数试剂盒-8测定了人葡萄膜黑色素瘤(MuM2B)细胞的繁殖,Transwell和伤口愈合实验评估了肿瘤的侵袭和迁移。利用定量 PCR 评估了炎症因子和巨噬细胞极化:结果:共筛选出621个预后HRL,并在12个HRL中构建了预后HRL。风险评分与 UVM 患者的生存时间有明显相关性。此外,HRL与多种关键免疫检查点相关,揭示了免疫疗法的可能靶点。免疫相关通路在高风险组中高度富集。LINC02367是一种保护性HRL,它与UVM患者的肿瘤微环境和生存时间有关。在体外,LINC02367能显著影响MuM2B的增殖和迁移。它还通过调节炎症因子水平来调节巨噬细胞的极化,从而影响免疫微环境:我们发现了一种新的HRL特征,可用于预测紫癜患者的预后。HRL是治疗紫癜的潜在生物标志物和治疗靶点。
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引用次数: 0
The axis of tumor-associated macrophages, extracellular matrix proteins, and cancer-associated fibroblasts in oncogenesis. 肿瘤相关巨噬细胞、细胞外基质蛋白和癌症相关成纤维细胞在肿瘤发生中的轴心作用。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-07 DOI: 10.1186/s12935-024-03518-8
Shuhong Yu, Siyu Wang, Xuanyu Wang, Ximing Xu

The extracellular matrix (ECM) is a complex, dynamic network of multiple macromolecules that serve as a crucial structural and physical scaffold for neighboring cells. In the tumor microenvironment (TME), ECM proteins play a significant role in mediating cellular communication between cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). Revealing the ECM modification of the TME necessitates the intricate signaling cascades that transpire among diverse cell populations and ECM proteins. The advent of single-cell sequencing has enabled the identification and refinement of specific cellular subpopulations, which has substantially enhanced our comprehension of the intricate milieu and given us a high-resolution perspective on the diversity of ECM proteins. However, it is essential to integrate single-cell data and establish a coherent framework. In this regard, we present a comprehensive review of the relationships among ECM, TAMs, and CAFs. This encompasses insights into the ECM proteins released by TAMs and CAFs, signaling integration in the TAM-ECM-CAF axis, and the potential applications and limitations of targeted therapies for CAFs. This review serves as a reliable resource for focused therapeutic strategies while highlighting the crucial role of ECM proteins as intermediates in the TME.

细胞外基质(ECM)是由多种大分子组成的复杂动态网络,是邻近细胞的重要结构和物理支架。在肿瘤微环境(TME)中,ECM 蛋白在介导癌症相关成纤维细胞(CAFs)和肿瘤相关巨噬细胞(TAMs)之间的细胞通讯方面发挥着重要作用。要揭示 TME 的 ECM 修饰,就必须了解不同细胞群和 ECM 蛋白之间错综复杂的信号级联。单细胞测序技术的出现使特定细胞亚群的鉴定和细化成为可能,这大大提高了我们对错综复杂的环境的理解,并为我们提供了有关 ECM 蛋白多样性的高分辨率视角。然而,整合单细胞数据并建立一个连贯的框架至关重要。为此,我们对 ECM、TAMs 和 CAFs 之间的关系进行了全面综述。这包括对 TAMs 和 CAFs 释放的 ECM 蛋白、TAM-ECM-CAF 轴的信号整合以及 CAFs 靶向疗法的潜在应用和局限性的深入了解。本综述是重点治疗策略的可靠资源,同时强调了 ECM 蛋白作为 TME 中间体的关键作用。
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引用次数: 0
Therapeutic combinations of exosomes alongside cancer stem cells (CSCs) and of CSC-derived exosomes (CSCEXs) in cancer therapy. 外泌体与癌症干细胞(CSCs)以及癌症干细胞衍生外泌体(CSCEXs)在癌症治疗中的治疗组合。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-05 DOI: 10.1186/s12935-024-03514-y
Arefeh Zabeti Touchaei, Seyedeh Elham Norollahi, Ali Najafizadeh, Kosar Babaei, Elahe Bakhshalipour, Sogand Vahidi, Ali Akbar Samadani

Exosomes which are membrane vesicles released by cells have gained significant interest in the field of cancer therapy as a novel means of intercellular communication. Their role in immune activation and their pathophysiological functions in cancer therapy have been recognized. Exosomes carry diverse bioactive components including proteins, mRNA, microRNAs, and bioactive lipids. These molecules have therapeutic potential in promoting tissue regeneration, supporting stem cell activity, preventing cell death, modulating immune responses, and promoting the growth of new blood vessels. However, the precise roles of exosomes derived from mesenchymal stem cells (MSCs) in the treatment of various cancers are still not fully understood. Consequently, cancer stem cells (CSCs) can self-renew and differentiate into various cell types. Understanding the mechanisms that sustain their persistence is crucial for developing effective therapies. Exosomes have recently gained interest as vehicles for intercellular communication between CSCs and non-CSCs, influencing cancer progression and the microenvironment. Research is ongoing on the utilization of exosomes derived from cancer stem cells (CSC-Exosome) for cancer treatment. The composition of extracellular vesicles is influenced by the specific type and condition of the cells from which they are secreted. Circulating exosomes contain stable RNA molecules such as mRNAs, microRNAs, and long non-coding RNAs (lncRNAs). In this review, we will explore the significance of exosomes and their diverse cellular combinations in the context of cancer therapy.

外泌体是由细胞释放的膜囊泡,作为一种新型的细胞间通信手段,外泌体在癌症治疗领域备受关注。它们在免疫激活中的作用及其在癌症治疗中的病理生理功能已得到认可。外泌体携带多种生物活性成分,包括蛋白质、mRNA、microRNA 和生物活性脂质。这些分子在促进组织再生、支持干细胞活性、防止细胞死亡、调节免疫反应和促进新血管生长方面具有治疗潜力。然而,间充质干细胞(MSCs)产生的外泌体在治疗各种癌症中的确切作用仍未完全明了。因此,癌症干细胞(CSCs)可以自我更新并分化成各种细胞类型。了解维持其持续存在的机制对于开发有效疗法至关重要。最近,外泌体作为癌干细胞与非癌干细胞之间进行细胞间交流、影响癌症进展和微环境的载体,引起了人们的兴趣。目前正在研究如何利用来自癌症干细胞的外泌体(CSC-Exosome)治疗癌症。细胞外囊泡的组成受其分泌细胞的特定类型和状态的影响。循环外泌体含有稳定的RNA分子,如mRNA、microRNA和长非编码RNA(lncRNA)。在这篇综述中,我们将探讨外泌体及其不同细胞组合在癌症治疗中的意义。
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引用次数: 0
Non-coding RNAs as potential targets in metformin therapy for cancer. 作为二甲双胍治疗癌症潜在靶点的非编码 RNA。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.1186/s12935-024-03516-w
Yihan Zhang, Yunhao Wu, Zixu Liu, Kangping Yang, Hui Lin, Kai Xiong

Metformin, a widely used oral hypoglycemic drug, has emerged as a potential therapeutic agent for cancer treatment. While initially known for its role in managing diabetes, accumulating evidence suggests that metformin exhibits anticancer properties through various mechanisms. Several cellular or animal experiments have attempted to elucidate the role of non-coding RNA molecules, including microRNAs and long non-coding RNAs, in mediating the anticancer effects of metformin. The present review summarized the current understanding of the mechanisms by which non-coding RNAs modulate the response to metformin in cancer cells. The regulatory roles of non-coding RNAs, particularly miRNAs, in key cellular processes such as cell proliferation, cell death, angiogenesis, metabolism and epigenetics, and how metformin affects these processes are discussed. This review also highlights the role of lncRNAs in cancer types such as lung adenocarcinoma, breast cancer, and renal cancer, and points out the need for further exploration of the mechanisms by which metformin regulates lncRNAs. In addition, the present review explores the potential advantages of metformin-based therapies over direct delivery of ncRNAs, and this review highlights the mechanisms of non-coding RNA regulation when metformin is combined with other therapies. Overall, the present review provides insights into the molecular mechanisms underlying the anticancer effects of metformin mediated by non-coding RNAs, offering novel opportunities for the development of personalized treatment strategies in cancer patients.

二甲双胍是一种广泛使用的口服降糖药,已成为一种潜在的癌症治疗药物。虽然二甲双胍最初因其在控制糖尿病方面的作用而为人所知,但越来越多的证据表明,二甲双胍通过各种机制表现出抗癌特性。一些细胞或动物实验试图阐明非编码 RNA 分子(包括 microRNA 和长非编码 RNA)在介导二甲双胍抗癌作用中的作用。本综述总结了目前对非编码 RNA 调节癌细胞对二甲双胍反应的机制的认识。讨论了非编码 RNA,尤其是 miRNA 在细胞增殖、细胞死亡、血管生成、新陈代谢和表观遗传学等关键细胞过程中的调控作用,以及二甲双胍如何影响这些过程。本综述还强调了 lncRNA 在肺腺癌、乳腺癌和肾癌等癌症类型中的作用,并指出有必要进一步探讨二甲双胍调控 lncRNA 的机制。此外,本综述还探讨了基于二甲双胍的疗法相对于直接给药 ncRNAs 的潜在优势,本综述还强调了二甲双胍与其他疗法联合使用时非编码 RNA 的调控机制。总之,本综述深入探讨了非编码 RNA 介导的二甲双胍抗癌作用的分子机制,为癌症患者个性化治疗策略的开发提供了新的机遇。
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引用次数: 0
Comprehensive analysis of bulk, single-cell RNA sequencing, and spatial transcriptomics revealed IER3 for predicting malignant progression and immunotherapy efficacy in glioma. 通过对体细胞、单细胞 RNA 测序和空间转录组学的综合分析,发现 IER3 可用于预测胶质瘤的恶性进展和免疫疗法疗效。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.1186/s12935-024-03511-1
Qi Wang, Chunyu Zhang, Ying Pang, Meng Cheng, Rui Wang, Xu Chen, Tongjie Ji, Yuntong Yang, Jing Zhang, Chunlong Zhong

Background: As part of stress-triggered molecules, immediate early response 3 (IER3) dysregulation has been reported to sustain pro-oncogenic pathways and precede malignant transformation. However, the role of IER3 in glioma pathology is ill-defined.

Methods: Immunohistochemistry (IHC) assay and publicly available glioma datasets were used to calculate the IER3 expression level in glioma. Wound healing, invasion and cell counting kit-8 (CCK8) assays were applied to measure the cell viability and capacities of migration and invasion of glioma cells in vitro. The immunofluorescence (IF) assay was used to assess the expression associations of IER3 with CCL2 and TGFBI. Cox regression analysis and Kaplan-Meier (K-M) curve were introduced to compute the prognosis-predicting value of IER3. Variations in copy number (CNVs), single nucleotide (SNVs), and methylation profiles were analyzed to illustrate the epigenetic modifications of IER3. Gliomas were divided into two subgroups using the restricted cubic spline (RCS) method. RESULTS IER3: was overexpressed and hypomethylated in gliomas and significantly associated with the dismal prognosis of glioma samples. Samples in the high IER3 subgroup were characterized by increased infiltration of tumor-associated monocytes/macrophages (TAMMs), as well as the elevated sensitivity to Dabrafenib, an inhibitor of BRAF. In addition, this subgroup demonstrated a low mutation rate of IDH, high gain rates of BRAF, ELTD1, and PDGFA. Gliomas with relatively low IER3 expression demonstrated a less invasive subtype and were featured by favorable prognosis, increased response to immunotherapy, and adjuvant chemotherapy plus radiotherapy. The IF assay revealed that IER3 was co-localized and co-expressed with TGFBI. The glioma cells with small interfering RNA (siRNA)-silenced IER3 displayed lower migration, invasion, proliferation, and cell viability than the control group.

Conclusions: In this study, we identified IER3 upregulation as an essential biomarker that could assist in adjuvant therapy and prognosis prediction for gliomas.

背景:据报道,作为应激触发分子的一部分,即时早期反应3(IER3)失调可维持促癌通路,并在恶性转化之前发生。然而,IER3 在胶质瘤病理学中的作用尚不明确:方法:使用免疫组化(IHC)检测和公开的胶质瘤数据集来计算胶质瘤中IER3的表达水平。采用伤口愈合、侵袭和细胞计数试剂盒-8(CCK8)测定法来测量胶质瘤细胞在体外的活力以及迁移和侵袭能力。免疫荧光(IF)测定用于评估IER3与CCL2和TGFBI的表达关系。研究引入了Cox回归分析和Kaplan-Meier(K-M)曲线来计算IER3的预后预测价值。分析了拷贝数(CNVs)、单核苷酸(SNVs)和甲基化的变化,以说明IER3的表观遗传学修饰。使用限制性立方样条(RCS)方法将胶质瘤分为两个亚组。结果 IER3:在胶质瘤中过表达和低甲基化,与胶质瘤样本的不良预后显著相关。高 IER3 亚组样本的特点是肿瘤相关单核细胞/巨噬细胞(TAMMs)浸润增加,以及对 BRAF 抑制剂达拉非尼(Dabrafenib)的敏感性升高。此外,该亚组的IDH突变率较低,BRAF、ELTD1和PDGFA的增益率较高。IER3表达相对较低的胶质瘤属于侵袭性较低的亚型,预后良好,对免疫疗法和辅助化疗加放疗的反应较强。IF检测显示,IER3与TGFBI共定位和共表达。与对照组相比,小干扰RNA(siRNA)沉默IER3的胶质瘤细胞显示出较低的迁移、侵袭、增殖和细胞活力:在这项研究中,我们发现IER3上调是一种重要的生物标志物,有助于胶质瘤的辅助治疗和预后预测。
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引用次数: 0
Decoding the immune microenvironment: unveiling CD8 + T cell-related biomarkers and developing a prognostic signature for personalized glioma treatment. 解码免疫微环境:揭示 CD8 + T 细胞相关生物标志物,为胶质瘤个性化治疗开发预后特征。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.1186/s12935-024-03517-9
Xiaofang Lin, Jianqiang Liu, Ni Zhang, Dexiang Zhou, Yakang Liu

Background: Gliomas are aggressive brain tumors with poor prognosis. Understanding the tumor immune microenvironment (TIME) in gliomas is essential for developing effective immunotherapies. This study aimed to identify TIME-related biomarkers in glioma using bioinformatic analysis of RNA-seq data.

Methods: In this study, we employed weighted gene co-expression network analysis (WGCNA) on bulk RNA-seq data to identify TIME-related genes. To identify prognostic genes, we performed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Based on these genes, we constructed a prognostic signature and delineated risk groups. To validate the prognostic signature, external validation was conducted.

Results: CD8 + T cell infiltration was strongly correlated with glioma patient prognosis. We identified 115 CD8 + T cell-related genes through integrative analysis of bulk-seq data. CDCA5, KIF11, and KIF4A were found to be significant immune-related genes (IRGs) associated with overall survival in glioma patients and served as independent prognostic factors. We developed a prognostic nomogram that incorporated these genes, age, gender, and grade, providing a reliable tool for clinicians to predict patient survival probabilities. The nomogram's predictions were supported by calibration plots, further validating its accuracy.

Conclusion: In conclusion, our study identifies CD8 + T cell infiltration as a strong predictor of glioma patient outcomes and highlights the prognostic value of genes. The developed prognostic nomogram, incorporating these genes along with clinical factors, provides a reliable tool for predicting patient survival probabilities and has important implications for personalized treatment decisions in glioma.

背景:胶质瘤是一种侵袭性脑肿瘤,预后较差。了解胶质瘤的肿瘤免疫微环境(TIME)对于开发有效的免疫疗法至关重要。本研究旨在通过对 RNA-seq 数据进行生物信息学分析,确定胶质瘤中与 TIME 相关的生物标记物:在这项研究中,我们对大量 RNA-seq 数据进行了加权基因共表达网络分析(WGCNA),以确定与 TIME 相关的基因。为了确定预后基因,我们进行了单变量 Cox 回归和最小绝对收缩与选择算子(LASSO)回归分析。根据这些基因,我们构建了预后特征并划分了风险组。为了验证预后特征,我们进行了外部验证:结果:CD8 + T细胞浸润与胶质瘤患者的预后密切相关。我们通过对大量序列数据进行整合分析,确定了115个CD8 + T细胞相关基因。发现 CDCA5、KIF11 和 KIF4A 是与胶质瘤患者总生存率相关的重要免疫相关基因(IRGs),并且是独立的预后因素。我们开发了一种预后提名图,将这些基因、年龄、性别和分级结合在一起,为临床医生预测患者的生存概率提供了一种可靠的工具。提名图的预测结果得到了校准图的支持,进一步验证了其准确性:总之,我们的研究确定了 CD8 + T 细胞浸润是胶质瘤患者预后的有力预测因素,并强调了基因的预后价值。所开发的预后提名图将这些基因与临床因素结合在一起,为预测患者的生存概率提供了可靠的工具,对胶质瘤的个性化治疗决策具有重要意义。
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引用次数: 0
Extracellular vesicle-mediated delivery of miR-766-3p from bone marrow stromal cells as a therapeutic strategy against colorectal cancer. 以细胞外囊泡为媒介从骨髓基质细胞中输送 miR-766-3p 作为结直肠癌治疗策略。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.1186/s12935-024-03493-0
Linsen Zhou, Xinyi Zhang, Zhiqiang Wang, Dongqing Li, Guangjun Zhou, Haofeng Liu

Objective: As colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths, understanding novel therapeutic mechanisms is crucial. This research focuses on the role of extracellular vesicles (EVs) from bone marrow stromal cells (BMSCs) in delivering miR-766-3p to CRC cells, targeting the MYC/CDK2 signaling axis.

Methods: Differentially expressed genes between BMSCs-EVs and CRC were identified using the Gene Expression Omnibus database. miR-766-3p target genes were predicted via TargetScan and RNAInter, with protein interactions analyzed using the STRING database. The analysis included RT-qPCR and Western blot on samples from 52 CRC patients. Characterization of BMSCs-EVs was followed by their functional assessment on CRC cell lines and the normal colon cell line CCD-18CO, evaluating cellular uptake, proliferation, migration, invasion, and apoptosis.

Results: miR-766-3p was confirmed in BMSCs-EVs and found underexpressed in CRC. BMSCs-EVs transported miR-766-3p to CRC cells, inhibiting their proliferation, migration, and invasion while promoting apoptosis. miR-766-3p targeted MYC, leading to decreased CDK2 transcription. Overexpression of MYC in HCT-116 cells counteracted these effects. In vivo studies showed that BMSCs-EVs carrying miR-766-3p hindered tumor growth.

Conclusion: The study demonstrates the efficacy of BMSCs-EVs in delivering miR-766-3p to CRC cells, leading to the suppression of the MYC/CDK2 signaling pathway and hindering cancer progression.

目的:结直肠癌(CRC)仍然是癌症相关死亡的主要原因之一,因此了解新的治疗机制至关重要。本研究的重点是骨髓基质细胞(BMSCs)的胞外囊泡(EVs)在向CRC细胞传递miR-766-3p、靶向MYC/CDK2信号轴中的作用:通过 TargetScan 和 RNAInter 预测 miR-766-3p 靶基因,并使用 STRING 数据库分析蛋白质相互作用。分析包括对 52 例 CRC 患者样本进行 RT-qPCR 和 Western 印迹。在对 BMSCs-EVs 进行表征后,还对其在 CRC 细胞系和正常结肠细胞系 CCD-18CO 上的功能进行了评估,评估了细胞吸收、增殖、迁移、侵袭和凋亡。BMSCs-EVs 将 miR-766-3p 运送到 CRC 细胞,抑制其增殖、迁移和侵袭,同时促进细胞凋亡。在 HCT-116 细胞中过表达 MYC 可抵消这些效应。体内研究表明,携带miR-766-3p的BMSCs-EV阻碍了肿瘤的生长:研究表明,BMSCs-EVs 能有效地向 CRC 细胞传递 miR-766-3p,从而抑制 MYC/CDK2 信号通路,阻碍癌症进展。
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Cancer Cell International
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