微RNA对肿瘤干细胞自我更新的影响机制

肿瘤干细胞( CSC)的自我更新与肿瘤的形成、复发以及耐药有关.微RNA (miRNA)能够调控细胞周期,影响细胞命运.目前的研究已发现微RNA可通过直接调节相关的基因靶点作用于肿瘤干细胞的自我更新,同时可能通过影响Wnt、Notch、Hedgehog等信号传导途径参与调节肿瘤干细胞自我更新.     

肿瘤干细胞与microRNA的研究进展

肿瘤干细胞是肿瘤的起源性细胞, 具有高度的致瘤性和耐药性。微小RNA(microRNA或miRNA)是由21~25个核苷酸组成的内源性非编码单链RNA, 是基因表达调控因子, 参与许多生物功能的调节。最近的研究发现, microRNA参与肿瘤干细胞的分化、自我更新等生物学特性的调控。肿瘤干细胞和microRNAs可以作为肿瘤研究的一个新的切入点。本文就近年来的研究进展做简要综述。      

microRNA与胃癌肿瘤干细胞研究进展

胃癌肿瘤干细胞是胃癌细胞中能够引起肿瘤生长和维持自我更新及分化潜能的一小群细胞,常用的化疗、放疗等治疗措施难以将其杀灭.胃癌肿瘤干细胞能够有选择地启动肿瘤的生长等生物学行为,与胃癌的复发、转移及耐药性等密切相关,影响胃癌患者的治疗及预后.而在胃癌发生、发展过程中存在多种类型微RNA(miRNA)的异常表达(过表达或表达缺失),这些miRNA对胃癌细胞具有重要调控作用.同时,这些miRNA对胃癌肿瘤干细胞的生物学行为更是起到关键调控作用.本文综述了miRNA与胃癌肿瘤干细胞的研究进展,为未来胃癌治疗新策略的发展提供有力支持.     

m^(6)A RNA甲基化修饰与肿瘤干细胞关系的研究进展北大核心

N6-甲基腺苷(N^(6)-methyladeno sine,m^(6)A)作为一种可逆的转录后修饰,是真核生物mRNA中最为普遍的一种RNA修饰形式。肿瘤干细胞(cancer stem cell,CSC)是肿瘤中一群具有自我更新能力和分化潜能的细胞,在肿瘤复发、转移中起关键作用。近年来大量研究表明m^(6)A具有调节肿瘤干细胞干性的能力。本文对m^(6)A相关酶的特征及其对肿瘤干细胞的作用机制进行综述,为选择性消除肿瘤干细胞提供新的靶点及研究方向。     

微小RNA在肝细胞癌及肝癌干细胞中的作用

微小RNA (miRNA)是一类约22个核苷酸分子构成的非编码单链小RNA.miRNA能参与一系列重要的生物学活动,如早期胚胎与器官发育、细胞增殖与分化、细胞凋亡等.miRNA在肝细胞癌中表达异常,与肝癌发生发展和浸润转移密切相关.肝癌干细胞可能是肝癌复发和转移的根源,某些miRNA与肝癌干细胞的自我更新、多向分化及成...     

MicroRNA在肿瘤干细胞中的调控作用研究进展

肿瘤干细胞(CSCs)是导致肿瘤复发、转移和耐药的根源之一。microRNA(miRNAs)是一类小分子非编码RNA,可与靶mRNA的3’UTR区域结合而导致该mRNA分子的翻译受到抑制,参与多种生物功能的调节。最近的研究发现,miRNAs参与CSCs的分化、自我更新等生物学特性的调控。miRNAs可以作为CSCs研究的一个新的切入点。本文就近年来该方面的研究进展做简要综述。     

肿瘤干细胞研究进展

目的:了解近年来肿瘤千细胞的研究进展.方法:应用检索Pubmed数据库检索系统,以"肿瘤"、"干细胞"、"肿瘤干细胞"为关键词,检索1979-01-2008-12的相关文献,共检索到英文文献2 760条.纳入标准:1)肿瘤干细胞的表面标志、耐药机制、信号传导通路;2)肿瘤干细胞来源;3)肿瘤干细胞与肿瘤临床诊治的联系.根据纳入标准,最后精选33篇文献进行分析综述.结果:肿瘤干细胞能够自我更新和分化,具有特异的表面分子标志,对放化疗不敏感.肿瘤干细胞存在Wnt、Notch、Hedgehog、Bmi-1等调节细胞自我更新信号通路异常.肿瘤干细胞是维持肿瘤生长、复发和转移的根源,已经成为抗肿瘤研究的靶细胞.结论:肿瘤干细胞研究进展迅速,深入研究肿瘤干细胞的特性,对恶性肿瘤的诊断,治疗和预后评估具有重要意义.肿瘤干细胞理论将改变目前肿瘤的诊治模式.     

肿瘤干细胞的生物特性及其起源

肿瘤干细胞高表达抗氧化剂谷胱甘肽而降低活性氧水平,避免DNA损伤,从而抵制放疗作用.此外抑癌基因p53导致的DNA修复异常也参与调节肿瘤干细胞的永生化.本文总结肿瘤干细胞自我更新、异质性、耐药性等生物学特性,并对肿瘤干细胞起源的正常细胞突变和细胞融合假说进行综述.     

肿瘤干细胞的来源及调控

20世纪60年代Sterens观察到小鼠睾丸畸胎瘤来源于原始生殖细胞,从而提出了肿瘤起源于干细胞的理论。“肿瘤干细胞假说”包含两层含义:(1)肿瘤起源于它们的组织干细胞或胚细胞自我更新的失调节;(2)肿瘤包含具有干细胞特性的细胞亚群。近年来的研究表明,在白血病及部分实体瘤如乳     

Bmi1基因在干细胞和肿瘤发生中的作用

干细胞是一类具有自我更新能力并可向多种细胞、组织类型分化的细胞.Bmi1基因在维持干细胞的自我更新能力中起关键的作用.干细胞与很多肿瘤的发生有关.增强干细胞的自我更新能力可以改变干细胞的生物特性,进一步导致肿瘤的发生.     

miRNA-regulated cancer stem cells: understanding the property and the role of miRNA in carcinogenesis

Over the last few years, microRNAs (miRNA)-controlled cancer stem cells have drawn enormous attention. Cancer stem cells are a small population of tumor cells that possess the stem cell property of self-renewal. Recent data shows that miRNA regulates this small population of stem cells. In the present review, we explained different characteristics of cancer stem cells as well as miRNA regulation of self-renewal and differentiation in cancer stem cells. We also described the migration and tumor formation. Finally, we described the different miRNAs that regulate various types of cancer stem cells, such as prostate cancer stem cells, head and neck cancer stem cells, breast cancer stem cells, colorectal cancer stem cells, lung cancer stem cells, gastric cancer stem cells, pancreatic cancer stem cells, etc. Extensive research is needed in order to employ miRNA-based therapeutics to control cancer stem cell population in various cancers in the future.     

Self-renewal and solid tumor stem cells

Solid tumors arise in organs that contain stem cell populations. The tumors in these tissues consist of heterogeneous populations of cancer cells that differ markedly in their ability to proliferate and form new tumors. In both breast cancers and central nervous system tumors, cancer cells differ in their ability to form tumors. While the majority of the cancer cells have a limited ability to divide, a population of cancer stem cells that has the exclusive ability to extensively proliferate and form new tumors can be identified based on marker expression. Growing evidence suggests that pathways that regulate the self-renewal of normal stem cells are deregulated in cancer stem cells resulting in the continuous expansion of self-renewing cancer cells and tumor formation. This suggests that agents that target the defective self-renewal pathways in cancer cells might lead to improved outcomes in the treatment of these diseases.     

上皮细胞间质转化与肿瘤干细胞

Epithelial-mesenchymal transition (EMT) not only can endow cells migration and invasion characteristics, but also can make tumor cells obtain self-renewal ability and have the characteristics of stem cells, which might result in cancer stem cell (CSC). There are the same molecular mechanism and microenvironment between EMT and CSC, which have great clinic significances for the diagnosis and treatment of the aggressive cancers. Moreover, many studies show that miR-200 could regulate EMT and CSC, participate in the tumor invasion and metastasi, and promote the research of targeted cancer therapy.     

Normal stem cells and cancer stem cells: similar and different

The functional capabilities of normal stem cells and tumorigenic cancer cells are conceptually similar in that both cell types are able to proliferate extensively. Indeed, mechanisms that regulate the defining property of normal stem cells – self-renewal – also frequently mediate oncogenesis. These conceptual links are strengthened by observations in some cancers that tumorigenic cells can not only renew their malignant potential but also generate bulk populations of non-tumorigenic cells in a manner that parallels the development of differentiated progeny from normal stem cells. But cancer cells are not normal. Although tumorigenic cells and normal stem cells are similar in some ways, they are also fundamentally different in other ways. Understanding both shared and distinguishing mechanisms that regulate normal stem cell proliferation and tumor propagation is likely to reveal opportunities for improving the treatment of patients with cancer.     

The disparate role of BMP in stem cell biology

Stem cells share several characteristics of cancer cells including loss of contact inhibition and immortality. Therefore, stem cells represent an excellent model system in which to define the molecular mechanisms underlying cancer development and progression. Several signal transduction pathways including leukemia inhibitory factor, Wnt and FGF have been demonstrated to function in stem cell self-renewal and differentiation. However, more recently bone morphogenetic proteins (BMPs) have emerged as key regulators of stem cell fate commitment. Intriguingly, BMPs have disparate roles in regulating the biology of embryonic stem (ES) cells compared with neural crest stem cells (NCSCs). Furthermore, although BMPs block neural differentiation of ES cells from both mouse and human, they contribute to self-renewal specifically in mouse ES cells. These observations strongly suggest that combinations of extracellular factors regulate stem cells, and that crosstalk between intracellular signaling pathways precisely defines stem cell fate commitment. In this review, we focus on the role of BMP signaling in mouse and human ES cells compared with NCSCs. We then discuss how the molecular effectors of BMP signaling may contribute to cancer, and thus represent potential targets for therapeutic intervention.     

Profiling cancer stem cells using protein array technology

Since cancer cells and somatic stem cells share the biological characteristics of self-renewal and proliferation, it has been suggested that the principles of stem cell biology can be applied to improve our understanding of cancer biology. Recent studies have shown that the majority of cancers appear to originate from a small subset of cells that have the ability of self-renewal and to proliferate, namely 'cancer stem cells'. The isolation of cancer stem cells has been demonstrated using cell surface markers in haematopoietic and non-haematopoietic malignancies. Advances in protein array technologies have enabled the use of minuscule amounts of biological materials to profile these cells at the molecular level. Using a combination of protein arrays and cancer stem cell isolation techniques, a higher resolution molecular profiling can be performed, which might improve therapies targeting the cancer stem cells.     

Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo

A key characteristic of stem cells and cancer cells is their ability to self-renew. To test if Wnt signaling can regulate the self-renewal of both stem cells and cancer cells in the hematopoietic system, we developed mice that lack beta-catenin in their hematopoietic cells. Here we show that beta-catenin-deficient mice can form HSCs, but that these cells are deficient in long-term growth and maintenance. Moreover, beta-catenin deletion causes a profound reduction in the ability of mice to develop BCR-ABL-induced chronic myelogenous leukemia (CML), while allowing progression of acute lymphocytic leukemia (ALL). These studies demonstrate that Wnt signaling is required for the self-renewal of normal and neoplastic stem cells in the hematopoietic system.     

Tumour stem cell-targeted treatment: elimination or differentiation.

A wide range of studies suggest that most cancers are clonal and may represent the progeny of a single cell, a cancer stem cell (CSC) endowed with the capacity to maintain tumour growth. The concept of a cancer stem cell emerged decades ago, and the haematopoietic system is where it has mostly gained ground. More recently, CSC have been described in breast cancer and brain tumours. Growing evidence suggests that pathways regulating normal stem cell self-renewal and differentiation are also present in cancer cells and CSC. Malignant tumours can be viewed as an abnormal organ in which a small population of tumourigenic cancer stem cells have escaped the normal limits of self-renewal giving rise to abnormally differentiated cancer cells that contribute to tumour progression and growth. This new model has important implications for the study and treatment of cancer. Understanding the molecular circuitry which contributes to the maintenance of stem cells may provide an insight into the molecular mechanisms of cancer and thus new approaches for elimination or differentiation therapy. Therapies targeting CSC should focus on pathways such as Wnt, Shh and Notch which are required for the maintenance of cancer stem cells, but also on the ABC transporter family and other specific properties of cancer stem cells.