MicroRNA与乳腺癌干细胞

乳腺癌干细胞是导致乳腺癌复发、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。最近研究发现,miRNAs参与乳腺癌干细胞的分化、自我更新等生物学特性的调控。MiRNAs可以作为乳腺癌干细胞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。     

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.     

MicroRNA与乳腺癌干细胞的研究进展

乳腺癌是女性最常见的恶性肿瘤之一,尽管目前治疗手段的多样性,乳腺癌的复发及转移仍不断增加,使临床治疗遇到瓶颈,乳腺癌干细胞理论的提出为其治疗提供新的思路。MicroRNA作为一种非编码RNA,通过与靶基因mRNA结合影响转录及表达。随着对MicroRNA和乳腺癌干细胞的进一步研究,MicroRNA在乳腺癌干细胞中的功能日益突出,本文就MicroRNA与乳腺癌干细胞的研究进展及相互作用进行论述。     

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.     

肾癌干细胞与表观遗传学调控研究进展

针对肿瘤干细胞进行靶向治疗是遏止肿瘤复发和转移的关键。表观遗传学在干细胞发育及体细胞重编程中的重要作用提示其可能在肿瘤干细胞的发生发展中发挥作用。表观基因组包含DNA甲基化、组蛋白修饰、染色体重塑和非编码RNA调控的基因表达模式,在肾癌细胞中有多种表观基因组的异常改变。目前已成功的从肾细胞癌中获得SP细胞、细胞囊球和CD105+细胞等具肿瘤干细胞属性的细胞亚群。随着对肾细胞癌（renal cell carcinoma,RCC）遗传研究的不断深入,发现DNA序列以外的调控机制异常在肿瘤的发生发展过程中起重要的作用。对肾癌发生相关的表观遗传学的认识有助于推进新的治疗方式,而对发现新的预后和早期诊断标志将起更重要的作用。本文对目前肾癌干细胞和表观遗传学相关领域的最新研究,特别是肾癌干细胞发生和发展过程中表观遗传学可能的调控作用及机制进行综述。      

MicroRNA control of epithelial‐mesenchymal transition in cancer stem cells

Cancer stem cells (CSCs) represent a small subset of cancer cell populations that possess characteristics associated with normal stem cells. They have the ability to self‐renew, and are able to generate diverse tumor cells and account for metastases. Therefore, CSCs are widely accepted as potential mediators of therapeutic resistance and novel targets for anti‐cancer treatments. Recent progress has highlighted the significance of epithelial–mesenchymal transition (EMT) process in CSC formation, as well as the crucial role of microRNAs in controlling EMT and cancer metastasis. MicroRNAs are also reported to take part in the control of CSC functions and the regulation of cancer progression by affecting EMT process. Thus, it is highly crucial to develop deeper understanding of the mechanisms that how microRNAs control EMT processes and regulate CSC functions for better therapeutics of cancer disease. Herein we make this review to summarize the current understanding of the regulatory mechanisms of EMT in CSC initiation, with a special focus on the role of microRNAs in EMT control, and discuss the implications of targeting CSCs for cancer therapeutics.     

MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer

Background:

Side population (SP) cells and their relationship to stem cell-like properties have been insufficiently studied in colorectal cancer (CRC). MicroRNAs (miRNAs) have attracted much attention but their roles in the maintenance of SP phenotype remain unclear.

Methods:

The SPs from CRC cell lines and primary cell cultures were analysed for stem cell-like properties. MiRNA microarray analysis identified miR-328 as a potential stemness miRNA of SP phenotype. The level of miR-328 expression in clinical samples and its correlation with SP fraction were determined. Gain-of-function and loss-of-function studies were performed to examine its roles in cancer stem-like SP cells. Furthermore, bioinformatics prediction and experimental validation were used to identify miR-328 target genes.

Results:

The SP cells sorted from CRC possess cancer stem cell (CSC)-like properties, including self-renewal, differentiation, resistance to chemotherapy, invasive and strong tumour formation ability. MiR-328 expression was significantly reduced in SP cells compared with Non-SP cells (P<0.05). Moreover, miR-328 expression was downregulated in CRC (n=33, P<0.05) and low miR-328 expression tend to correlate with high SP fraction (n=15, r=0.6559, P<0.05, Pearson''s correlation). Functional studies indicated that miR-328 expression affects the number of SP cells. In addition, miR-328 overexpression reversed drug resistance and inhibited cell invasion of SP cells. Furthermore, luciferase reporter assay demonstrated that miR-328 directly targets ABCG2 and MMP16 and affects the levels of mRNA and protein expression in SP cells.

Conclusion:

These findings indicate that CRC contain cancer stem-like SP cells. MiR-328 has an important role in maintaining cancer stem-like SP phenotype that may be a potential target for effective CRC therapy.     

MicroRNA regulation of core apoptosis pathways in cancer

Recent research has demonstrated that microRNAs (miRNAs) are key regulators of many cell processes often deregulated in cancer, including apoptosis. Indeed, it is becoming clear that many miRNAs are anti-apoptotic and mediate this effect by targeting pro-apoptotic mRNAs or positive regulators of pro-apoptotic mRNAs. Conversely, many pro-apoptotic miRNAs target anti-apoptotic mRNAs or their positive regulators. We have reviewed the current knowledge in this area including evidence of miRNA involvement in cancer drug resistance.     

Dynamic regulation of cancer stem cells and clinical challenges

A small population of cancer cells referred to as cancer stem cells (CSCs) have received particular attention, as they have been revealed to acquire stem cell-like properties and become the main cause of tumor propagation, metastasis and drug resistance. The CSC theory of tumor formation was believed to follow the hierarchical model initially, and therefore many CSC-targeted therapy methods were expected to cure cancer by eradicating CSCs. However, subsequent CSC research has revealed that rather than a distinct entity, the CSC is a dynamic status that can be continually dedifferentiated from progenitor or differentiated cancer cells. Elucidation of this bidirectional transition mechanism would help perfect the CSC theory and be of great value in the development of more effective anti-cancer drugs. Here, we reviewed the mechanisms of reciprocal conversion between non-CSCs and CSCs. Moreover, several approaches of target CSCs and non-CSCs together with unbiased eradication of all cancer cells are also discussed.     

MicroRNA regulation and therapeutic targeting of survivin in cancer

Survivin, the smallest member of IAP (inhibitor of apoptosis) family, is a dual functional protein acting as a critical apoptosis inhibitor and key cell cycle regulator. Survivin is usually expressed in embryonic tissues during development and undetectable in most terminally differentiated tissues. Numerous studies demonstrate that survivin is selectively upregulated in almost all types of human malignancies and its overexpression positively correlates with poor prognosis, tumor recurrence, and therapeutic resistance. This differential expression of survivin in tumors and normal tissues draws a great interest to develop survivin-targeted therapy for cancer treatment. Nonetheless, the molecular mechanisms controlling survivin expression in malignant tumor cells have not been fully understood. While aberrant activation of receptor tyrosine kinases (RTKs) and the downstream signaling, such as PI-3K/Akt, MEK/MAPK, mTOR, and STAT pathways, have frequently been shown to upregulate survivin, recent data suggest that a class of noncoding RNAs, microRNAs (miRNAs) also play an important role in survivin dysregulation in human cancers. Here, we focus on survivin expression-regulated by specific miRNAs binding to the 3’-UTR of survivin mRNA, and summarize the latest advances on survivin-targeted therapy in clinical trials and the therapeutic potential of survivin-targeting miRNAs in cancer.     

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。     

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。     

上皮间质转化参与CSC生成及其调控

肿瘤组织中存在一小部分具有无限增殖、自我更新、分化潜能、放化疗耐受以及高致瘤能力等干细胞特性的肿瘤干细胞（cancer stem cells,CSC）,它们是肿瘤无法治愈并不断进展的重要原因。许多与诱导肿瘤细胞上皮间质转化（epithelial-to-mesenchymal transition,EMT）相关的信号通路与CSC 的生成及调控相关。本综述简要阐述了EMT 与CSC 生成及调控相关的研究进展。     

肺癌干细胞

现有研究表明,在肺癌中与干细胞功能相关的Wnt、Notch和Hedgehog信号通路被异常激活,它们与肺癌干细胞的高致瘤性、高转移性、耐药性等特性密切相关.多项研究显示肺癌干细胞群高度表达肿瘤耐药蛋白并且对放化疗明显耐受.因此,如何靶向治疗肺癌干细胞,最终根治肺癌,正逐渐成为肿瘤靶向治疗研究中的热点.