microRNA对肺癌化疗耐药性影响的研究进展

化疗耐药性是肺癌治疗的主要挑战之一,导致许多患者的化疗方案无效,并延误了接受合适治疗的时机。因此,研究肺癌化疗耐药性的机制是至关重要的。microRNA (miRNA)作为小分子片段RNA,参与了许多生命过程的调节,并在细胞耐药性产生过程中发挥重要的作用。研究表明,在化疗过程中,miRNAs可以通过降低多种药物耐药性相关基因的表达或促进细胞逃逸凋亡,参与耐药性的调节。然而,对于miRNAs介导的化疗耐药性产生机制的研究还不完善。现有研究表明,特定miRNAs的改变可能与多种癌症的获得性耐药相关,并调节肺癌细胞对化疗药物的敏感性。对miRNAs在肺癌耐药性中的作用及研究进展进行系统阐述。     

微小RNA与肺癌耐药

肺癌细胞对化疗药物产生耐药性是目前肺癌化疗过程中遇到的主要问题。微小RNA（miRNA）是一类内源性非编码短链小分子RNA,它能调节细胞生长、凋亡和信号转导。miRNA的多态性与药物代谢和耐药形成密切相关,异常表达的miRNA对预测肺癌化疗药物敏感性有重要作用。调节特异miRNA的表达,将为克服肺癌耐药和选择个体化治疗开辟新的途径。     

miRNA表达谱与上皮性卵巢癌

Micro RNA(miRNA)是近年来研究发现的一种高度保守,长度大约19-25个核苷酸的非编码小分子RNA,起着调控基因表达的作用。目前认为miRNA能调控细胞周期、凋亡、分化、发育和新陈代谢等,参与肿瘤的发生与发展,因此异常表达的miRNAs表达谱有可能成为一种全新的肿瘤分子标记物。相关研究表明,miRNA能够以一种被保护的状态存在于血清及血浆中,因此miRNA表达谱的发现具有易检测性、重现性以及非侵袭性。研究显示血清及血浆中miRNA表达谱可作为上皮性卵巢癌生物信号分子,在上皮性卵巢癌早期诊断、预后判断和化疗药物应用等方面具有不可替代的作用。本文将对miRNA表达谱与上皮性卵巢癌的关系进行一个简单总结。     

MicroRNA对胃癌调控作用的研究进展

微小RNA(microRNA, miRNA)是一类源于真核生物自身基因组的非编码小RNA,参与了肿瘤发生的多个阶段,通过直接靶向抑制其下游靶mRNA的表达或利用其竞争性内源RNA(如lncRNA)间接调控靶基因的表达,在癌症进程中发挥促癌或抑癌作用。胃癌是一种常见的高发病率、高转移率、高侵袭率和高死亡率的恶性肿瘤,大量研究表明,胃癌细胞的恶性生物学行为、表观遗传学改变和化疗耐药性等均与miRNAs的异常表达密切相关。特别注意的是,外泌体源性miRNAs通过外泌体的包装及运载,在细胞之间或细胞与微环境之间传递,也是胃癌进展中必不可少的一环。本文重点概述了miRNAs通过不同信号通路及调控机制在胃癌恶性增殖、凋亡、侵袭、转移、DNA甲基化和化疗耐药等方面的作用,针对miRNAs作用机制的研究可能为胃癌的诊断与治疗提供新见解。     

miRNA与肿瘤细胞耐药的关系

化学药物治疗（简称化疗）是目前治疗恶性肿瘤的主要手段之一,但化学治疗同时受到原发性耐药和获得性耐药的制约.细胞学上的耐药机制包括药物外排泵,如P-糖蛋白和多药耐药相关蛋白的过表达、药物靶点的突变、细胞修复系统的增强及细胞凋亡的减弱等.这些途径中的关键基因在遗传学水平及表观遗传水平的变异可以导致肿瘤细胞耐药现象的发生.其中,miRNA是这些关键基因的调节方式之一.miRNA参与生命过程中一系列的重要过程,包括动物的生长发育、组织分化和疾病的发生发展等,也参与调节肿瘤细胞对化疗药物的敏感性.本文简要综述了miRNA与肿瘤细胞耐药性的相关进展.     

细胞凋亡抑制蛋白cIAP 与卵巢癌耐药性的研究进展

卵巢恶性肿瘤是女性生殖系统三大恶性肿瘤之一,其发病率在女性生殖系统肿瘤中占第三位,而死亡率却高居首位。目前对于晚期卵巢癌(Ⅲ或Ⅳ期)多倾向于用新辅助化疗+肿瘤细胞减灭术+术后周期性化疗的治疗方法。但是,尽管多数患者在最初对化疗药物较敏感,但仍有60%~80%最终死于卵巢癌,这些患者大部分都对化疗药物产生了耐药性,在更换新的化疗方案初期是有效的,但最终仍会耐药。近年来,有关细胞凋亡抑制蛋白(cIAP,cellular inhibitors of apoptosis proteins)在卵巢癌复发耐药中的作用机制的研究越来越受到重视。研究证实,cIAP在耐药肿瘤细胞中呈高表达,并与多种因子共同参与形成了上皮性卵巢癌的耐药机制,抑制了化疗药物引起的肿瘤细胞的凋亡。这些发现为攻克卵巢癌的耐药机制提供了重要线索,也为卵巢癌化疗药物的应用指出了新的方向。     

siRNA与miRNA在生物基因调控中的沉默机制比较

siRNA和miRNA的沉默机制是生物基因调控的重要手段之一. 小干扰RNA（small interfering RNA,siRNA）是RNA干扰的引发物,激发与之互补的目标mRNA沉默. 非编码RNA中的微小RNA（microRNA,miRNA）,能够识别特定的目标mRNA,通过与mRNAs的3′ 非翻译区结合,影响该目标蛋白的翻译水平. siRNA和miRNA的基因调控机制对生物学研究及疾病的病因和治疗等有直接影响. 本文主要对siRNAs和miRNAs的生物起源及沉默机制进行比较性论述：提出Dicers酶蛋白、Ago蛋白以及20 nt~25 nt的双链RNAs的 3类大分子是RNA沉默的特征结构,并进行了说明性论述|总结性叙述了siRNA和miRNA的2类小分子经典沉默机制,并提出其异同点. 最后,本文根据近期研究进展,对siRNA和miRNA的生物起源及沉默机制提出了新的疑问.     

siRNA与miRNA在生物体基因调控中沉默机制的比较

siRNA和miRNA的沉默机制是生物基因调控的重要手段之一.小干扰RNA(small interfering RNA,siRNA)是RNA干扰的引发物,激发与之互补的目标mRNA沉默.非编码RNA中的微小RNA(microRNA,miRNA),能够识别特定的目标mRNA,通过与mRNAs的3'非翻译区结合,影响该目标蛋白的翻译水平.siRNA和miRNA的基因调控机制对生物学研究及疾病的病因和治疗等有直接影响.本文主要对siRNAs和miRNAs的生物起源及沉默机制进行比较性论述:提出Dicers酶蛋白、Ago蛋白以及20 nt～25 nt的双链RNAs的3类大分子是RNA沉默的特征结构,并进行了说明性论述;总结性叙述了siRNA和miRNA的2类小分子经典沉默机制,并提出其异同点.最后,本文根据近期研究进展,对siRNA和miRNA的生物起源及沉默机制提出了新的疑问.     

微RNA在卵巢上皮性癌发生发展中作用及其临床意义

研究表明,miRNA参与了胚胎发育、损伤修复、糖尿病、心脏病等许多重要生理病理过程,特别是在恶性肿瘤的发生发展中发挥了重要作用,并具有潜在的临床意义。本文比较详细地叙述了有关miRNA的重要基础研究成果,并就miRNA在卵巢癌组织及细胞中的表达、miRNA在卵巢癌发生发展中的作用、miRNA与卵巢癌早期诊断、化疗耐药及预后判断等方面的最新研究成果进行了综述。     

共生菌与卵巢癌相关研究进展CSCD

卵巢癌是女性生殖系统常见的恶性肿瘤之一,病死率居女性生殖系统恶性肿瘤之首。卵巢癌治疗后的复发和耐药是临床难以攻克的关键问题。近年来,多项研究发现体内共生菌的变化和卵巢癌的发生发展密切相关。女性内生殖器和肠道共生菌的改变可能导致卵巢癌的易感性或发展,而卵巢癌的进展又可能反过来影响内生殖器各部位菌群的组成。另外,共生菌对卵巢癌相关化疗药物的抗肿瘤疗效也有重要影响。一方面,部分共生菌与化疗药物联合使用,可增强药物的疗效;另一方面,共生菌的存在可能促进肿瘤的耐药。本文就女性内生殖器和共生菌的改变与卵巢癌的关系以及共生菌对卵巢癌相关化疗药物抗肿瘤疗效的影响进行综述,以期对卵巢癌的筛查、治疗和预防提供新的思路。     

MicroRNAs: key players of taxane resistance and their therapeutic potential in human cancers

The successful long‐term use of taxane for cancer therapy is often prevented by the development of drug resistance in clinic. Thus, exploring the mechanisms involved is a first step towards rational strategies to overcome taxane resistance. Taxane resistance‐related microRNA (miRNAs) are under investigation and miRNAs could induce the taxane resistance of tumour cells by regulating cell cycle distribution, survival and/or apoptosis pathways, drug transports, epithelial–mesenchymal transition and cancer stem cell. This article summarizes current research involving miRNAs as regulators of key target genes for tanxanxe chemoresistance and discusses the complex regulatory networks of miRNAs. Also, the authors will envisage future developments towards the potential use of targeting miRNAs as a novel strategy for improving response of tumour patients to taxane. miRNAs play critical roles in taxane chemoresistance and the miRNA‐based therapies will be helpful for overcoming drug resistance and developing more effective personalized anti‐cancer treatment strategies. Further research studies should be performed to promote therapeutic–clinical use of taxane resistance‐related miRNAs in cancer patients, especially in those patients with taxane‐resistant cancers.     

MicroRNAs and drug modulation in cancer: an intertwined new story

MicroRNAs (miRNAs) are endogenous small non-coding RNAs (ncRNAs) which play important regulatory roles in physiological processes such as cellular differentiation, proliferation, development, apoptosis and stem cell self-renewal. An increasing number of papers have clearly claimed their involvement in cancer, providing, in some cases, also the molecular mechanisms implicated. Several studies led to the conclusion that miRNAs can be effectively used as anticancer agents alone or in combination with existing anticancer drugs. In particular, miRNAs can be effectively used to overcome drug resistance, one of the main factors responsible for anticancer treatment insuccess. One of the main questions remains how to modulate the expression of miRNAs in cancer cells. Interestingly, a few studies have shown that the expression of miRNAs is affected by drugs (including some drugs currently used as anticancer agents), therefore providing the rationale for an intertwined scenario in which miRNAs can be modulated by drugs and, in turn, can affect drug sensitivity of cancer cells.     

Drug resistance‐related microRNAs in osteosarcoma: Translating basic evidence into therapeutic strategies

Although the application of multiple chemotherapy brought revolutionary changes to improve overall survival of osteosarcoma patients, the existence of multidrug resistance (MDR) has become a great challenge for successful osteosarcoma treatment in recent decades. Substantial studies have revealed various underlying mechanisms of MDR in cancers. As for osteosarcoma, evidence has highlighted that microRNAs (miRNAs) can mediate in the processes of DNA damage response, apoptosis avoidance, autophagy induction, activation of cancer stem cells, and signal transduction. Besides, these drug resistance‐related miRNAs showed much promise for serving as candidates for predictive biomarkers of poor outcomes and shorter survival time, and therapeutic targets to reverse drug resistance and overcome treatment refractoriness. This review aims to demonstrate the potential molecular mechanisms of miRNAs‐regulated drug resistance in osteosarcoma, and provide insight in translating basic evidence into therapeutic strategies.     

The role of miR-34 in cancer drug resistance

Resistance to conventional chemotherapy remains a major cause of cancer relapse and cancer-related deaths. Therefore, there is an urgent need to overcome resistance barriers. To improve cancer treatment approaches, it is critical to elucidate the basic mechanisms underlying drug resistance. Increasingly, the mechanisms involving micro-RNAs (miRNAs) are studied because miRNAs are also considered practical therapeutic options due to high degrees of specificity, efficacy, and accuracy, as well as their ability to target multiple genes at the same time. Years of research have firmly established miR-34 as a key tumor suppressor miRNA whose target genes are involved in drug resistance mechanisms. Indeed, numerous articles show that low levels of circulating miR-34 or tumor-specific miR-34 expression are associated with poor response to chemotherapy. In addition, elevation of inherently low miR-34 levels in resistant cancer cells effectively restores sensitivity to chemotherapeutic agents. Here, we review this literature, also highlighting some contradictory observations. In addition, we discuss the potential utility of miR-34 expression as a predictive biomarker for chemotherapeutic drug response. Although caution needs to be exercised, miR-34 is emerging as a biomarker that could improve cancer precision medicine.     

Drug Resistance in Glioblastoma: A Mini Review

Glioblastoma multiforme (GBM) is recognized as the most common and lethal form of central nervous system cancer. Currently used surgical techniques, chemotherapeutic agents, and radiotherapy strategies have done very little in extending the life expectancies of patients diagnosed with GBM. The difficulty in treating this malignant disease lies both in its inherent complexity and numerous mechanisms of drug resistance. In this review, we summarize several of the primary mechanisms of drug resistance. We reviewed available published literature in the English language regarding drug resistance in glioblastoma. The reasons for drug resistance in glioblastoma include drug efflux, hypoxic areas of tumor cells, cancer stem cells, DNA damage repair, and miRNAs. Many potential therapies target these mechanisms, including a series of investigated alternative and plant-derived agents. Future research and clinical trials in glioblastoma patients should pursue combination of therapies to help combat drug resistance. The emerging new data on the potential of plant-derived therapeutics should also be closely considered and further investigated.     

MicroRNAs in cancer drug resistance: Basic evidence and clinical applications

Development of drug resistance has considerably limited the efficacy of cancer treatments, including chemotherapy and targeted therapies. Hence, understanding the molecular mechanisms underpinning the innate or the acquired resistance to these therapies is critical to improve drug efficiency and clinical outcomes. Several studies have implicated microRNAs (miRNA) in this process. MiRNAs repress gene expression by specific binding to complementary sequences in the 3' region of target messenger RNAs (mRNAs), followed by target mRNA degradation or blocked translation. By targeting molecules specific to a particular pathway within tumor cells, the new generation of cancer treatment strategies has shown significant advantages over conventional chemotherapy. However, the long-term efficacy of targeted therapies often remains poor, because tumor cells develop resistance to such therapeutics. Targeted therapies often involve monoclonal antibodies (mAbs), such as those blocking the ErB/HER tyrosine kinases, epidermal growth factor receptor (cetuximab) and HER2 (trastuzumab), and those inhibiting vascular endothelial growth factor receptor signaling (e.g., bevacizumab). Even though these are among the most used agents in tumor medicine, clinical response to these drugs is reduced due to the emergence of drug resistance as a result of toxic effects in the tumor microenvironment. Research on different types of human cancers has revealed that aberrant expression of miRNAs promotes resistance to the aforementioned drugs. In this study, we review the mechanisms of tumor cell resistance to mAb therapies and the role of miRNAs therein. Emerging treatment strategies combine therapies using innovative miRNA mimics or antagonizers with conventional approaches to maximize outcomes of patients with cancer.     

MiR-130a and MiR-374a Function as Novel Regulators of Cisplatin Resistance in Human Ovarian Cancer A2780 Cells

Chemoresistance remains a major obstacle to effective treatment in patients with ovarian cancer, and recently increasing evidences suggest that miRNAs are involved in drug-resistance. In this study, we investigated the role of miRNAs in regulating cisplatin resistance in ovarian cancer cell line and analyzed their possible mechanisms. We profiled miRNAs differentially expressed in cisplatin-resistant human ovarian cancer cell line A2780/DDP compared with parental A2780 cells using microarray. Four abnormally expressed miRNAs were selected (miR-146a,-130a, -374a and miR-182) for further studies. Their expression were verified by qRT-PCR. MiRNA mimics or inhibitor were transfected into A2780 and A2780/DDP cells and then drug sensitivity was analyzed by MTS array. RT-PCR and Western blot were carried out to examine the alteration of MDR1, PTEN gene expression. A total of 32 miRNAs were found to be differentially expressed in A2780/DDP cells. Among them, miR-146a was down-regulated and miR-130a,-374a,-182 were upregulated in A2780/DDP cells, which was verified by RT-PCR. MiR-130a and miR-374a mimics decreased the sensitivity of A2780 cells to cisplatin, reversely, their inhibitors could resensitize A2780/DDP cells. Furthermore, overexpression of miR-130a could increase the MDR1 mRNA and P-gp levels in A2780 and A2780/DDP cells, whereas knockdown of miR-130a could inhibit MDR1 gene expression and upregulate the PTEN protein expression .In a conclusion, the deregulation of miR-374a and miR-130a may be involved in the development and regulation of cisplatin resistance in ovarian cancer cells. This role of miR-130a may be achieved by regulating the MDR1 and PTEN gene expression.     

Role of exosomal microRNAs in lung cancer biology and clinical applications

Exosomes, small extracellular vesicles ranging from 30 to 150 nm, are secreted by various cell types, including tumour cells. Recently, microRNAs (miRNAs) were identified to be encapsulated and hence protected from degradation within exosomes. These exosomal miRNAs can be horizontally transferred to target cells, in which they subsequently modulate biological processes. Increasing evidence indicates that exosomal miRNAs play a critical role in modifying the microenvironment of lung cancers, possibly facilitating progression, invasion, angiogenesis, metastasis and drug resistance. In this review, we summarize the novel findings on exosomal miRNA functions during lung cancer initiation and progression. In addition, we highlight their potential role and challenges as biomarkers in lung cancer diagnosis, prognosis and drug resistance and as therapeutic agents.