微小RNA在胃癌中的研究现状

微小RNA(miRNA)与胃癌具有密切关系。根据miRNA对胃癌促进和抑制的不同作用,可将miRNA分为癌基因和抑癌基因。由于miRNA在胃癌和健康人群中表达具有差异,因此可成为新型的肿瘤标志物进行胃癌辅助诊断和预测治疗反应及预后。掌握miRNA与胃癌耐药的关系,有利于研发新的治疗方式。本文将从miRNA与胃癌的发生发展、诊断、预后、耐药、治疗等方面进行综述。     

miRNA对骨质疏松症的调控

MicroRNA（miRNA）是一种内源性的单链非编码小RNA。通过与靶mRNA的3’UTR结合,参与调控约30%的基因表达,是重要的转录后水平调控因子。在细胞的增值、分化、凋亡、代谢等生理过程中发挥广泛的作用。研究表明,miRNA与肿瘤、心脏病、糖尿病、帕金森综合症等多种复杂疾病的发生有关,且与多药耐药有关,本文将就miRNA对骨质疏松症的调控等作一综述。     

miRNA 在卵巢癌中作用的研究进展

卵巢癌是目前死亡率最高且预后最差的妇科恶性肿瘤,缺乏有效的早期诊断方法以及化疗耐药是其主要原因。微小RNA（miRNA）是一种内源性的非编码短序列小RNA,主要通过在转录后水平降解靶mRNA或者抑制靶基因的表达而参与调控细胞的生长、增殖和凋亡等。一些miRNA 可以通过调节体内多种癌基因和抑癌基因的表达,参与卵巢癌的发生、浸润及转移等进程;且多种特征性miRNA 在个体内的差异性表达也与卵巢癌的耐药及预后密切相关。研究与卵巢癌相关的miRNA 的作用靶基因及其信号调控通路可为进一步提高卵巢癌的临床诊断与治疗提供新思路。本文主要就miRNA 在卵巢癌中作用的研究进展进行综述。     

肿瘤干细胞miRNA及miRNA作为肿瘤标志物的研究和临床应用进展

肿瘤干细胞(CSCs)理论为肿瘤的研究开辟了一个新的方向,CSCs学说认为肿瘤细胞具有异质性,肿瘤中存在干细胞样细胞,该群细胞是一种增殖失控、可形成肿瘤的细胞,只占肿瘤细胞很少部分,具有干细胞特性,是形成不同分化程度肿瘤细胞和肿瘤增长、复发及转移的根源。微小核糖核酸(miRNA)是广泛存在的非编码小RNA,调节着人类1/3的基因,越来越多的证据显示miRNA在肿瘤的发生发展中起着重要的作用,作为重要的转录后调控因子,广泛参与肿瘤相关基因调控的生物程序,使不同类型的肿瘤表现出特异的miRNA表达谱。近年来,CSCs的miRNA研究日益成为热点,已经发现多种CSCs中存在特异性表达的miRNA,对CSCs的生物学行为有了更进一步的认识。有研究发现肿瘤患者血浆中表达某些特异的miRNA,这些miRNA可以作为肿瘤的标志物对患者的病情及预后进行预测和判断。本文就近来CSCs中miRNA研究进展及miRNA作为肿瘤标志物研究进展进行综述。     

MicroRNA与鼻咽癌的关系

鼻咽癌（nasopharyngeal carcinoma,NPC）为我国常见的肿瘤,由多种致癌因素共同作用导致。MicroRNA(miRNA)是一种长度为19～25 nt的非编码RNA分子,可水平调控基因的表达。现有许多研究表明miRNA与鼻咽癌的发生发展有密切联系。本文就miRNA与鼻咽癌增殖、侵袭迁移、凋亡以及肿瘤微环境的关系作一综述,为鼻咽癌的治疗提供更多方向。     

miRNA在鼻咽癌中的研究进展

鼻咽癌是中国常见的恶性肿瘤之一，其发病位置隐蔽且在早期临床不容易发现，发现时大多数已经是中晚期。微小核糖核酸（miRNA）是一段长约为22个核苷酸的内源性非编码单链RNA分子。miRNA可以靶向调控多种肿瘤相关基因的表达。随着国内外对miRNA深入研究，肿瘤特异性miRNA成为治疗鼻咽癌的新靶点和预测预后的生物标志物。本文主要从分子生物学特性来综述miRNA在鼻咽癌发生、发展、诊治和预后评估、放疗耐药中的研究现状。     

血液系统肿瘤多药耐药研究进展

多药耐药是血液肿瘤化疗失败的重要原因，其发生是多种因素共同作用的结果。多药耐药基因1型（MDR1基因）单独或与其它耐药蛋白联合表达是血液系统肿瘤耐药的主要原因，此外，还有酶介导（TOPOⅡ，GST等）、凋亡调控基因介导多药耐药等机制。     

microRNA与肿瘤发生相关性的研究进展

microRNA(miRNA)是一种非编码的单链小分子RNA,广泛存在于真核生物中.它通过在转录后水平负调控基因的表达,参与生命过程中的一系列重要进程.近来研究发现,miRNA可能通过调控某些致癌基因和抑癌基因,参与肿瘤的发生和发展.因此,通过寻找与肿瘤相关的miRNA,可以为肿瘤的诊断和生物治疗提供新的靶标.     

低氧诱导因子-1α对细胞信号、细胞凋亡的影响及研究进展

低氧诱导因子-1（hypoxia—induciblefactor-1，HIF-1）是普遍存在于人和哺乳动物细胞内的缺氧应答调控因子，通过调控一系列与缺氧适应有关基因的表达以保持机体的氧稳态。HIF-1（尤其是HIF-1α）的表达水平与糖酵解、细胞周期阻滞、细胞生存与增殖、血管新生、血管舒缩、红细胞生成、肿瘤生长和转移以及肿瘤多药耐药等许多生命活动密切相关。多数肿瘤具有缺氧的微环境。HIF-1α对于肿瘤的效应是多方面的：HIF-1α在上游调控诸多与肿瘤发生密切相关的基因；肿瘤在低氧条件下选择更恶性的表型；增加细胞突变率；增加与血管新生和肿瘤侵袭有关的基因表达；低氧条件下细胞更具有耐药倾向。因此HIF-1α已经成为一个治疗肿瘤的新的关键性靶点。细胞信号、细胞凋亡在多细胞生物的个体发育、自稳平衡等生理以及肿瘤、炎症等病理过程中具有重要意义，理解HIF-1α对于细胞信号、细胞凋亡的调节，对于开发特异性的肿瘤治疗有着现实意义。现就HIF-1α对细胞信号、细胞凋亡的影响及研究进展作一综述。     

与结直肠癌转移相关的微小RNA研究现状北大核心CSCD

瘤转移是结直肠癌患者死亡的主要原因之一。microRNA(miRNA)对结直肠癌转移的作用包括调节肿瘤细胞上皮-间质转化、调控癌基因、抑癌基因以及肿瘤转移相关基因的表达等,通过与靶基因mRNA互补位点结合,在转录后水平调控靶基因的表达,进而调控肿瘤的发生、发展。近年来,越来越多的研究显示,miRNA在结直肠癌的侵袭转移中起重要的作用,有望成为结直肠癌治疗的新靶点。     

Molecular mechanisms and theranostic potential of miRNAs in drug resistance of gastric cancer

Introduction: Systemic chemotherapy is a curative approach to inhibit gastric cancer cells proliferation. Despite the great progress in anti-cancer treatment achieved during the last decades, drug resistance and treatment refractoriness still extensively persists. Recently, accumulating studies have highlighted the role of miRNAs in drug resistance of gastric cancers by modulating some drug resistance-related proteins and genes expression. Pre-clinical reports indicate that miRNAs might serve as ideal biomarkers and potential targets, thus holding great promise for developing targeted therapy and personalized treatment for the patients with gastric cancer.

Areas covered: This review provide a comprehensive overview of the current advances of miRNAs and molecular mechanisms underlying miRNA-mediated drug resistance in gastric cancer. We particularly focus on the potential values of drug resistance-related miRNAs as biomarkers and novel targets in gastric cancer therapy and envisage the future research developments of these miRNAs and challenges in translating the new findings into clinical applications.

Expert opinion: Although the concrete mechanisms of miRNAs in drug resistance of gastric cancer have not been fully clarified, miRNA may be a promising theranostic approach. Further studies are still needed to facilitate the clinical applications of miRNAs in drug resistant gastric cancer.     

A microarray based expression profiling of paclitaxel and vincristine resistant MCF-7 cells

Resistance to the broad spectrum of chemotherapeutic agents in cancer cell lines and tumors has been called multiple drug resistance (MDR). In this study, the molecular mechanisms of resistance to two anticancer agents (paclitaxel and vincristine) in mammary carcinoma cell line MCF-7 were investigated. Drug resistant sublines to paclitaxel (MCF-7/Pac) and vincristine (MCF-7/Vinc) that were developed from sensitive MCF-7 cells (MCF-7/S) were used. cDNA microarray analysis was performed for the RNA samples of sensitive and resistant cells in duplicate experiments. GeneSpring GX 7.3.1 Software was used in data analysis. The results indicated that the upregulation of MDR1 gene is the dominating mechanism of the paclitaxel and vincristine drug resistance. Additionally the upregulation of the genes encoding the detoxifying enzymes (i.e. GSTP1) was observed. Significant downregulation of apoptotic genes (i.e. PDCD2/4/6/8) and upregulation of some cell cycle regulatory genes (CDKN2A, CCNA2 etc.) was seen which may be in close relation to MDR in breast cancer. Drug resistant cancer cells exhibit different gene expression patterns depending on drug treatment, and each drug resistance phenotype is probably genetically different. Further functional studies are needed to demonstrate the complete set of genes contributing to the drug resistance phenotype in breast cancer cells.     

MiR-497对人胃癌细胞株顺铂耐药性的影响和机制

目的:通过建立人胃癌细胞SGC-7901的顺铂耐药细胞株SGC-7901/DDP,探讨miR-497对SGC-7901/DDP耐药性的影响及其机制。方法:体外研究采用顺铂体外逐步加量诱导法建立人胃癌细胞SGC-7901耐药株,并通过检测药物半抑制浓度和耐药基因MDR1、BCRP、MRP1的表达以鉴定耐药细胞株;检测在亲本及耐药细胞中miR-497、MDR1、MRP1、BCRP和凋亡相关基因Bax、Bcl-2的表达水平;miR-497模拟物分别转染SGC-7901/DDP细胞株,利用SRB法和流式细胞术检测转染miR-497模拟物后细胞对顺铂醇的敏感程度和细胞的周期、凋亡的变化,并检测耐药基因和凋亡相关基因的表达。结果:成功建立人胃癌SGC-7901/DDP耐药细胞株,耐药细胞株中耐药基因MDR1、BCRP、MRP1表达均升高,抗凋亡基因Bcl-2升高,凋亡基因Bax下降,miR-497表达下降(P<0.05);miR-497模拟物提高耐药细胞株对顺铂的药物敏感性,凋亡水平增加,细胞周期G₀/G₁期细胞增多(P<0.05),并可抑制耐药细胞中耐药基因的表达,降低Bcl-2/Bax比值(P<0.05)。结论:人胃癌耐药细胞株SGC-7901/DDP的miR-497表达下调;上调miR-497的表达可逆转人胃癌SGC-7901/DDP细胞株对化疗药物顺铂的耐药性。     

Identification of the collagen family as prognostic biomarkers and immune-associated targets in gastric cancer

BackgroundGastric cancer has extremely high morbidity and mortality. Currently, it is lack of effective biomarkers and therapeutic targets for guiding clinical treatment. In this study, we aimed to identify novel biomarkers and therapeutic targets for gastric cancer.MethodsDifferentially expressed genes (DEGs) between gastric cancer and normal tissues were obtained from Gene Expression Omnibus (GEO). Core genes were identified by constructing protein-protein interaction network of DEGs. The expression of core genes was verified in Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN and clinical samples. Further, the mutation, DNA methylation, prognostic value, and immune infiltration of core genes were validated by cBioPortal, MethSurv, Kaplan-Meier plotter, and Tumor Immune Estimation Resource (TIMER) databases. Additionally, drug response analysis was performed by Cancer Therapy Response Portal (CTRP).ResultsA total of seven collagen family members were identified as core genes among upregulated genes. And copy number amplification may be involved in the upregulation of COL1A1 and COL1A2. Importantly, the collagen family was associated with the poor prognosis of patients with metastasis. Among them, COL1A1 had a higher hazard ratio (HR) for overall survival than other members (HR = 2.33). The correlation between DNA methylation levels at CpG sites of collagen family members and the prognosis was verified in gastric cancer. Besides, collagen family expression was positively correlated with macrophages infiltration and the expression of M2 macrophages markers. Further, collagen expression was related to the sensitivity and resistance of gastric cancer cell lines to certain drugs.ConclusionsThe collagen family, especially COL1A1, COL1A2, and COL12A1, may act as potential prognostic biomarkers and immune-associated therapeutic targets in gastric cancer.     

青藤碱抑制类风湿关节炎骨破坏的研究进展

类风湿关节炎(RA)骨破坏伴随其整个病程,一旦骨破坏发生,则意味着其病理改变进入不可逆期。因此延缓甚至阻断骨破坏成为治疗RA的主要策略之一,具有十分重要的意义。青藤碱(SIN)是青风藤中提取的生物碱单体,具有良好的抗炎、镇痛、免疫抑制等药理作用,临床用于治疗类风湿关节炎取得良好疗效。该文主要将近年来有关SIN在RA骨破坏方面的研究作一详细阐述,以期为后续的临床研究提供理论依据。     

Overcoming drug resistance in pancreatic cancer

Introduction: Pancreatic cancer has the worst survival rate of all cancers. The current standard care for metastatic pancreatic cancer is gemcitabine, however, the success of this treatment is poor and overall survival has not improved for decades. Drug resistance (both intrinsic and acquired) is thought to be a major reason for the limited benefit of most pancreatic cancer therapies.

Areas covered: Previous studies have indicated various mechanisms of drug resistance in pancreatic cancer, including changes in individual genes or signaling pathways, the influence of the tumor microenvironment, and the presence of highly resistant stem cells. This review summarizes recent advances in the mechanisms of drug resistance in pancreatic cancer and potential strategies to overcome this.

Expert opinion: Increasing drug delivery efficiency and decreasing drug resistance is the current aim in pancreatic cancer treatment, and will also benefit the treatment of other cancers. Understanding the molecular and cellular basis of drug resistance in pancreatic cancer will lead to the development of novel therapeutic strategies with the potential to sensitize pancreatic cancer to chemotherapy, and to increase the efficacy of current treatments in a wide variety of human cancers.     

胃癌新辅助化疗耐药机制及治疗策略研究

目的 利用生物信息学筛选影响胃癌化疗耐药的特征基因,深入探讨化疗耐药的分子机制,为胃癌的化疗提供新策略。方法 在GEO数据库筛选胃癌DCS方案（多西他赛+顺铂+替吉奥）耐药表达谱芯片,利用GEO2R工具筛选胃癌耐药组织特征基因;构建差异基因的蛋白质-蛋白质相互作用（protein-protein interaction,PPI）网络;并分析PPI网络的关键节点和稳定模块,进而对差异基因和关键节点及模块基因进行功能富集及注释;再对差异基因进行化合物靶点模拟,筛选出潜在药物。结果 筛得胃癌化疗耐药差异基因共609个,构建PPI网络的关键节点为ACLY和AKT1。差异基因GO功能富集与KEGG通路富集结果显示,主要集中在免疫及肿瘤生长相关通路。C-MAP分析结果提示7个候选化合物吻合度评分>0.9。结论 本研究利用生物信息学筛选了影响胃癌化疗耐药的特征基因,深入探讨化疗耐药的分子机制,为胃癌的化疗提供了新策略。