ceRNA在肿瘤中的研究进展

竞争性内源RNA(competing endogenous RNA,ceRNA)是一类能与miRNA结合位点（miRNA response element,MRE）结合从而抑制miRISC形成,并能进一步增加相应mRNA的表达来达到RNA间相互沟通及转录后调控基因表达的一类非编码RNA。ceRNA主要包括长链非编码RNA（long non-coding RNA,lncRNA）、环状RNA（circular RNA,circRNA）、假基因、人工合成miRNA抑制剂及病毒miRNA抑制剂等。目前越来越多的研究表明ceRNA在肿瘤的基因调控及肿瘤细胞增殖、凋亡、细胞周期、侵袭和转移等各种生物过程中发挥重要作用。本文从ceRNA分类、调控网络及ceRNA在不同肿瘤中的研究进展作一综述。     

Non-coding RNAs (miRNAs and lncRNAs) and their roles in lymphogenesis in all types of lymphomas and lymphoid malignancies

Contemporary developments in molecular biology have been combined with discoveries on the analysis of the role of all non-coding RNAs (ncRNAs) in human diseases, particularly in cancer, by examining their roles in cells. Currently, included among these common types of cancer, are all the lymphomas and lymphoid malignancies, which represent a diverse group of neoplasms and malignant disorders. Initial data suggest that non-coding RNAs, particularly long ncRNAs (lncRNAs), play key roles in oncogenesis and that lncRNA-mediated biology is an important key pathway to cancer progression. Other non-coding RNAs, termed microRNAs (miRNAs or miRs), are very promising cancer molecular biomarkers. They can be detected in tissues, cell lines, biopsy material and all biological fluids, such as blood. With the number of well-characterized cancer-related lncRNAs and miRNAs increasing, the study of the roles of non-coding RNAs in cancer is bringing forth new hypotheses of the biology of cancerous cells. For the first time, to the best of our knowledge, the present review provides an up-to-date summary of the recent literature referring to all diagnosed ncRNAs that mediate the pathogenesis of all types of lymphomas and lymphoid malignancies.     

长链非编码RNA作为ceRNA在胃癌上皮间质转化中的作用研究进展

胃癌是世界上最常见的恶性肿瘤之一.上皮间质转化(EMT)在胃癌的进展和转移中发挥着关键作用.EMT的调控是一个复杂的网络,转录因子SNAIL/SLUG、TWIST1/2、ZEB1/2在肿瘤EMT的过程中发挥着重要诱导作用,此外EMT的调控还与细胞因子、miRNAs(如miR-200家族)等的参与有关.近些年随着非编码R...     

MicroRNAs and long non-coding RNAs: prospects in diagnostics and therapy of cancer

Background

Non-coding RNAs (ncRNAs) are key regulatory molecules in cellular processes, and are potential biomarkers in many diseases. Currently, microRNAs and long non-coding RNAs are being pursued as diagnostic and prognostic biomarkers, and as therapeutic tools in cancer, since their expression profiling is able to distinguish different cancer types and classify their sub-types.

Conclusions

There are numerous studies confirming involvement of ncRNAs in cancer initiation, development and progression, but have only been recently identified as new diagnostic and prognostic tools. This can be beneficial in future medical cancer treatment options, since ncRNAs are natural antisense interactors included in regulation of many genes connected to survival and proliferation. Research is directed in development of useful markers for diagnosis and prognosis in cancer and in developing new RNA-based cancer therapies, of which some are already in clinical trials.     

Non-coding RNAs in DNA damage response

Genome-wide studies have revealed that human and other mammalian genomes are pervasively transcribed and produce thousands of regulatory non-protein-coding RNAs (ncRNAs), including miRNAs, siRNAs, piRNAs and long non-coding RNAs (lncRNAs). Emerging evidences suggest that these ncRNAs also play a pivotal role in genome integrity and stability via the regulation of DNA damage response (DDR). In this review, we discuss the recent finding on the interplay of ncRNAs with the canonical DDR signaling pathway, with a particular emphasis on miRNAs and lncRNAs. While the expression of ncRNAs is regulated in the DDR, the DDR is also subjected to regulation by those DNA damage-responsive ncRNAs. In addition, the roles of those Dicer- and Drosha-dependent small RNAs produced in the vicinity of double-strand breaks sites are also described.     

竞争性内源RNA与肿瘤病理机制

竞争性内源RNA(ceRNA)是一类RNA分子的统称,包括mRNA、假基因、长非编码RNA(lncRNA)、环状RNA(circRNA).ceRNA通过竞争性结合共同的微小RNA(miRNA)而削弱其对mRNA翻译的抑制作用.多项研究已证实ceRNA失调与乳腺癌、胃癌、淋巴瘤等肿瘤发生密切相关.随着ceRNA的研究深入,其或可作为肿瘤的临床诊断标志及治疗靶点.     

Non-coding RNAs deregulation in oral squamous cell carcinoma: advances and challenges

Oral squamous cell carcinoma (OSCC) is a common cause of cancer death. Despite decades of improvements in exploring new treatments and considerable advance in multimodality treatment, satisfactory curative rates have not yet been reached. The difficulty of early diagnosis and the high prevalence of metastasis associated with OSCC contribute to its dismal prognosis. In the last few decades the emerging data from both tumor biology and clinical trials led to growing interest in the research for predictive biomarkers. Non-coding RNAs (ncRNAs) are promising biomarkers. Among numerous kinds of ncRNAs, short ncRNAs, such as microRNAs (miRNAs), have been extensively investigated with regard to their biogenesis, function, and importance in carcinogenesis. In contrast to miRNAs, long non-coding RNAs (lncRNAs) are much less known concerning their functions in human cancers especially in OSCC. The present review highlighted the roles of miRNAs and newly discovered lncRNAs in oral tumorigenesis, metastasis, and their clinical implication.     

Regulatory RNAs,microRNA, long-non coding RNA and circular RNA roles in colorectal cancer stem cells

The properties of cancer stem cells (CSCs), such as self-renewal, drug resistance, and metastasis, have been indicated to be responsible for the poor prognosis of patients with colon cancers. The epigenetic regulatory network plays a crucial role in CSC properties. Regulatory non-coding RNA (ncRNA), including microRNAs, long noncoding RNAs, and circular RNAs, have an important influence on cell physiopathology. They modulate cells by regulating gene expression in different ways. This review discusses the basic characteristics and the physiological functions of colorectal cancer (CRC) stem cells. Elucidation of these ncRNAs will help us understand the pathological mechanism of CRC progression, and they could become a new target for cancer treatment.     

非编码RNA在喉鳞状细胞癌中的研究进展

非编码RNA是一类不编码蛋白质的RNA, 包括微小RNA(microRNA, miRNA)、长链非编码RNA(long non-coding RNA, lncRNA)和环状RNA(circular RNA, circRNA)等。非编码RNA不仅在生物调节过程中扮演着重要角色, 在包括肿瘤在内的多种疾病的发生机制中也起到了不可或缺的作用, 其在喉癌的诊断、预后评估及治疗中同样具有重要的临床价值。喉鳞状细胞癌是喉癌中最常见的病理学类型, 近年来发病率有明显增高的趋势, 已严重危害人类健康及生存质量。本文总结了近年国内外研究, 对miRNA、lncRNA和circRNA在喉癌发生发展的作用机制进行综述。      

Non-coding RNAs in cardiac regeneration

Developing new therapeutic strategies which could enhance cardiomyocyte regenerative capacity is of significant clinical importance. Though promising, methods to promote cardiac regeneration have had limited success due to the weak regenerative capacity of the adult mammalian heart. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs, miRs) and long non-coding RNAs (lncRNAs), are functional RNA molecules without a protein coding function that have been reported to engage in cardiac regeneration and repair. In light of current regenerative strategies, the regulatory effects of ncRNAs can be categorized as follows: cardiac proliferation, cardiac differentiation, cardiac survival and cardiac reprogramming. miR-590, miR-199a, miR-17-92 cluster, miR302-367 cluster and miR-222 have been reported to promote cardiomyocyte proliferation while miR-1 and miR-133 suppress that. miR-499 and miR-1 promote the differentiation of cardiac progenitors into cardiomyocyte while miR-133 and H19 inhibit that. miR-21, miR-24, miR-221, miR-199a and miR-155 improve cardiac survival while miR-34a, miR-1 and miR-320 exhibit opposite effects. miR-1, miR-133, miR-208 and miR-499 are capable of reprogramming fibroblasts to cardiomyocyte-like cells and miR-284, miR-302, miR-93, miR-106b and lncRNA-ST8SIA3 are able to enhace cardiac reprogramming. Exploring non-coding RNA-based methods to enhance cardiac regeneration would be instrumental for devising new effective therapies against cardiovascular diseases.     

Analyzing the interactions of mRNAs,miRNAs, lncRNAs and circRNAs to predict competing endogenous RNA networks in glioblastoma

Cross-talk between competitive endogenous RNAs (ceRNAs) may play a critical role in revealing potential mechanisms of tumor development and physiology. Glioblastoma is the most common type of malignant primary brain tumor, and the mechanisms of tumor genesis and development in glioblastoma are unclear. Here, to investigate the role of non-coding RNAs and the ceRNA network in glioblastoma, we performed paired-end RNA sequencing and microarray analyses to obtain the expression profiles of mRNAs, lncRNAs, circRNAs and miRNAs. We identified that the expression of 501 lncRNAs, 1999 mRNAs, 2038 circRNAs and 143 miRNAs were often altered between glioblastoma and matched normal brain tissue. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed on these differentially expressed mRNAs and miRNA-mediated target genes of lncRNAs and circRNAs. Furthermore, we used a multi-step computational framework and several bioinformatics methods to construct a ceRNA network combining mRNAs, miRNAs, lncRNAs and circRNA, based on co-expression analysis between the differentially expressed RNAs. We identified that plenty of lncRNAs, CircRNAs and their downstream target genes in the ceRNA network are related to glutamatergic synapse, suggesting that glutamate metabolism is involved in glioma biological functions. Our results will accelerate the understanding of tumorigenesis, cancer progression and even therapeutic targeting in glioblastoma.     

lncRNA MEG3作为miR-21的ceRNA在恶性肿瘤中的作用

长非编码RNA(lncRNA)-母系表达基因3(MEG3)和微小RNA-21(miR-21)是抑癌和致癌因子。竞争性内源RNA(ceRNA)假说为研究RNA之间的相互作用提供了新的策略。MEG3可作为miR-21的ceRNA在乳腺癌、宫颈癌、胃癌、肺癌、白血病等恶性肿瘤的发生、发展、增殖、转移以及药物耐药、预后中发挥重要作用。     

Non-coding RNA in drug resistance of gastric cancer

Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide. The poorly prognosis and survival of GC are due to diagnose in an advanced, non-curable stage and with a limited response to chemotherapy. The acquisition of drug resistance accounts for the majority of therapy failure of chemotherapy in GC patients. Although the mechanisms of anticancer drug resistance have been broadly studied, the regulation of these mechanisms has not been completely understood. Accumulating evidence has recently highlighted the role of non-coding RNAs (ncRNAs), including long non-coding RNAs and microRNAs, in the development and maintenance of drug resistance due to their regulatory features in specific genes involved in the chemoresistant phenotype of GC. We review the literature on ncRNAs in drug resistance of GC. This review summarizes the current knowledge about the ncRNAs’ characteristics, their regulation of the genes involved in chemoresistance and their potential as targeted therapies for personalized treatment in resistant GC.     

Recent advances in extracellular vesicles in gastrointestinal cancer and lymphoma

Extracellular vesicles (EVs) are intercellular communication agents that transfer microRNAs (miRNAs), other non-coding RNAs (ncRNAs), messenger RNAs (mRNAs), proteins, lipids, metabolites, and other molecules from donor cells (e.g., cancer cells) to recipient cells (e.g., stromal cells). In 2007, miRNAs were reported to be abundant among the ncRNAs present in EVs. Since then, many studies have investigated the functions of miRNAs and have attempted to apply these molecules to aid in the diagnosis and treatment of cancer. Research on EVs has expanded, particularly in the field of cancer, because cancer cells heavily secrete EVs. The cargo of these EVs, especially those in small EVs, such as exosomes, is assumed to work cooperatively and significantly in the tumor microenvironment and to promote metastasis. In this review, we first summarize recent studies on EVs in gastrointestinal cancer and highlight studies on human satellite II RNAs, which are a type of ncRNA found in EVs that possess repetitive sequences. Second, since several recent studies have revealed that phospholipids, which are components of EV membranes, play important roles in intercellular communication and the generation of lipid mediators in the tumor microenvironment, we review the reported roles of these molecules and discuss their potential use in the design of new cancer treatments.     

Exosomal Non-Coding RNAs: New Insights into the Biology of Hepatocellular Carcinoma

Exosomes, extracellular vesicles with a diameter of 40 to 160 nm, are among the smallest extracellular vesicles released by cells. They deliver different cargoes, including proteins, DNAs, and RNAs, and facilitate communication between cells to coordinate a variety of physiological and pathological functions. Hepatocellular carcinoma (HCC) is the sixth common malignant tumor and the fourth leading cause of cancer-related death worldwide. Its molecular mechanism remains largely unknown, and there is a lack of reliable and noninvasive biomarkers for early diagnosis and prognosis prediction. Mounting evidence has shown that exosomes carry a variety of ncRNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), which play critical roles in the occurrence and progression of HCC. In this review, we summarize the recent findings of exosomal miRNAs, lncRNAs, and circRNAs in HCC from their impact on the development of HCC to their potential applications in the diagnosis and treatment of HCC.