Circular RNA in colorectal cancer

Circular RNA (circRNA) is a highly abundant type of single-stranded non-coding RNA. Novel research has discovered many roles of circRNA in colorectal cancer (CRC) including proliferation, metastasis and apoptosis. Furthermore, circRNAs also play a role in the development of drug resistance and have unique associations with tumour size, staging and overall survival in CRC that lend circRNAs the potential to serve as diagnostic and prognostic biomarkers. Among cancers worldwide, CRC ranks second in mortality and third in incidence. In order to have a better understanding of the influence of circRNA on CRC development and progression, this review summarizes the role of specific circRNAs in CRC and evaluates their potential value as therapeutic targets and biomarkers for CRC. We aim to provide insight in the development of therapy and clinical decision-making.     

环状RNA: 新型生物标记物与治疗靶点

环状RNA(circular RNAs,circ RNAs)是一类在真核细胞中广泛存在的非编码RNA,具有结构稳定、丰度高及细胞或组织特异性表达等特征,可能通过多种作用方式参与基因表达调控.例如,有些circ RNA富含微小RNA(mi RNAs)结合位点,可充当竞争性内源RNA(ce RNA)结合mi RNA并阻断其对靶基因表达的抑制作用.自2013年以来,circ RNA逐渐成为RNA领域的研究热点并得到广泛关注.最新研究表明,circ RNA的表达及作用与多种疾病的发生发展、生物组织发育及细胞衰老等相关.circ RNA在不同生物样本中的表达差异使其可能成为用于疾病诊断、组织发育鉴定等方面理想的生物标记物,其在疾病中作用方式的逐步阐明,使之具有成为有效治疗靶点的潜力.circ RNA数据库的构建、预测工具的开发及对其作用方式的更深入研究,必将使之具有更广阔的应用前景.     

环RNA研究概况

在1976年就已经发现RNA可以具有环形形式。但是长期以来对环形RNA(circRNAs)主要是作为一些特例加以研究。随着高通量RNA测序技术以及生物信息学的发展,近几年的研究发现circRNAs在真核生物中普遍存在,并且具有一定的保守性和细胞特异性。越来越多的证据指明circRNAs不是剪切噪音,而是具有一定生物学功能,可能与一系列调控甚至疾病的发生和发展相关。     

数字PCR定量检测血浆中环状RNA方法的建立

生物标志物一直是医学领域的研究热点.目前主要以实时荧光定量PCR技术作为分子诊断的检测手段,用于大样本的核酸检测,但该技术具有限制性,会导致假阴性.作为第三代PCR的数字PCR技术,优化并提高了检测灵敏度,无需标准曲线实现绝对定量检测,大大提高了检测的精准度,尤其是对于低表达RNA的检测,显得更为出色.本研究以hsa_circ₀061276为例,利用微滴式数字PCR EvaGreen染料法对血浆中hsa_circ₀061276的拷贝数进行绝对定量地检测,成功检测出胃炎和胃癌患者血浆中hsa_circ₀061276的具体拷贝数.因此,数字PCR作为新型检测技术在临床实际应用中有较大推广价值.     

Circular RNA expression profile in gingival tissues identifies circ_0062491 and circ_0095812 as potential treatment targets

Circular RNAs (circRNAs) emerging as a novel class of endogenous, conserved noncoding RNAs, which have been reported to be participated in immune-inflammatory response recently, yet their function in periodontal inflammation has remained elusive. This study aimed to analyze the specific circRNAs expressed in periodontal inflammation process through Illumina (San Diego, CA) sequencing technology combining with experimental validation. The inflamed and healthy gingival tissues from patients were selected to explore the expression statues of circRNAs. In brief, 1304 dysregulated circRNAs were identified in inflamed gingival tissues. Besides, Gene Ontology (GO) enrichment analysis was conducted to investigate the functions of abnormally expressed circRNAs in periodontitis as well as their host-linear genes. Furthermore, the interaction network of circRNAs-miRNAs (microRNA) was constructed to reveal the key circRNAs (circ_0095812, circ_0120299, circ_0125699, circ_0062491, and circ_0043115) in the pathobiology of periodontitis. Subsequently, we have investigated the expression pattern of circ_0062491 (downregulated) and circ_0095812 (upregulated) among 30-paired periodontitis patients and healthy individuals by quantitative real-time polymerase chain reaction. Moreover, circ_0062491 was identified as the sponge of miR-584 which play a key role in periodontitis.     

环状RNA参与鼻咽癌发生发展

环状RNA(circular RNA,circRNA)是一种具有共价闭环结构的非编码RNA(non-coding RNA,ncRNA),因其具有高稳定性、进化保守性和组织表达特异性的特点,越来越受到人们的关注。现有研究表明,circRNA参与恶性肿瘤等多种疾病的发生发展过程。鼻咽癌是一种起源于鼻咽上皮的恶性肿瘤,在中国华南和东南亚地区高发,发病与EB病毒（Epstein-Barr virus,EBV）感染密切相关。目前放疗和化疗是鼻咽癌治疗的主要手段,复发和远处转移是鼻咽癌患者死亡的主要原因。近年研究表明,circRNA作为基因表达调节因子,在鼻咽癌发生发展过程中发挥着重要的作用,影响着鼻咽癌的进展。本文主要综述了鼻咽癌中表达异常的circRNA,包括EB病毒编码的circRNA,在鼻咽癌发生发展中的研究现状,探讨了circRNA作为鼻咽癌患者治疗的潜在靶点以及诊断和预后标志物的可能性。     

Circular RNA hsa_circ_0000263 participates in cervical cancer development by regulating target gene of miR-150-5p

Circular RNA (circRNA) is a new class of noncoding RNA, and plays an important role in many pathological processes. Cervical cancer is the most common gynecologic malignant tumor. Recently, studies have shown that there is a variety of circRNA involved in the pathogenesis of cervical cancer. We screened out the highly expressed hsa_circ_0000263 from GSE102686 by the quantitative real-time polymerase chain reaction assay in cervical cancer cell lines. In this study, we investigated whether hsa_circ_0000263 might affect cell proliferation, migration, cell cycle and apoptosis in cervical cancer in vitro and in vivo. The luciferase reporter assay and RNA immunoprecipitation assay confirmed the direct interaction between miR-150-5p and hsa_circ_0000263. By using western blot and immunohistochemistry, we confirmed that hsa_circ_0000263 can regulate the expression of murine double minute 4 (MDM4) by affecting miR-150-5p, and finally affect the expression of p53 gene. We found that hsa_circ_0000263 was significantly upregulated in cervical cancer cells. In addition, the knockdown of hsa_circ_0000263, would inhibit cell proliferation and migration ability. In conclusion, our current research reveals the important role of hsa_circ_0000263/miR-150-5p/MDM4/p53 regulatory network in cervical cancer and provides a new insight into the pathogenesis of cervical cancer.     

Diagnostic and prognostic value of circular RNAs in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumour, which has posed a heavy health and financial burden worldwide. Due to limited symptoms at the early stage and the limitation in current biomarkers, HCC patients are usually diagnosed at the advanced stage with a pessimistic overall survival rate. Circular RNAs (circRNAs) are a subclass of single-stranded RNAs characterized by a covalently closed loop structure without 3’- or 5’-end. With advances in high-throughput sequencing technology and bioinformatics, accumulating studies have demonstrated the promotor or suppressor roles of circRNAs in the carcinogenesis, progression, and metastasis of HCC. Moreover, circRNAs are characteristic of higher abundance, stability and conservation compared with linear RNAs. Therefore, circRNAs have emerged as one of the most promising diagnostic and prognostic biomarkers for HCC with reliable accuracy, sensitivity and specificity. In this review, we briefly introduce the characteristics of circRNAs and summarize the roles of circRNAs in the biological procedures of HCC. Furthermore, we provide an overview on the potential diagnostic and prognostic value of circRNAs as biomarkers for patients with HCC. Finally, we discuss future perspectives of circRNAs in cancer research.     

Circular RNAs in and out of Cells: Therapeutic Usages of Circular RNAs

RNAs are versatile molecules that are primarily involved in gene regulation and can thus be widely used to advance the fields of therapeutics and diagnostics. In particular, circular RNAs which are highly stable, have emerged as strong candidates for use on next-generation therapeutic platforms. Endogenous circular RNAs control gene regulatory networks by interacting with other biomolecules or through translation into polypeptides. Circular RNAs exhibit cell-type specific expression patterns, which can be altered in tissues and body fluids depending on pathophysiological conditions. Circular RNAs that are aberrantly expressed in diseases can function as biomarkers or therapeutic targets. Moreover, exogenous circular RNAs synthesized in vitro can be introduced into cells as therapeutic molecules to modulate gene expression networks in vivo. Depending on the purpose, synthetic circular RNA sequences can either be identical to endogenous circular RNA sequences or artificially designed. In this review, we introduce the life cycle and known functions of intracellular circular RNAs. The current stage of endogenous circular RNAs as biomarkers and therapeutic targets is also described. Finally, approaches and considerations that are important for applying the available knowledge on endogenous circular RNAs to design exogenous circular RNAs for therapeutic purposes are presented.     

环状RNA在胃癌中的研究现状与策略

环状RNA (circRNA)是一种共价闭合的非编码RNA,可以调节真核生物中的基因表达.最近应用高通量RNA测序和生物信息学方法揭示人类细胞中存在大量circRNA.许多circRNA具有一定的组织和时序特异性,且与生理发育和各种肿瘤等疾病密切相关. circRNA被证明在细胞质中富集和稳定,表明其具有作为肿瘤生物标志物的潜力.胃癌(gastric carcinoma,GC)是一种常见的恶性肿瘤,在全球癌症相关死亡原因中排第3位.尽管该疾病在诊断和治疗方面取得了许多进展,但GC患者的预后仍然很差,大多数国家的5年总生存率低于30%.因此,寻找能调节GC发生发展和评估预后的新分子机制和治疗靶标至关重要.近年来circRNA在胃癌中的研究不断增多,其在胃癌的发生发展、诊断、治疗及预后过程中扮演重要角色.本文就circRNA产生机制及一般特征、生物学功能、在胃癌中的研究进展及研究中存在的问题作一综述.     

circFBXL5 promotes breast cancer progression by sponging miR‐660

Increasing studies have revealed that circular RNAs (circRNAs) play important roles in cancer progression. However, the potential involvement of circRNAs in breast cancer metastasis to lung is not clear so far. In this study, we conducted circular RNA microarrays of primary breast cancer tissues and lung metastatic tissues. The results revealed that circFBXL5 (hsa_circ_0125597) up‐regulated the most in lung metastatic tissues. Survival analysis revealed that high levels of circFBXL5 correlated with worse outcome of breast cancer. Further experiments showed that knockdown of circFBXL5 inhibited breast cancer cell proliferation and migration to lung. Mechanism study showed that circFBXL5 acted as a sponge for miR‐660 and compete binding to miR‐660 with SRSF6, leading to increased expression of SRSF6. Collectively, our study highlighted the regulatory function of the circFBXL5/miR‐660/SRSF6 pathway in breast cancer progression, which could be potential therapeutic targets for breast cancer.     

Circular RNA in renal diseases

Circular RNA (circRNA) is a newly described type of non‐coding RNA. Active research is greatly enriching the current understanding of the expression and role of circRNA, and a large amount of evidence has implicated circRNA in the pathogenesis of certain renal diseases, such as renal cell carcinoma, acute kidney injury, diabetic nephropathy and lupus nephritis. Studies have found evidence that circRNAs regulate programmed cell death, invasion, and metastasis and serve as biomarkers in renal diseases. Recently, circRNAs were identified in exosomes secreted by the kidneys. Nevertheless, the function of circRNA in renal diseases remains ambiguous. Given that circRNAs are regulators of gene expression, they may be involved in the pathology of multiple renal diseases. Additionally, emerging evidence is showing that circulating circRNAs may serve as novel biomarkers for renal disease. In this review, we have summarized the identification, biogenesis, degradation, and functions of circRNA and have evaluated the roles of circRNA in renal diseases.     

环状RNA：胃癌诊治的新星

环状RNA (circular RNA,circRNA)是一类闭合环状结构的RNA分子，广泛分布于各种组织中，它比线性RNA更稳定。circRNA分为外显子circRNA、外显子-内含子circRNA和内含子circRNA等3类。circRNA的主要功能为充当微RNA海绵、与RNA结合蛋白结合、翻译成蛋白质和调节转录等。近年来，大量研究表明，circRNA的异常表达在胃癌发生发展过程中起着至关重要的作用。circPTPN22、hsa＿circ＿0001772、circCYFIP2、hsa＿circ＿0017639和circPIP5K1A等的上调以及hsa＿circ＿002059、hsa＿circ＿0000190和circMTO1等的下调与胃癌的增殖和转移密切相关；而hsa＿circ＿0001313等影响胃癌细胞的顺铂耐药性。组织、血浆及外泌体中circPTPN22、hsa＿circ＿102958、hsa＿circ＿0141633、hsa＿circ＿0065149和hsa＿circ＿0026344等是胃癌新型诊断标志物；而hsa＿circ＿0005529、circ-RanGAP1、cir...     

Widespread and Functional RNA Circularization in Localized Prostate Cancer

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