Small molecule with big role: MicroRNAs in cancer metastatic microenvironments

Cancer metastasis is closely related to tumor cell microenvironments. Cancer cells and stromal cells interact with one another through extracellular matrix (ECM) and jointly participate in establishing the microenvironments. However, many questions remain to be addressed, in particular, a crucial question is which messengers mediate the mutual interaction and regulation between cancer cells and stromal cells. MicroRNAs (miRNAs), as oncogenic and oncosuppressor genes, regulate the expression and function of their related target genes to affect the biological behaviors of cancer cells and stromal cells, which may play an important role in cancer metastasis. Many miRNAs associated with cancer metastasis have been identified. The molecules of miRNAs are small and relatively easy to be secreted into extracellular microenvironments and devoured by nearby cells. As the regulatory messengers between cells, the secreted miRNAs function to regulate cancer cell proliferation, migration, intercellular communication and stromal modification, thereby helping cancer cells to establish their microenvironments for metastasis. In conclusion, miRNAs are small molecules, but they play a powerful role in regulating cancer metastatic ability by construction and modification of microenvironments.     

MicroRNAs and the hallmarks of cancer

It has become clear that particular microRNAs (miRNAs) function either as tumour suppressors or oncogenes, whose loss or overexpression, respectively, has diagnostic and prognostic significance. In several cases, miRNAs have been shown to affect target genes that are involved in the control of cell proliferation and apoptosis. However, malignant tumours display additional traits beyond the acquisition of enhanced growth potential and decreased cell death. Malignant disease is associated with altered tumour-host interactions leading to sustained angiogenesis and the ability to invade and metastasize. It is possible that miRNAs may act as master regulators of these aspects of tumour biology. Bioinformatic analysis of putative miRNA binding sites has indicated several novel potential gene targets of cancer-associated miRNAs that function in aspects of cell adhesion, neovascularization and tissue invasion. Among others, we speculate that miRNAs may find new roles in the regulation of E-cadherin, integrin alphavbeta3, hypoxia-inducible factor-1alpha, syndecan-1, lysyl oxidase, adamalysin metalloproteinase-17, tissue inhibitors of metalloproteinase-3, c-Met and CXCR-4 that underpin the tissue architectural changes associated with malignancy.     

Novel perspective: focusing on the X chromosome in reproductive cancers

In an XX female, one of the two X chromosomes has been inactivated during early embryonic life to achieve a compensation of X-linked gene products between males and females, leaving only one allele of X-linked genes functional. There are some X-linked genes escaping the X-inactivation, i.e., being expressed from both alleles. Escape from X-inactivation varies at different levels; some genes have both alleles active in some women but only one allele active in others, whereas some other genes have both alleles active in neoplastic tissue but only one allele active normally. The X-inactivation may be considered functionally equivalent to a loss of heterozygosity (LOH) for some genes, whereas escape from X-inactivation may be equivalent to functional gene amplification for others. The physiological LOH may make X-linked tumor suppressor genes lose their function more easily, compared with autosomal tumor suppressor genes, thus predisposing women to cancer formation more easily. Moreover, the human X chromosome contains many genes related to cancer or to sex and reproduction. All these properties of the X chromosome suggest that it may play more important roles than any autosomal chromosome in the development and progression of reproductive and urologic cancers.     

microRNAs与胃癌治疗

microRNAs（miRNAs）是真核生物中一类小分子非编码单链RNA,在转录后水平上调控靶mRNA的表达。目前,miRNA功能学研究发现miRNA与胃癌的侵袭转移、化疗耐药、放疗增敏、血管形成、基因甲基化、诊断和预后有直接关系,提示miRNA有可能成为肿瘤治疗的新思路。本文将阐述miRNA和胃癌放化疗的关系及其作为诊断、预后因子和基因治疗靶点基础研究方面的新进展。     

MicroRNAs:regulators of cancer metastasis and epithelial-mesenchymal transition (EMT)

Tumor metastasis is the main cause of death in patients with solid tumors. The epithelial-mesenchymal transition(EMT) process, in which epithelial cells are converted into mesenchymal cells, is frequently activated during cancer invasion and metastasis. MicroRNAs(miRNAs) are small, non-coding RNAs that provide widespread expressional control by repressing mRNA translation and inducing mRNA degradation. The fundamental roles of miRNAs in tumor growth and metastasis have been increasingly well recognized. A growing number of miRNAs are reported to regulate tumor invasion/metastasis through EMT-related and/or non-EMT–related mechanisms. In this review, we discuss the functional role and molecular mechanism of miRNAs in regulating cancer metastasis and EMT.     

MicroRNAs in tumor stem cells

MicroRNAs (miRNAs) are a class of non-coding RNAs that are believed to have a significant role in tumori-genesis and cancer metastasis. Cancer stem cel s play a major role in tumor recurrence, metastas...     

非小细胞肺癌不同组织标本中P16基因的PCR-SSCP分析

目的 :研究非小细胞肺癌 (NSCLC)不同来源与病理分期类型的组织标本中P16基因表达的相互关系。方法 :应用PCR -SSCP方法 ,检测 2 8例手术标本、2 1例支气管镜活检及 2 7例恶性胸水NSCLC患者中P16基因的表达。结果 :2 8例Ⅰ期手术标本中 8例P16基因发生改变 (2 8 6 % ) ,其中 5例纯合性缺失 ,3例点突变 ;2 1例支气管镜活检中 ,8例P16基因发生改变 (38 1% ) ,其中 3例纯合性缺失 ,5例点突变 ;2 7例恶性胸水标本中 ,17例P16基因发生改变 (6 3 0 % ) ,其中 16例纯合性缺失 ,1例点突变。恶性胸水患者的P16基因改变率与Ⅰ期手术标本、支气管镜活检相比较 ,有显著性差异 (分别为P <0 0 1、P<0 0 0 5 )。在 76例NSCLC中 ,Ⅰ期患者的P16基因改变率为 30 0 % (9/ 30 ) ,Ⅱ期患者为 5 0 % (2 / 4 ) ,Ⅲ期患者为 5 1 6 % (16 /31) ,Ⅳ期患者为 5 4 5 % (6 / 11)。Ⅰ期患者的P16基因改变率与Ⅱ、Ⅲ、Ⅳ期患者相比较 ,均有显著性差异 (P <0 0 5 )。腺癌患者的P16基因改变率为 4 5 0 % (18/ 4 0 ) ,鳞癌患者为 4 2 3% (11/ 2 6 ) ,而腺鳞癌混合型为 4 0 0 % (4/ 10 ) ,经统计学分析 ,三者无显著性差异。而鳞癌患者的P16基因突变率为 2 3 1% (6 / 2 6 ) ,腺癌患者为 7 5 % (3/ 4 0 ) ,二者有显著性差异 (P <0 0     

MicroRNAs in the diagnosis, prognosis and treatment of cancer

MicroRNAs (miRNAs) are small non-coding RNAs that regulate critical cell processes such as cell proliferation, apoptosis and differentiation by modulating gene expression. MiRNAs deregulation has been observed extensively in cancer. Elegant studies have demonstrated that miRNAs are involved in the initiation and progression of several malignancies. In this review we will address the role of miRNAs in the diagnosis and prognosis of cancer. The development of new drugs mimicking or blocking miRNAs will be discussed.     

MicroRNAs in colorectal cancer: Function, dysregulation and potential as novel biomarkers

Background

MicroRNAs (miRNAs) are short non-coding segments of RNA which are involved in normal cellular development and proliferation. Recent studies have identified altered miRNA expression in both tumour tissues and circulation in the presence of colorectal cancer. These altered expression patterns may serve as novel biomarkers for colorectal cancer. This review explores recent developments in this rapidly evolving field.

Methods

A thorough literature search was performed to identify studies describing miRNA expression in colorectal cancer. Specific areas of interest included miRNA expression patterns in relation to development, diagnosis, progression and recurrence of disease, and potential future therapeutic applications.

Results

MiRNAs are associated with the development and progression of colorectal cancer. These may be either overexpressed or underexpressed (depending on the specific miRNA). Although there are fewer published studies regarding circulating miRNAs, these appear to be reflective of alterations in tissue expression and may have a potential role as minimally invasive biomarkers.

Conclusion

MiRNAs have immense potential for refinement of the current processes for diagnosis, staging and prognostic prediction. They may also provide potential future therapeutic targets in the management of colorectal cancer.     

microRNAs在肿瘤干细胞中的研究进展

microRNAs（miRNAs）是一类非编码的小RNA,在肿瘤发生发展及侵袭转移中发挥着至关重要的作用。肿瘤干细胞是导致恶性肿瘤复发、转移和耐药的主要根源。研究发现miRNAs可以促进或抑制肿瘤干细胞“干性”的维持,调控肿瘤干细胞的分化及自我更新,从而参与肿瘤的发生发展过程。本文详细介绍了肿瘤干细胞中miRNAs的表达情况及调控机制,阐述其在肿瘤诊断及治疗中的潜在作用。     

Expression of the Grb2-related RET adapter protein Grap-2 in human medullary thyroid carcinoma

Inappropriate signaling of the RET receptor tyrosine kinase causes different forms of human thyroid malignancy. We have previously identified the adaptor Grap-2 as RET binding protein. To verify involvement of Grap-2 in RET oncogenic signaling we performed sequence and expression analysis of Grap-2 in 15 human MTC samples. All tumors displayed marked Grap-2 mRNA and protein expression without a linear correlation. Beyond one conservative base pair substitution we detected no further alteration in genomic Grap-2 sequence. Consistent Grap-2 expression suggests a specific role for this adaptor in human MTC, while qualitative alterations do not appear to influence RET signaling.     

微小RNA:肿瘤耐药治疗新靶点

肿瘤的多药耐药(multidrug resistance,MDR)是临床化疗失败的主要原因之一,但其耐药性机制至今尚未完全阐明.最近研究表明,微小RNA(miRNA) 对多基因表达的调控具有高效性和特异性,对靶基因的异常调控可能构成肿瘤耐药机制,是肿瘤耐药复杂性调控的重要构成部分.因此,对微小RNA与肿瘤耐药性研究具有现实意义.本文对近年来微小RNA与各种肿瘤耐药的关系及微小RNA作为肿瘤治疗潜在靶点的研究进展作一综述.     

A STUDY OF MULTI-GENE EXPRESSION IN THE HIGHLY METASTASIZING HUMAN OVARIAN CANCER CELL LINE HO-8910PM AND ITS MOTHER CELL LINE HO-8910

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Biphasic regulation of autophagy by miR-96 in prostate cancer cells under hypoxia

Autophagy favors cell survival under hypoxia, and increasing evidence revealed that microRNAs regulate autophagy. We report here hypoxia increased the expression of miR-96 in prostate cancer cells, and miR-96 stimulated autophagy by suppressing MTOR. We found that inhibition of miR-96 abolished hypoxia-induced autophagy. Paradoxically, ectopic over-expression of miR-96 to a certain threshold, also abolished the hypoxia-induced autophagy. Further studies have shown that high levels of miR-96 inhibited autophagy through suppressing ATG7, a key autophagy-associated gene. Importantly, the miR-96 expression level threshold was determined, and the effects of miR-96 on autophagy on either side of the threshold were opposite. These data demonstrate hypoxia-induced autophagy is at least partially regulated by miR-96; miR-96 can promote or inhibit autophagy by principally inhibiting MTOR or ATG7 depending on the expression levels of miR-96. Our observation might reveal a novel regulatory mode of autophagy by microRNAs under hypoxia.