Aberrant miRNA Expression Profiles Research Articles

Novel microRNAs modulating ecto-5'-nucleotidase expression.

The expression of immune checkpoint molecules (ICMs) by cancer cells is known to counteract tumor-reactive immune responses, thereby promoting tumor immune escape. For example, upregulated expression of ecto-5'-nucleotidase (NT5E), also designated as CD73, increases extracellular levels of immunosuppressive adenosine, which inhibits tumor attack by activated T cells. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Thus, the binding of miRNAs to the 3'-untranslated region of target mRNAs either blocks translation or induces degradation of the targeted mRNA. Cancer cells often exhibit aberrant miRNA expression profiles; hence, tumor-derived miRNAs have been used as biomarkers for early tumor detection. In this study, we screened a human miRNA library and identified miRNAs affecting the expression of ICMs NT5E, ENTPD1, and CD274 in the human tumor cell lines SK-Mel-28 (melanoma) and MDA-MB-231 (breast cancer). Thereby, a set of potential tumor-suppressor miRNAs that decreased ICM expression in these cell lines was defined. Notably, this study also introduces a group of potential oncogenic miRNAs that cause increased ICM expression and presents the possible underlying mechanisms. The results of high-throughput screening of miRNAs affecting NT5E expression were validated in vitro in 12 cell lines of various tumor entities. As result, miR-1285-5p, miR-155-5p, and miR-3134 were found to be the most potent inhibitors of NT5E expression, while miR-134-3p, miR-6859-3p, miR-6514-3p, and miR-224-3p were identified as miRNAs that strongly enhanced NT5E expression levels. The miRNAs identified might have clinical relevance as potential therapeutic agents and biomarkers or therapeutic targets, respectively.

MicroRNAs as clinical tools for diagnosis, prognosis, and therapy in prostate cancer

Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men worldwide. Despite the presence of accumulated clinical strategies for PCa management, limited prognostic/sensitive biomarkers are available to follow up on disease occurrence and progression. MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression through post-transcriptional regulation of their complementary target messenger RNA (mRNA). MiRNAs modulate fundamental biological processes and play crucial roles in the pathology of various diseases, including PCa. Multiple evidence proved an aberrant miRNA expression profile in PCa, which is actively involved in the carcinogenic process. The robust and pleiotropic impact of miRNAs on PCa suggests them as potential candidates to help more understand the molecular landscape of the disease, which is likely to provide tools for early diagnosis and prognosis as well as additional therapeutic strategies to manage prostate tumors. Here, we emphasize the most consistently reported dysregulated miRNAs and highlight the contribution of their altered downstream targets with PCa hallmarks. Also, we report the potential effectiveness of using miRNAs as diagnostic/prognostic biomarkers in PCa and the high-throughput profiling technologies that are being used in their detection. Another key aspect to be discussed in this review is the promising implication of miRNAs molecules as therapeutic tools and targets for fighting PCa.

The Potential of MicroRNAs as Clinical Biomarkers to Aid Ovarian Cancer Diagnosis and Treatment.

Ovarian cancer is a commonly diagnosed malignancy in women. When diagnosed at an early stage, survival outcomes are favourable for the vast majority, with up to 90% of ovarian cancer patients being free of disease at 5 years follow-up. Unfortunately, ovarian cancer is typically diagnosed at an advanced stage due to the majority of patients remaining asymptomatic until the cancer has metastasised, resulting in poor outcomes for the majority. While the molecular era has facilitated the subclassification of the disease into distinct clinical subtypes, ovarian cancer remains managed and treated as a single disease entity. MicroRNAs (miRNAs) are small (19-25 nucleotides), endogenous molecules which are integral to regulating gene expression. Aberrant miRNA expression profiles have been described in several cancers, and have been implicated to be useful biomarkers which may aid cancer diagnostics and treatment. Several preliminary studies have identified candidate tumour suppressor and oncogenic miRNAs which may be involved in the development and progression of ovarian cancer, highlighting their candidacy as oncological biomarkers; understanding the mechanisms by which these miRNAs regulate the key processes involved in oncogenesis can improve our overall understanding of cancer development and identify novel biomarkers and therapeutic targets. This review highlights the potential role of miRNAs which may be utilised to aid diagnosis, estimate prognosis and enhance therapeutic strategies in the management of primary ovarian cancer.

Epigenetic regulation of inflammation by microRNAs in post-infectious bronchiolitis obliterans.

ObjectivesPost‐infectious bronchiolitis obliterans (PiBO) is a rare, chronic disease initiated by severe infection and followed by perpetuating inflammation and obliteration of the small airways. MicroRNAs (miRNAs) have been proposed to play a central role as epigenetic regulators, which control resolution and prevent the uncontrolled progress of inflammation. The aim of this study was to define biomarkers on the level of post‐transcriptional gene regulation in order to characterise PiBO.MethodsA total of 39 patients with well‐defined PiBO and 31 controls from two centres, Barcelona, Spain, and Frankfurt, Germany, were analysed by next‐generation sequencing (NGS). The evaluation of the biological targets of the miRNAs was performed by pathway enrichment analysis and protein–protein interaction network analysis respectively.ResultsPatients with PiBO had significantly lower lung function values and increased airway inflammation in induced sputum as indicated by total cell counts, neutrophils, IL‐1β, IL‐6, IL‐8 and TGF‐β compared to controls.Next‐generation sequencing analysis revealed a total of 22 dysregulated miRNAs, which passed significance threshold for Padj ≤ 0.001 with 17 being upregulated and 5 being downregulated. Of these dysregulated miRNAs, miR‐335‐5p, miR‐186‐5p, miR‐30b‐5p and miR‐30c‐5p were further validated using qRT‐PCR. Interestingly, these miRNAs are functionally implicated in cytokine–cytokine receptor interaction, TGF‐β signalling and FoxO signalling pathway and significantly correlated with lung function values (FEV1).ConclusionOur results demonstrate an aberrant miRNA expression profile in PiBO, which impacts pathways responsible for the regulation of inflammation and fibrosis. The defined miRNAs are useful biomarkers and should be assessed as potential target in the field of miRNA therapeutics.

The Role of MicroRNA as Clinical Biomarkers for Breast Cancer Surgery and Treatment.

Breast cancer is the most common cancer diagnosed in women. In recent times, survival outcomes have improved dramatically in accordance with our enhanced understanding of the molecular processes driving breast cancer proliferation and development. Refined surgical approaches, combined with novel and targeted treatment options, have aided the personalisation of breast cancer patient care. Despite this, some patients will unfortunately succumb to the disease. In recent times, translational research efforts have been focused on identifying novel biomarkers capable of informing patient outcome; microRNAs (miRNAs) are small non-coding molecules, which regulate gene expression at a post-transcriptional level. Aberrant miRNA expression profiles have been observed in cancer proliferation and development. The measurement and correlation of miRNA expression levels with oncological outcomes such as response to current conventional therapies, and disease recurrence are being investigated. Herein, we outline the clinical utility of miRNA expression profiles in informing breast cancer prognosis, predicting response to treatment strategies as well as their potential as therapeutic targets to enhance treatment modalities in the era of precision oncology.

Potential Interactions between miRNAs and Hypoxia: A New Layer in Cancer Hypoxia

Hypoxia pathway and aberrant miRNA expression profile play crucial roles in the development of various cancers. Recent studies have emphasized that there are many collaborations in this cases because both of them are involved in cancer cell processes, including differentiation, metastasis, and cell proliferation and signaling pathways. Further studies have elucidated that miRNAs affect the hypoxia route, and more interestingly, the hypoxia pathway also affects miRNAs expression profile. The literature review summarizes the fundamental roles of hypoxia-related miRNAs in different cancers. The mutual interactions between miRNAs and hypoxia are a new layer of complexity in cancer hypoxia, which might be helpful in controlling cancer progression. It is also possible that the hypoxia pathway is initiated by miRNAs. In contrast, the hypoxia pathway regulates the expression of a large group of miRNAs. In this review for the first time, we discussed the significant interactions between hypoxia and miRNAs in order to determine new perspectives for new therapeutic aims in the field of cancer.

MicroRNAs involved in T-cell development, selection, activation, and hemostasis.

MicroRNAs (miRNAs) characterized by small, noncoding RNAs have a fundamental role in the regulation of gene expression at the post-transcriptional level. Additionally, miRNAs have recently been identified as potential regulators of various genes involved in the pathogenesis of the autoimmune and inflammatory disease. So far, the interaction between miRNAs and T lymphocytes in the immune response as a new and significant topic has not been emphasized substantially. The role of miRNAs in different biological processes including apoptosis, immune checkpoints and the activation of immune cells is still unclear. Aberrant miRNA expression profile affects various aspects of T-cell function. Accordingly, in this literature review, we summarized the role of significant miRNAs in T-cell development processes. Consequently, we demonstrated precise mechanisms that candidate miRNAs interfere in Immune response mediated by different types of T cells. We believe that a good understanding of the interaction between miRNAs and immune response contributes to the new therapeutic strategies in relation to disease with an immunological origin.

Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression.

Several phytochemicals have been identified for their role in modifying miRNA regulating tumor progression. miRNAs modulate the expression of several oncogenes and tumor suppressor genes including the genes that regulate tumor angiogenesis. Hypoxia inducible factor-1 alpha (HIF-1α) signaling is a central axis that activates oncogenic signaling and acts as a metabolic switch in endothelial cell (EC) driven tumor angiogenesis. Tumor angiogenesis driven by metabolic reprogramming of EC is crucial for tumor progression and metastasis in many different cancers, including breast cancers, and has been linked to aberrant miRNA expression profiles. In the current article, we identify different miRNAs that regulate tumor angiogenesis in the context of oncogenic signaling and metabolic reprogramming in ECs and review how selected phytochemicals could modulate miRNA levels to induce an anti-angiogenic action in breast cancer. Studies involving genistein, epigallocatechin gallate (EGCG) and resveratrol demonstrate the regulation of miRNA-21, miRNA-221/222 and miRNA-27, which are prognostic markers in triple negative breast cancers (TNBCs). Modulating the metabolic pathway is a novel strategy for controlling tumor angiogenesis and tumor growth. Cardamonin, curcumin and resveratrol exhibit their anti-angiogenic property by targeting the miRNAs that regulate EC metabolism. Here we suggest that using phytochemicals to target miRNAs, which in turn suppresses tumor angiogenesis, should have the potential to inhibit tumor growth, progression, invasion and metastasis and may be developed into an effective therapeutic strategy for the treatment of many different cancers where tumor angiogenesis plays a significant role in tumor growth and progression.

Nanocurcumin restores aberrant miRNA expression profile in multiple sclerosis, randomized, double-blind, placebo-controlled trial.

In the current study, we aimed to identify nanocurcumin effects on microRNAs (miRNAs) in the peripheral blood of patients with relapsing-remitting multiple sclerosis (RRMS). We intended to investigate the expression pattern of these miRNAs in experimental settings in vivo. The expression levels of the selected 27 miRNAs known to be involved in the regulation of immune responses were analyzed in 50 RRMS patients and 35 healthy controls. The miRNA expression profiles were investigated by quantitative PCR (qPCR) at baseline and after 6 months of nanocurcumin therapy. Our data revealed that the expression of a number of microRNAs including miR-16, miR-17-92, miR-27, miR-29b, miR-126, miR-128, miR-132, miR-155, miR-326, miR-550, miR-15a, miR-19b, miR-106b, miR-320a, miR-363, miR-31, miR-150, and miR-340 is regulated by nanocurcumin. The results of the current work indicate that nanocurcumin is able to restore the expression pattern of dysregulated miRNAs in MS patients. We discovered that some miRNAs are deregulated in untreated patients compared with healthy controls and nanocurcumin-treated patients. This is a new finding that might represent the potential contribution of these miRNAs to MS pathogenesis. Taken together, these data provide novel insights into miRNA-dependent regulation of the function of B and T cells in MS disease and enrich our understanding of the effects mediated by a therapeutic approach that targets B and T cells.

Dysregulation of miRNAs in bladder cancer: altered expression with aberrant biogenesis procedure.

Aberrant expression profiles of miRNAs are widely observed in the clinical tissue specimens and urine samples as well as the blood samples of bladder cancer patients. These profiles are closely related to the pathological features of bladder cancer, such as the tumour stage/grade, metastasis, recurrence and chemo-sensitivity. MiRNA biogenesis forms the basis of miRNA expression and function, and its dysregulation has been shown to be essential for variations in miRNA expression profiles as well as tumourigenesis and cancer progression. In this review, we summarize the up-to-date and widely reported miRNAs in bladder cancer that display significantly altered expression. We then compare the miRNA expression profiles among three different sample types (tissue, urine and blood) from patients with bladder cancer. Moreover, for the first time, we outline the dysregulated miRNA biogenesis network in bladder cancer from different levels and analyse its possible relationship with aberrant miRNA expression and the pathological characteristics of the disease.

MicroRNA Biomarkers in Neurodegenerative Diseases and Emerging Nano-Sensors Technology.

MicroRNAs (miRNAs) are essential small RNA molecules (20–24 nt) that negatively regulate the expression of target genes at the post-transcriptional level. Due to their roles in a variety of biological processes, the aberrant expression profiles of miRNAs have been identified as biomarkers for many diseases, such as cancer, diabetes, cardiovascular disease and neurodegenerative diseases. In order to precisely, rapidly and economically monitor the expression of miRNAs, many cutting-edge nanotechnologies have been developed. One of the nanotechnologies, based on DNA encapsulated silver nanoclusters (DNA/AgNCs), has increasingly been adopted to create nanoscale bio-sensing systems due to its attractive optical properties, such as brightness, tuneable emission wavelengths and photostability. Using the DNA/AgNCs sensor methods, the presence of miRNAs can be detected simply by monitoring the fluorescence alteration of DNA/AgNCs sensors. We introduce these DNA/ AgNCs sensor methods and discuss their possible applications for detecting miRNA biomarkers in neurodegenerative diseases.

Expression of miR‑26a exhibits a negative correlation with HMGA1 and regulates cancer progression by targeting HMGA1 in lung adenocarcinoma cells.

Lung cancer is the most common cause of cancer-associated mortality worldwide, and the number of cases is increasing annually. Several studies have shown that microRNAs (miRNAs) control proliferation, differentiation, and apoptosis in various cell types, and increasing evidence indicates the presence of aberrant miRNA expression profiles and unique miRNA signaling pathways in several types of cancer. The present study aimed to identify miRNAs, which correlated specifically with the progression of lung cancer through the analysis of 57,100 transcripts and 1,341 small RNA expression profiles in 26 lung adenocarcinoma cell lines using next-generation sequencing. The most marked negative correlation was found between the expression of hsa-miR-26a-1 and messenger RNA (mRNA), and a list of mRNAs, which exhibited negative correlation with hsa-miR-26a-1 were investigated. The most marked negative correlation was observed between the expression levels of hsa-miR-26a-1 and high mobility group A1 (HMGA1). Using a lung adenocarcinoma cell line, the present study analyzed the effect of the overexpression of miR-26a on the expression of HMGA1 and found that miR-26a repressed the expression of HMGA1 by reducing the mRNA levels of HMGA1. Furthermore, it was demonstrated that the overexpression of miR-26a in a lung adenocarcinoma cell line repressed cell migration, invasion and growth by targeting HMGA1. Taken together, the present study showed a significant negative correlation between the expression of miR-26a and HMGA1 in 26 lung adenocarcinoma cell lines, and provided evidence that the suppression of miR-26a supports the progression of cancer by stimulating the expression of HMGA1.

Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer.

Human gastric cancer (GC) is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients’ survival rate. MicroRNAs (miRNAs) play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets.

Benzene-Induced Aberrant miRNA Expression Profile in Hematopoietic Progenitor Cells in C57BL/6 Mice.

Benzene is a common environmental pollutant that causes hematological alterations. MicroRNAs (miRNAs) may play a role in benzene-induced hematotoxicity. In this study, C57BL/6 mice showed significant hematotoxicity after exposure to 150 mg/kg benzene for 4 weeks. Benzene exposure decreased not only the number of cells in peripheral blood but also hematopoietic progenitor cells in the bone marrow. Meanwhile, RNA from Lin− cells sorted from the bone marrow was applied to aberrant miRNA expression profile using Illumina sequencing. We found that 5 miRNAs were overexpressed and 45 miRNAs were downregulated in the benzene exposure group. Sequencing results were confirmed through qRT-PCR. Furthermore, we also identified five miRNAs which significantly altered in Lin−c-Kit+ cells obtained from benzene-exposed mice, including mmu-miR-34a-5p; mmu-miR-342-3p; mmu-miR-100-5p; mmu-miR-181a-5p; and mmu-miR-196b-5p. In summary, we successfully established a classical animal model to induce significant hematotoxicity by benzene injection. Benzene exposure may cause severe hematotoxicity not only to blood cells in peripheral circulation but also to hematopoietic cells in bone marrow. Benzene exposure also alters miRNA expression in hematopoietic progenitor cells. This study suggests that benzene induces alteration in hematopoiesis and hematopoiesis-associated miRNAs.

MicroRNA Expression Profile Reveals miR-17-92 and miR-143-145 Cluster in Synchronous Colorectal Cancer.

The expression of abnormal microRNA (miRNA, miR) is a ubiquitous feature of colorectal cancer (CRC). The pathological features and clinical behaviors of synchronous CRC have been comprehensively described; however, the expression profile of miRNA and small nucleolar RNA (snoRNA) in synchronous CRC has not been elucidated. In the present study, the expression profile of miRNA and snoRNA in 5 synchronous CRCs, along with the matched normal colorectal tissue was evaluated by microarray. Function and pathway analyses of putative targets, predicted from miRNA-mRNA interaction, were performed. Moreover, we analyzed clinicopathological and molecular characteristics of 22 patients with synchronous CRC and 579 solitary CRCs in a retrospective cohort study. We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC. Differential miRNA rather than snoRNA expression was robust enough to distinguish synchronous cancer from normal mucosa. Function analysis of putative targets suggested that miRNA clusters may modulate multiple effectors of oncogenic pathways involved in the pathogenesis of synchronous CRC. A comparison of normal mucosa between synchronous and solitary CRC suggested a differential genetic background of synchronous CRC from solitary CRC during carcinogenesis. Compared with solitary cancer patients, synchronous cases exhibited multiple extra-colonic cancers (P = 0.012), coexistence of adenoma (P = 0.012), microsatellite instability (P = 0.024), and less glucose transporter 1 (P = 0.037). Aberrant miRNA expression profiles could potentially be used as a diagnostic tool for synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, implicating that the miRNAs and snoRNAs may present therapeutic targets for synchronous CRC.

MicroRNA signatures differentiate Crohn's disease from ulcerative colitis.

BackgroundExcessive and inappropriate immune responses are the hallmark of several autoimmune disorders, including the inflammatory bowel diseases (IBD): Crohn’s disease (CD) and ulcerative colitis (UC). A complex etiology involving both environmental and genetic factors influences IBD pathogenesis. The role of microRNAs (miRNAs), noncoding RNAs involved in regulating numerous biological processes, to IBD pathology, in terms of initiation and progression, remains ill-defined. In the present study, we evaluated the relationship between colon, peripheral blood, and saliva whole miRNome expression in IBD patients and non-inflammatory bowel disease (non-IBD) controls to identify miRNAs that could discriminate CD from UC. Quantitative real-time PCR (qRT-PCR) was used to validate and assess miRNA expression.ResultsMicroarray analysis demonstrated that upwards of twenty six miRNAs were changed in CD and UC colon biopsies relative to the non-IBD controls. CD was associated with the differential expression of 10 miRNAs while UC was associated with 6 miRNAs in matched colon tissues. CD was associated with altered expression of 6 miRNAs while UC was associated with 9 miRNAs in whole blood. Expression of miR-101 in CD patients and miR-21, miR-31, miR-142-3p, and miR-142-5p in UC patients were altered in saliva.ConclusionsOur results suggest that there is specific miRNA expression patterns associated with UC versus CD in three separate tissue/body fluids (colon, blood, and saliva). Further, the aberrant miRNA expression profiles indicate that miRNAs may be contributory to IBD pathogenesis, or at least reflect the underlying inflammation. Scrutinizing miRNA expression in saliva and blood samples may be beneficial in monitoring or diagnosing disease in IBD patients. A panel of miRNAs (miR-19a, miR-21, miR-31, miR-101, miR-146a, and miR-375) may be used as markers to identify and discriminate between CD and UC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-015-0069-0) contains supplementary material, which is available to authorized users.

MicroRNAs as potential biomarkers in cancer: opportunities and challenges.

MicroRNAs (miRNAs) are a group of small noncoding RNAs (ncRNAs) that posttranscriptionally regulate gene expression by targeting their corresponding messenger RNAs (mRNAs). Dysregulated miRNAs have been considered as a new type of ‘‘oncomiRs” or ‘‘tumor suppressors,” playing essential roles in cancer initiation and progression. Using genome-wide detection methods, ubiquitously aberrant expression profiles of miRNAs have been identified in a broad array of human cancers, showing great potential as novel diagnostic and prognostic biomarkers of cancer with high specificity and sensitivity. The detectable miRNAs in tissue, blood, and other body fluids with high stability provide an abundant source for miRNA-based biomarkers in human cancers. Despite the fact that an increasing number of potential miRNA biomarkers have been reported, the transition of miRNAs-based biomarkers from bench to bedside still necessitates addressing several challenges. In this review, we will summarize our current understanding of miRNAs as potential biomarkers in human cancers.

Dysregulated Serum MicroRNA Expression Profile and Potential Biomarkers in Hepatitis C Virus-infected Patients.

Objectives: Circulating microRNAs (miRNAs) play critical roles in pathogen-host interactions. Aberrant miRNA expression profiles might have specific characteristics for virus strains, and could serve as noninvasive biomarkers for screening and diagnosing infectious diseases. In this study, we aimed to find new potential miRNA biomarkers of hepatitis C virus (HCV) infection.Methods: Expression levels of broad-spectrum miRNAs in serum samples from 10 patients with HCV viremia and 10 healthy volunteers were analyzed using miRNA PCR arrays. Subsequently, the differential expression of four selected miRNAs (miR-122, miR-134, miR-424-3p, and miR-629-5p) was verified by qRT-PCR in the serum of 39 patients compared with that in 29 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate their potential for the diagnosis of HCV infection.Results: miRNA PCR array assays revealed differential expression of 106 miRNAs in sera of HCV patients compared with that in healthy controls. Serum hsa-miR-122, miR-134, miR-424-3p, and miR-629-5p were well identified. The ROC curves showed that miR-122, miR-134, miR-424-3p, and miR-629-5p could distinguish HCV patients with preferable sensitivity and specificity. In addition, Correlation analysis indicated serum miR-122 expression was positive correlation with ALT/AST levels. Functional analysis of target proteins of these miRNAs indicated the involvement of viral replication, inflammation, and cell proliferation.Conclusion: HCV patients have a broad 'fingerprint' profile with dysregulated serum miRNAs compared with that in healthy controls. Among these, serum hsa-miR-122, miR-134, miR-424-3p, and miR-629-5p are identified as promising indication factors of the serum miRNA profile of HCV infection. Particularly, miR-122 could be one of serum biomarkers for early pathological process of HCV. However, more miRNA biomarkers and biological functions of these miRNAs require further investigation.

MiR-30e induces apoptosis and sensitizes K562 cells to imatinib treatment via regulation of the BCR–ABL protein

Chronic myeloid leukemia (CML) is a disorder of hematopoietic stem cell carrying the Philadelphia (Ph) chromosome and an oncogenic BCR–ABL fusion gene. Tyrosine kinase inhibitors (TKIs) of the BCR–ABL kinase are the treatment of choice for CML patients. Imatinib was the first TKI used in clinical practice with excellent results. MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression and play an important role in cancer development and progression. Aberrant miRNA expression profiles have been shown to be characteristic of many cancers. Here, we demonstrate that miR-30e is expressed at low levels in CML cell lines and patient samples. Bioinformatics analysis reveals a putative target site for miR-30e in the 3′-untranslated region (UTR) of the ABL gene. In agreement, luciferase assay verified that miR-30e directly targets ABL. Enforced expression of miR-30e in K562 cells suppressed proliferation and induced apoptosis of these cells and sensitized them to imatinib treatment. These findings strongly suggest that miR-30e acts as a tumor suppressor by downregulating BCR–ABL expression. Up-regulation of miR-30e in CML cells may therefore have a therapeutic efficacy against this disease.

MicroRNA Therapeutics: The Emerging Anticancer Strategies

The genetic alterations and aberrant miRNA expression profiles have been identified as important events behind the emergence of cancer. This knowledge triggers the use of miRNA therapeutics as an anticancer strategy. Basically, MicroRNAs (miRNAs) are approximately 22-nucleotide long, endogenous non-protein-coding RNA molecules which function as important regulatory molecules that regulate gene and protein expression through the RNA interference (RNAi) machinery. Transcription of these molecules by RNA polymerases II and III, resulting in the generation of precursor microRNAs that undergo a series of cleavage events, consequently, generate the mature microRNA. The biogenesis pathway is mediated by the two important cleavage events such as nuclear and cytoplasmic. The regulatory functions of microRNAs are accomplished through the RNA-induced silencing complex (RISC), leading to translational repression and hence, regulate the gene expression. The current progress in the development of strategies for miRNA-based anticancer therapies is due to its involvement in cellular, developmental and biological processes including regulation in cancer cell and modulation by various cancer chemoprophylaxis agents. Although miRNA therapeutics have been found to suppress gene expression effectively as compared to anti-sense oligonucleotide strategies, but it is bound with some limitations viz. identification of tissue specific miRNA, biological instability, off-target effects and delivery in the cell system. Up to certain extent, these hurdles have been resolved by chemical modifications using cholesterol conjugation, morpholinos, cationic lipids and cationic nanoparticles. Still more research is needed to understand the mechanism of action for better miRNA therapeutics. The paper discusses the potential miRNA therapeutics and diagnostic applications for cancer prevention, based on recent patents and their analysis.