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14 pages, 768 KiB

Open AccessCommunication

Expression Profile and Clinical Significance of MicroRNAs in Papillary Thyroid Carcinoma

by You Peng, Chen Li, Ding-Cun Luo, Jin-Wang Ding, Wo Zhang and Gang Pan

Molecules 2014, 19(8), 11586-11599; https://doi.org/10.3390/molecules190811586 - 5 Aug 2014

Cited by 66 | Viewed by 7565

Abstract

This study screened microRNAs (miRNAs) that are abnormally expressed in papillary thyroid carcinoma (PTC) tissues to identify PTC and nodular goiter and the degree of PTC malignancy. A total of 51 thyroid tumor tissue specimens paired with adjacent normal thyroid tissues were obtained [...] Read more.

This study screened microRNAs (miRNAs) that are abnormally expressed in papillary thyroid carcinoma (PTC) tissues to identify PTC and nodular goiter and the degree of PTC malignancy. A total of 51 thyroid tumor tissue specimens paired with adjacent normal thyroid tissues were obtained from the Department of Surgical Oncology of Hangzhou First People’s Hospital from June-December 2011. miRNA expression profiles were examined by microarrays and validated by quantitative real-time PCR (qRT-PCR). Expression levels of the miRNAs were analyzed to assess if they were associated with selected clinicopathological features. Eleven miRNAs were significantly differentially expressed between nodular goiter and PTC and between highly invasive and low invasive PTC. miR-199b-5p and miR-30a-3p were significantly differentially expressed among the three groups. miR-30a-3p, miR-122-5p, miR-136-5p, miR-146b-5p and miR-199b-5p were selected for further study by qRT-PCR and miR-146b-5p, miR-199b-5p and miR-30a-3p were different between the PTC and nodular goiter groups. miR-199b-5p was over-expressed in PTC patients with extrathyroidal invasion and cervical lymph node metastasis. In conclusion miR-146b-5p, miR-30a-3p, and miR-199b-5p may serve as biomarkers for the diagnosis of PTC and miR-199b-5p is associated with PTC invasiveness. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

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16 pages, 3985 KiB

Open AccessArticle

miR-221/222 Promotes S-Phase Entry and Cellular Migration in Control of Basal-Like Breast Cancer

by Yuan Li, Chunli Liang, Haizhong Ma, Qian Zhao, Ying Lu, Zhendong Xiang, Li Li, Jie Qin, Yihan Chen, William C. Cho, Richard G. Pestell, Li Liang and Zuoren Yu

Molecules 2014, 19(6), 7122-7137; https://doi.org/10.3390/molecules19067122 - 30 May 2014

Cited by 74 | Viewed by 10389

Abstract

The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a [...] Read more.

The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC) cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both significantly suppressed cellular migration, invasion and G₁/S transition of the cell cycle in BLBC cell types. Proteomic analysis demonstrated the down-regulation of two tumor suppressor genes, suppressor of cytokine signaling 1 (SOCS1) and cyclin-dependent kinase inhibit 1B (CDKN1B), by miR-221/222. This is the first report to reveal miR-221/222 regulation of G₁/S transition of the cell cycle. These findings demonstrate that miR-221/222 contribute to the aggressiveness in control of BLBC. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

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12 pages, 319 KiB

Open AccessCommunication

Increased Circulating MicroRNA-155 as a Potential Biomarker for Breast Cancer Screening: A Meta-Analysis

by Faliang Wang, Jinchao Hou, Wei Jin, Jiaqiu Li, Yongfang Yue, Hongchuan Jin and Xian Wang

Molecules 2014, 19(5), 6282-6293; https://doi.org/10.3390/molecules19056282 - 16 May 2014

Cited by 37 | Viewed by 8292

Abstract

The objective of this meta-analysis was to determine the diagnostic accuracy of circulating microRNA-155 (miR-155) for breast cancer (BC). PubMed, Embase, EBSCO (ASP/BSP), Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched up to 30 January 2014 for eligible studies. Quality Assessment [...] Read more.

The objective of this meta-analysis was to determine the diagnostic accuracy of circulating microRNA-155 (miR-155) for breast cancer (BC). PubMed, Embase, EBSCO (ASP/BSP), Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched up to 30 January 2014 for eligible studies. Quality Assessment of Diagnostic Accuracy Studies (QUADAS) was employed to assess the quality of the included studies. Meta-analysis were performed in Meta-Disc 1.4 and Stata 12.0. Three studies with total 184 BC patients and 75 control individuals were included in this meta-analysis. All of the included studies are of high quality (QUADAS scores 12 or 13). The summary estimates revealed that the pooled sensitivity is 79% (95% confidence interval (CI): 72%–84%) and the specificity is 85% (95% CI: 75%–92%), for the diagnosis of breast cancer. In addition, the area under the summary ROC curve (AUC) is 0.9217. The current evidence suggests that circulating miR-155 has the potential diagnostic value with a high sensitivity and specificity for BC. More prospective studies on the diagnostic value of circulating miR-155 for BC are needed in the future. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

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13 pages, 200 KiB

Open AccessArticle

miRNAs for the Detection of MultiDrug Resistance: Overview and Perspectives

by Andreas Gisel, Mirna Valvano, Imane Ghafir El Idrissi, Patrizia Nardulli, Amalia Azzariti, Antonio Carrieri, Marialessandra Contino and Nicola Antonio Colabufo

Molecules 2014, 19(5), 5611-5623; https://doi.org/10.3390/molecules19055611 - 30 Apr 2014

Cited by 28 | Viewed by 7700

Abstract

The goal of the present paper is to establish and validate the link between cancer diagnosis and therapy by microRNAs detection. The induction in vitro of some specific microRNAs after treatment with MDR ligands has been outlined. Starting from the results obtained by [...] Read more.

The goal of the present paper is to establish and validate the link between cancer diagnosis and therapy by microRNAs detection. The induction in vitro of some specific microRNAs after treatment with MDR ligands has been outlined. Starting from the results obtained by in vitro induction of MDCK and MDCK-MDR1 cells treated by a MDR1 ligand, a new scenario in the early diagnosis and chemotherapy could be disclosed. To corroborate this perspective a short overview on pancreatic cancer diagnosis and chemotherapeutic treatment has been reported. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

17 pages, 481 KiB

Open AccessArticle

Assessment of Circulating microRNAs in Plasma of Lung Cancer Patients

by Orazio Fortunato, Mattia Boeri, Carla Verri, Davide Conte, Mavis Mensah, Paola Suatoni, Ugo Pastorino and Gabriella Sozzi

Molecules 2014, 19(3), 3038-3054; https://doi.org/10.3390/molecules19033038 - 10 Mar 2014

Cited by 66 | Viewed by 10939

Abstract

Lung cancer is the most common cause of cancer deaths worldwide and numerous ongoing research efforts are directed to identify new strategies for its early detection. The development of non-invasive blood-based biomarkers for cancer detection in its preclinical phases is crucial to improve [...] Read more.

Lung cancer is the most common cause of cancer deaths worldwide and numerous ongoing research efforts are directed to identify new strategies for its early detection. The development of non-invasive blood-based biomarkers for cancer detection in its preclinical phases is crucial to improve the outcome of this deadly disease. MicroRNAs (miRNAs) are a new promising class of circulating biomarkers for cancer detection and prognosis definition, but lack of consensus on data normalization methods for circulating miRNAs and the critical issue of haemolysis, has affected the identification of circulating miRNAs with diagnostic potential. We describe here an interesting approach for profiling circulating miRNAs in plasma samples based on the evaluation of reciprocal miRNA levels measured by quantitative Real-Time PCR. By monitoring changes of plasma miRNA-ratios, it is possible to assess the deregulation of tumor-related miRNAs and identify signatures with diagnostic and prognostic value. In addition, to avoid bias due to the release of miRNAs from blood cells, a miRNA-ratios signature distinguishing haemolyzed samples was identified. The method described was validated in plasma samples of lung cancer patients, but given its reproducibility and reliability, could be potentially applied for the identification of diagnostic circulating miRNAs in other diseases. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

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Review

Jump to: Research

14 pages, 204 KiB

Open AccessReview

MicroRNAs and Bone Metastasis: A New Challenge

by Martine Croset, Daniele Santini, Michele Iuliani, Marco Fioramonti, Alice Zoccoli, Bruno Vincenzi, Giuseppe Tonini and Francesco Pantano

Molecules 2014, 19(7), 10115-10128; https://doi.org/10.3390/molecules190710115 - 11 Jul 2014

Cited by 24 | Viewed by 7865

Abstract

The development of bone metastases requires multistep and multicellular machinery consisting not only of processes shared with any type of metastases (formation of a pre-metastatic niche, chemotaxis of tumor cells into the host tissue, tumor cells escape from the microvasculature), but also biological [...] Read more.

The development of bone metastases requires multistep and multicellular machinery consisting not only of processes shared with any type of metastases (formation of a pre-metastatic niche, chemotaxis of tumor cells into the host tissue, tumor cells escape from the microvasculature), but also biological interactions that are strictly related to the particular bone microenvironment (bone marrow colonization by cancer cells, osteomimicry, deregulation of bone homeostasis). MiRNAs are highly conserved, small RNAs molecules that regulate gene expression. The functional consequence of miRNA deregulation lies in the mRNA targets whose expression is altered. MiRNA networks acting as upstream regulators of these genes interfere with the initial steps of tumor local invasion and cancer cell intravasation, mainly by regulating the epithelial-mesenchymal transition, the motility, invasiveness and survival abilities of these cells. The miRNA-mediated regulation on the steps of bone tropism, anchorage, homing and finally bone colonization is more tissue specific, being dependent on the expression pattern of target miRNAs in bone marrow sinusoids, bone cells and microenvironment. In that, miRNA specific expression signatures that can distinguish between primary tumors from their corresponding bone metastases might be determinants of clinical aggressiveness. In this review, we focus on the current advances on functions and molecular mechanisms by which miRNAs exert their biological roles in regulating bone metastases development. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

18 pages, 214 KiB

Open AccessReview

miRNAs as Non-Invasive Biomarkers for Lung Cancer Diagnosis

by Paola Ulivi and Wainer Zoli

Molecules 2014, 19(6), 8220-8237; https://doi.org/10.3390/molecules19068220 - 17 Jun 2014

Cited by 56 | Viewed by 9047

Abstract

Lung cancer is a leading cause of cancer death and late diagnosis is one of the most important reasons for the high mortality rate. Circulating microRNAs (miRNAs) represent stable and reproducible markers for numerous solid tumors, including lung cancer, and have been hypothesized [...] Read more.

Lung cancer is a leading cause of cancer death and late diagnosis is one of the most important reasons for the high mortality rate. Circulating microRNAs (miRNAs) represent stable and reproducible markers for numerous solid tumors, including lung cancer, and have been hypothesized as non-invasive diagnostic markers. Serum, plasma or whole peripheral blood can be used as starting material, and several methodological approaches have been proposed to evaluate miRNA expression. The present review provides an in depth summary of current knowledge on circulating miRNAs in different types of biological samples used as diagnostic markers of lung cancer. We also evaluate the diagnostic accuracy of each miRNA or group of miRNAs in relation to the different housekeeping miRNAs used. Finally, the limitations and potential of miRNA analysis are discussed. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

20 pages, 281 KiB

Open AccessReview

Circulating miRNAs as Biomarkers for Neurodegenerative Disorders

by Margherita Grasso, Paola Piscopo, Annamaria Confaloni and Michela A. Denti

Molecules 2014, 19(5), 6891-6910; https://doi.org/10.3390/molecules19056891 - 23 May 2014

Cited by 174 | Viewed by 13231

Abstract

Neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and frontotemporal dementias (FTD), are considered distinct entities, however, there is increasing evidence of an overlap from the clinical, pathological and genetic points of view. All neurodegenerative diseases are characterized by neuronal loss [...] Read more.

Neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and frontotemporal dementias (FTD), are considered distinct entities, however, there is increasing evidence of an overlap from the clinical, pathological and genetic points of view. All neurodegenerative diseases are characterized by neuronal loss and death in specific areas of the brain, for example, hippocampus and cortex for AD, midbrain for PD, frontal and temporal lobes for FTD. Loss of neurons is a relatively late event in the progression of neurodegenerative diseases that is typically preceded by other events such as metabolic changes, synaptic dysfunction and loss, neurite retraction, and the appearance of other abnormalities, such as axonal transport defects. The brain’s ability to compensate for these dysfunctions occurs over a long period of time and results in late clinical manifestation of symptoms, when successful pharmacological intervention is no longer feasible. Currently, diagnosis of AD, PD and different forms of dementia is based primarily on analysis of the patient’s cognitive function. It is therefore important to find non-invasive diagnostic methods useful to detect neurodegenerative diseases during early, preferably asymptomatic stages, when a pharmacological intervention is still possible. Altered expression of microRNAs (miRNAs) in many disease states, including neurodegeneration, and increasing relevance of miRNAs in biofluids in different pathologies has prompted the study of their possible application as neurodegenerative diseases biomarkers in order to identify new therapeutic targets. Here, we review what is known about the role of miRNAs in the pathogenesis of neurodegeneration and the possibilities and challenges of using these small RNA molecules as a signature for neurodegenerative conditions. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

14 pages, 232 KiB

Open AccessReview

The role of Micro-RNAs in Hepatocellular Carcinoma: From Molecular Biology to Treatment

by Marco D'Anzeo, Luca Faloppi, Mario Scartozzi, Riccardo Giampieri, Maristella Bianconi, Michela Del Prete, Nicola Silvestris and Stefano Cascinu

Molecules 2014, 19(5), 6393-6406; https://doi.org/10.3390/molecules19056393 - 19 May 2014

Cited by 55 | Viewed by 8601

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third leading cause of cancer deaths. microRNAs (miRNAs) are evolutionary conserved small non-coding RNA that negatively regulate gene expression and protein translation. Recent evidences have shown that they are involved in [...] Read more.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third leading cause of cancer deaths. microRNAs (miRNAs) are evolutionary conserved small non-coding RNA that negatively regulate gene expression and protein translation. Recent evidences have shown that they are involved in many biological processes, from development and cell-cycle regulation to apoptosis. miRNAs can behave as tumor suppressor or promoter of oncogenesis depending on the cellular function of their targets. Moreover, they are frequently dysregulated in HCC. In this review we summarize the latest findings of miRNAs regulation in HCC and their role as potentially diagnostic and prognostic biomarkers for HCC. We highlight development of miRNAs as potential therapeutic targets for HCC. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

19 pages, 1727 KiB

Open AccessReview

MicroRNAs in Cervical Cancer: Evidences for a miRNA Profile Deregulated by HPV and Its Impact on Radio-Resistance

by Abraham Pedroza-Torres, Eduardo López-Urrutia, Verónica García-Castillo, Nadia Jacobo-Herrera, Luis A. Herrera, Oscar Peralta-Zaragoza, César López-Camarillo, David Cantú De Leon, Jorge Fernández-Retana, Jorge F. Cerna-Cortés and Carlos Pérez-Plasencia

Molecules 2014, 19(5), 6263-6281; https://doi.org/10.3390/molecules19056263 - 16 May 2014

Cited by 62 | Viewed by 16327

Abstract

Cervical carcinoma (CC) is one of the most common cancers and a leading cause of mortality in women worldwide. Epidemiologic and experimental data have clearly demonstrated a causal role of high-risk Human Papillomavirus (HR-HPV) types in CC initiation and progression, affecting the cellular [...] Read more.

Cervical carcinoma (CC) is one of the most common cancers and a leading cause of mortality in women worldwide. Epidemiologic and experimental data have clearly demonstrated a causal role of high-risk Human Papillomavirus (HR-HPV) types in CC initiation and progression, affecting the cellular processes by targeting and inactivating p53 and pRB host proteins. HR-HPV E5, E6 and E7 oncoproteins have the ability to deregulate several cellular processes, mostly apoptosis, cell cycle control, migration, immune evasion, and induction of genetic instability, which promote the accumulation of mutations and aneuploidy. In this scenario, genomic profiles have shown that aberrant expression of cellular oncogenic and tumor suppressive miRNAs have an important role in CC carcinogenesis. It has been stated that HPV infection and E6/E7 expression are essential but not sufficient to lead to CC development; hence other genetic and epigenetic factors have to be involved in this complex disease. Recent evidence suggests an important level of interaction among E6/E7 viral proteins and cellular miRNA, and other noncoding RNAs. The aim of the current review is to analyze recent data that mainly describe the interaction between HR-HPV established infections and specific cellular miRNAs; moreover, to understand how those interactions could affect radio-therapeutic response in tumor cells. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

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26 pages, 271 KiB

Open AccessReview

Issues and Prospects of microRNA-Based Biomarkers in Blood and Other Body Fluids

by John R. Chevillet, Inyoul Lee, Hilary A. Briggs, Yuqing He and Kai Wang

Molecules 2014, 19(5), 6080-6105; https://doi.org/10.3390/molecules19056080 - 14 May 2014

Cited by 104 | Viewed by 10133

Abstract

Cell-free circulating microRNAs (miRNAs) in the blood are good diagnostic biomarker candidates for various physiopathological conditions, including cancer, neurodegeneration, diabetes and other diseases. Since their discovery in 2008 as blood biomarkers, the field has expanded rapidly with a number of important findings. Despite [...] Read more.

Cell-free circulating microRNAs (miRNAs) in the blood are good diagnostic biomarker candidates for various physiopathological conditions, including cancer, neurodegeneration, diabetes and other diseases. Since their discovery in 2008 as blood biomarkers, the field has expanded rapidly with a number of important findings. Despite the initial optimistic views of their potential for clinical application, there are currently no circulating miRNA-based diagnostics in use. In this article, we review the status of circulating miRNAs, examine different analytical approaches, and address some of the challenges and opportunities. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

42 pages, 334 KiB

Open AccessReview

Significance and Therapeutic Value of miRNAs in Embryonal Neural Tumors

by Tarek Shalaby, Giulio Fiaschetti, Martin Baumgartner and Michael A. Grotzer

Molecules 2014, 19(5), 5821-5862; https://doi.org/10.3390/molecules19055821 - 6 May 2014

Cited by 13 | Viewed by 7134

Abstract

Embryonal tumors of the nervous system are the leading cause of childhood cancer-related morbidity and mortality. Medulloblastoma, supratentorial primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumor and neuroblastoma account for more than 20% of childhood malignancies and typify the current neural embryonal tumor model in [...] Read more.

Embryonal tumors of the nervous system are the leading cause of childhood cancer-related morbidity and mortality. Medulloblastoma, supratentorial primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumor and neuroblastoma account for more than 20% of childhood malignancies and typify the current neural embryonal tumor model in pediatric oncology. Mechanisms driving the formation of these tumors point towards impaired differentiation of neuronal and neuron-associated cells during the development of the nervous system as an important factor. The importance of microRNAs (miRNAs) for proper embryonic cell function has been confirmed and their aberrant expressions have been linked to tumor development. The role of miRNAs in controlling essential regulators of key pathways implicated in tumor development makes their use in diagnostics a powerful tool to be used for early detection of cancer, risk assessment and prognosis, as well as for the design of innovative therapeutic strategies. In this review we focus on the significance of miRNAs involved in the biology of embryonal neural tumors, delineate their clinical significance and discuss their potential as a novel therapeutic target. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

13 pages, 425 KiB

Open AccessReview

The Role of microRNA in Head and Neck Cancer: Current Knowledge and Perspectives

by Giulia Courthod, Pierfrancesco Franco, Loredana Palermo, Salvatore Pisconti and Gianmauro Numico

Molecules 2014, 19(5), 5704-5716; https://doi.org/10.3390/molecules19055704 - 5 May 2014

Cited by 33 | Viewed by 9921

Abstract

Head and neck cancer is one of the most commonly diagnosed malignancies worldwide. Patients with advanced disease stages frequently develop recurrences or distant metastasis, which results a five-year survival rates of less than 60% despite considerable advances in multimodality therapy. A better understanding [...] Read more.

Head and neck cancer is one of the most commonly diagnosed malignancies worldwide. Patients with advanced disease stages frequently develop recurrences or distant metastasis, which results a five-year survival rates of less than 60% despite considerable advances in multimodality therapy. A better understanding of molecular basis of tumorigenesis is required to improve clinical outcomes and to develop new anti-cancer drugs. microRNAs (miRNAs) are a class of small, non-coding, RNA molecules that modulate gene expression post-transcriptionally. They are important regulator in normal biological process; however miRNAs deregulation has been observed in many different tumors and is involved in tumorigenesis. miRNAs may act as tumor suppressors or as oncogenes. Several studies on head and neck cancer demonstrated how aberrant expression of miRNAs is involved in proliferation, metastasis, chemoresistence, and radioresistance. In addition, miRNAs are excellent biomarker targets because they circulate stable in human body fluids and can be obtained with non-invasive methods. Moreover, miRNAs up and down regulation has been correlated with specific cancer phenotype (poor prognosis, aggressiveness and resistance to treatment), playing a role as prognostic biomarkers. This review summarizes current finding on miRNAs in head and neck cancer and their potential role as target for next drug therapy. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

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23 pages, 293 KiB

Open AccessReview

Role of MicroRNA in Response to Ionizing Radiations: Evidences and Potential Impact on Clinical Practice for Radiotherapy

by Francesco Cellini, Alessio G. Morganti, Domenico Genovesi, Nicola Silvestris and Vincenzo Valentini

Molecules 2014, 19(4), 5379-5401; https://doi.org/10.3390/molecules19045379 - 24 Apr 2014

Cited by 62 | Viewed by 8936

Abstract

MicroRNAs (miRNA) are small, non-coding, RNAs with gene expression regulator roles. As an important class of regulators of many cellular pathways, miRNAs are involved in many signaling pathways and DNA damage repair processes, affecting cellular radiosensitivity. Their role has led to interest in [...] Read more.

MicroRNAs (miRNA) are small, non-coding, RNAs with gene expression regulator roles. As an important class of regulators of many cellular pathways, miRNAs are involved in many signaling pathways and DNA damage repair processes, affecting cellular radiosensitivity. Their role has led to interest in oncological implications to improve treatment results. MiRNAs represent a great opportunity to enhance the efficacy of radiotherapy treatments—they can be used to profile the radioresistance of tumors before radiotherapy, monitor their response throughout the treatment, thus helping to select intensification strategies, and also to define the final response to therapy along with risks of recurrence or metastatization. Even though many interesting studies support such potential, nowadays most studies on patient data are limited to experiments profiling tumor aggressiveness and response to radiotherapy. Moreover many studies report different although not conflicting results on the miRNAs evaluated for each tumor type. Without doubt, the clinical potential of such molecules for radiotherapy is striking and of high interest. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

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11 pages, 588 KiB

Open AccessReview

Clinical Application of MicroRNA Testing in Neuroendocrine Tumors of the Gastrointestinal Tract

by Caterina Vicentini, Matteo Fassan, Edoardo D'Angelo, Vincenzo Corbo, Nicola Silvestris, Gerard J. Nuovo and Aldo Scarpa

Molecules 2014, 19(2), 2458-2468; https://doi.org/10.3390/molecules19022458 - 21 Feb 2014

Cited by 52 | Viewed by 10404

Abstract

It is well documented that dysregulation of microRNAs is a hallmark of human cancers. Thus, this family of small non-coding regulatory molecules represents an excellent source of sensitive biomarkers. Unique microRNAs expression profiles have been associated with different types and subsets of gastrointestinal [...] Read more.

It is well documented that dysregulation of microRNAs is a hallmark of human cancers. Thus, this family of small non-coding regulatory molecules represents an excellent source of sensitive biomarkers. Unique microRNAs expression profiles have been associated with different types and subsets of gastrointestinal tumors including gastroenteropancreatic neuroendocrine tumors (GEP-NETs). GEP-NETs are a heterogeneous group of epithelial neoplasms with neuroendocrine differentiation. At present, early detection and surgical resection of GEP-NETs represent the best chance for a cure. Thus, clinically useful biomarkers for GEP-NETs that strongly correlate with early detection are urgently needed. The purpose of this review is to summarize the role of miRNAs in GEP-NET carcinogenesis and their possible use as novel diagnostic, prognostic and predictive biomarkers. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

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27 pages, 308 KiB

Open AccessReview

Tumor-Associated Circulating MicroRNAs as Biomarkers of Cancer

by Jin Wang, Ke-Yong Zhang, Song-Mei Liu and Subrata Sen

Molecules 2014, 19(2), 1912-1938; https://doi.org/10.3390/molecules19021912 - 10 Feb 2014

Cited by 149 | Viewed by 13179

Abstract

MicroRNAs (miRNAs), the 17- to 25-nucleotide long noncoding RNAs that modulate the expression of mRNAs and proteins, have emerged as critical players in cancer initiation and progression processes. Deregulation of tissue miRNA expression levels associated with specific genetic alterations has been demonstrated in [...] Read more.

MicroRNAs (miRNAs), the 17- to 25-nucleotide long noncoding RNAs that modulate the expression of mRNAs and proteins, have emerged as critical players in cancer initiation and progression processes. Deregulation of tissue miRNA expression levels associated with specific genetic alterations has been demonstrated in cancer, where miRNAs function either as oncogenes or as tumor-suppressor genes and are shed from cancer cells into circulation. The present review summarizes and evaluates recent advances in our understanding of the characteristics of tumor tissue miRNAs, circulating miRNAs, and the stability of miRNAs in tissues and their varying expression profiles in circulating tumor cells, and body fluids including blood plasma. These advances in knowledge have led to intense efforts towards discovery and validation of differentially expressing tumor-associated miRNAs as biomarkers and therapeutic targets of cancer. The development of tumor-specific miRNA signatures as cancer biomarkers detectable in malignant cells and body fluids should help with early detection and more effective therapeutic intervention for individual patients. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

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