MicroRNA in pancreatic adenocarcinoma: predictive/prognostic biomarkers or therapeutic targets?

Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a poor prognosis, short overall survival and few chemotherapeutic choices. MicroRNAs (miRNAs) are non-coding, single-stranded RNAs of around 22 nucleotides involved in the pathogenic mechanisms of carcinogenesis and metastasis. They have been studied in many tumors in order to identify potential diagnostic, prognostic or therapeutic targets. In the current literature, many studies have analyzed the role of miRNAs in PDAC. In fact, the absence of appropriate biomarkers, the difficultly of early detection of this tumor, and the lack of effective chemotherapy in patients with unresectable disease have focused attention on miRNAs as new, interesting advance in this malignancy.In this review we analyzed the role of miRNAs in PDAC in order to understand the mechanisms of action and the difference between the onco-miRNA and the tumor suppressor miRNA. We also reviewed all the data related to the use of these molecules as predictive as well as prognostic biomarkers in the course of the disease.Finally, the possible therapeutic use of miRNAs or anti-miRNAs in PDAC is also discussed.In conclusion, although there is still no clinical application for these molecules in PDAC, it is our opinion that the preclinical evidence of the role of specific miRNAs in carcinogenesis, the possibility of using miRNAs as diagnostic or prognostic biomarkers, and their potential therapeutic role, warrant future studies in PDAC.     

miRNA expression profiles associated with diagnosis and prognosis in lung cancer

miRNAs, which are small single-stranded RNA molecules composed of 18–23 nts, act as oncogenes or tumor suppressor genes playing important roles in the processes of tumor formation, infiltration and metastasis. Lung cancer currently has the highest morbidity and mortality among all malignant tumors; yet, lack of early specific diagnostic markers and effective treatments hinders its proper management. In lung cancer, about 40–45 abnormal expression patterns of miRNAs have been discovered and are involved in lung cancer development. miRNAs have functions together with oncogenes and tumor suppressor genes of lung cancer. miRNAs-based tests can be used for early clinical diagnosis and prediction of clinical outcomes of lung cancer. Studying the role of miRNAs in lung cancer development and its relationship with diagnostic and prognostic parameters might help to improve the sensitivity of diagnosis and the efficacy of lung cancer treatment.     

Role of miRNA in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Evidence suggests that miRNAs play an important role in progression, recurrence, metastasis and postoperative survival of HNSCC. Studies have investigated the utility of miRNAs as diagnostic/prognostic tools and as potential therapeutic targets and biomarkers that may improve the management and outcomes of HNSCC. The aim of this article is to review the current literature on aberrant expression profiles of miRNAs in biopsy samples of HNSCC and their role in cancer development, metastasis, prognosis and survival of these patients. This review gives an overview that miRNAs deregulation play major role in the development of HNSCC. They offer the potential to be used as biomarkers or novel therapeutic targets. Future research is required to test their use in both of these fields.     

microRNAs in breast cancer development and treatment

microRNAs (herein after miRNAs) represent a recently uncovered class of small and endogenous non-coding RNAs. miRNAs play a well conserved and crucial role in normal biological processes, such as cell differentiation, proliferation and apoptosis through a complicated gene regulation networking. The recent rise of interest in miRNAs in cancer research is ascribed to the breakthrough of their role in many pathological processes, including malignant transformation. miRNAs signatures have been clearly defined for certain types of cancer, with correlation to tumor aggressiveness, therapy response and patient outcome. Furthermore, the use of miRNAs as therapeutic targets for cancer is currently under investigation. The aim of this review is to focus on the role of miRNAs in breast cancer development and to summarize the evidence for their potential diagnostic and therapeutic applications in clinical practice.     

MicroRNA dysregulation in colorectal cancer: a clinical perspective

Recent researches have shed light on the biological importance of microRNAs (miRNAs) in colorectal cancer (CRC) genesis, progression and response to treatments. The potential utility of miRNAs in the preclinical stage have been explored and investigated. In this review, we explored the literature and reviewed the cutting edge progress in the discovery of noninvasive plasma and faecal miRNAs for CRC early diagnosis, as well as their measurability and predictability. We also discussed the utility of miRNAs as novel prognostic and predictive markers, and their association with CRC clinical phenotypes including recurrence, metastasis and therapeutic outcomes. Finally, we summarised miRNA-related single-nucleotide polymorphisms and their potential influence on sporadic CRC susceptibility and therapeutic response. In conclusion, the use of miRNAs as biomarker for CRC is still in its infancy and need further characterisation and evaluation.     

Exploring circulating micro‐RNA in the neoadjuvant treatment of breast cancer

Breast cancer is the most frequently diagnosed malignancy amongst females worldwide. In recent years the management of this disease has transformed considerably, including the administration of chemotherapy in the neoadjuvant setting. Aside from increasing rates of breast conserving surgery and enabling surgery via tumour burden reduction, use of chemotherapy in the neoadjuvant setting allows monitoring of in vivo tumour response to chemotherapeutics. Currently, there is no effective means of identifying chemotherapeutic responders from non‐responders. Whilst some patients achieve complete pathological response (pCR) to chemotherapy, a good prognostic index, a proportion of patients derive little or no benefit, being exposed to the deleterious effects of systemic treatment without any knowledge of whether they will receive benefit. The identification of predictive and prognostic biomarkers could confer multiple benefits in this setting, specifically the individualization of breast cancer management and more effective administration of chemotherapeutics. In addition, biomarkers could potentially expedite the identification of novel chemotherapeutic agents or increase their efficacy. Micro‐RNAs (miRNAs) are small non‐coding RNA molecules. With their tissue‐specific expression, correlation with clinicopathological prognostic indices and known dysregulation in breast cancer, miRNAs have quickly become an important avenue in the search for novel breast cancer biomarkers. We provide a brief history of breast cancer chemotherapeutics and explore the emerging field of circulating (blood‐borne) miRNAs as breast cancer biomarkers for the neoadjuvant treatment of breast cancer. Established molecular markers of breast cancer are outlined, while the potential role of circulating miRNAs as chemotherapeutic response predictors, prognosticators or potential therapeutic targets is discussed.     

miRNA-181家族与恶性肿瘤关系的研究进展

近年来microRNA-181(miR-181)家族已经成为生物医学界所关注的热点之一。许多研究表明，多种恶性肿瘤（肝癌、胃癌、乳腺癌、胰腺癌、肺癌、胶质瘤、白血病等）中miR-181家族表达异常。目前已证实miR-181家族存在众多靶点，miR-181家族作用于其各自的靶点，进而调控恶性肿瘤细胞的增殖、分化、凋亡、侵袭、转移，以及参与恶性肿瘤的耐药等，miR-181家族已经成为众多恶性肿瘤的新型诊断标志物及治疗的靶点。     

The expression and functions of microRNAs in pancreatic adenocarcinoma and hepatocellular carcinoma

Pancreatic adenocarcinoma and hepatocellular carcinoma are devastating human malignancies that are characterized by poor prognosis, late onset, and a lack of known biomarkers. New diagnostic and therapeutic molecular targets are desperately needed to develop novel and effective treatment strategies. MicroRNAs (miRNAs) are an emerging class of molecules with roles in various cellular processes, including growth, survival, and apoptosis. Most importantly, aberrant expression of miRNAs has been implicated in cancer pathogenesis. miRNA expression profiles of pancreatic adenocarcinoma and hepatocellular carcinoma indicate selective overexpression of oncogenic miRNAs and down-regulation of tumor suppressive miRNAs in these cancers. This review summarizes results from key studies conducted to characterize the miRNA expression profiles of pancreatic adenocarcinoma and hepatocellular carcinoma and describes the potential mechanisms by which some oncogenic or tumor suppressive miRNAs act. Furthermore, this review outlines novel therapeutic strategies for targeting miRNAs.     

MicroRNAs

MicroRNAs (miRNAs) are small, noncoding RNAs with regulatory functions, which play an important role in many human diseases, including cancer. An emerging number of studies show that miRNAs can act either as oncogenes or as tumor suppressor genes or sometimes as both. Germline, somatic mutations and polymorphisms can contribute to cancer predisposition. miRNA expression levels have diagnostic and prognostic implications, and their roles as anticancer therapeutic agents is promising and currently under investigation.     

Dysregulation of microRNAs in breast cancer and their potential role as prognostic and predictive biomarkers in patient management

MicroRNAs (miRNAs) are an emerging class of gene expression modulators with relevant roles in several biological processes, including cell differentiation, development, apoptosis, and regulation of the cell cycle. Deregulation of those tiny RNA molecules has been described frequently as a major determinant for the initiation and progression of diseases, including cancer. Not only miRNAs but also the enzymes responsible for miRNA processing could be deregulated in cancer. In this review, we address the role of miRNAs in the pathogenesis of breast cancer, since there are oncogenic, tumor-suppressive, and metastatic-influencing miRNAs. Additionally, the different detection platforms and normalization strategies for miRNAs will be discussed. The major part of this review, however, will focus on the capability of miRNAs to act as diagnostic, predictive, or prognostic biomarkers. We will give an overview of their potential to correlate with response to or benefit from a given treatment and we will consider their ability to give information on prognosis in breast cancer. We will focus on miRNAs validated by more than one study or verified in independent cohorts or where results rely on preclinical as well as clinical evidence. As such, we will discuss their potential use in the personalized management of breast cancer.     

Current research on circular RNAs and their potential clinical implications in breast cancer

Breast cancer (BC) is one of the most common cancers and the leading causes of death among women worldwide, and its morbidity rate is growing. Discovery of novel biomarkers is necessary for early BC detection, treatment, and prognostication. Circular RNAs (circRNAs), a novel type of endogenous non-coding RNAs with covalently closed continuous loops, have been found to have a crucial role in tumorigenesis. Studies have demonstrated that circRNAs are aberrantly expressed in the tumor tissues and plasma of patients with BC, and they modulate gene expression affecting the proliferation, metastasis, and chemoresistance of BC by specifically binding and regulating the expression of microRNAs (miRNAs). Therefore, circRNAs can be used as novel potential diagnostic and prognostic markers, and therapeutic targets for BC. This article summarizes the properties, functions, and regulatory mechanisms of circRNAs, particularly current research on their association with BC proliferation, metastasis, and chemoresistance.     

Clinical implications of microRNAs in lung cancer

Lung cancer still represents a very deadly disease in strong need of new, effective, therapeutic approaches. MicroRNAs (miRNAs) represent a new category of noncoding RNAs with gene expression regulatory functions. Several studies have shown that miRNAs are frequently deregulated in lung cancer patients with respect to healthy individuals. These aberrations of the miRNome (defined as the full spectrum of miRNAs in a given genome) occur at several levels, including primary tumors and patient body fluids (such as blood and sputum), suggesting that miRNAs can be effectively used as biological markers with diagnostic, prognostic, and predictive implications. This review focuses on these translational aspects of research on the field of miRNAs and lung cancer.     

环状RNA在肿瘤疾病中的研究进展

环状RNA是一种新型RNA,在生物体中具有microRNA“海绵”、RNA结合蛋白及核转录调节等功能。在肿瘤疾病中,环状RNA主要以miRNA“海绵”的形式发挥调控作用,促进或抑制肿瘤的发生和发展。此外,环状RNA还可以作为肿瘤早期诊断、预后评估的生物标记物,也可作为抗肿瘤治疗的靶标,具有潜在的临床诊断治疗价值。本文就环状RNA在肿瘤疾病中的作用机制及临床应用进行综述。      

MicroRNA-21: a novel therapeutic target in human cancer

Resistance to anticancer agents is the major clinical obstacle to the successful treatment of cancer, yet the mechanisms underlying drug resistance have not been fully characterized. MicroRNAs (miRNAs) are endogenous, small (19-25 nucleotides in length) noncoding RNAs, which function by base pairing with messenger RNAs, thereby regulating protein expression. Emerging evidence shows that alteration of miRNAs is involved in cancer initiation and progression. MiR-21 is a miRNA that is overexpressed in most tumor types, and acts as an oncogene by targeting many tumor suppressor genes related to proliferation, apoptosis, and invasion. In vivo and in vitro studies suggest that miR-21 may serve as a diagnostic and prognostic marker for human malignancies. More recently, studies have identified an important role for miR-21 in anticancer drug resistance. Here, we review the mechanisms underlying miR-21-mediated chemoresistance and the potential use of miR-21 as a novel molecular target for cancer chemotherapy.     

miRNAs as biomarkers in prostate cancer

Current prostate cancer (PCa) diagnosis is based in the serum prostate-specific antigen biomarker and digital rectal examination. However, these methods are limited by a low predictive value (24?C37?%) and a high risk of mistaken results. During last years, new promising biomarkers such as Prostate Cancer Antigen 3 (PCA-3) and TMPRSS2-ETS fusion genes have been evaluated for their clinical use. However, the search of new biomarkers that could be used for PCa diagnosis and prognosis is still needed. Recent studies have demonstrated that the aberrant expression of microRNAs (miRNAs), small non-coding RNAs that negatively regulate gene expression, is related with the development of several cancers, including PCa. Since miRNAs serve as phenotypic signatures of different cancers, they appear as potential diagnostic, prognostic and therapeutic tools. Here, we review the current knowledge of miRNA expression patterns in PCa and their role in PCa prognosis and therapeutics.     

Serum microRNAs as potential noninvasive biomarkers for glioma

Gliomas are derived from astroglial precursors or astrocytes, accounting for 40 % central nervous system tumors. MicroRNAs (miRNAs) are a class of endogenous, small (19- to 23-nucleotides) non-coding RNAs involved in cancer progression. Recent studies show that circulating miRNAs are associated with the clinicopathological features and prognosis of gliomas. Serum miRNAs may serve as novel biomarkers for gliomas diagnosis. This review explores the possibilities of using serum miRNAs as prognostic, diagnostic markers, and therapeutic targets in gliomas.