MicroRNAs (miRNAs) are a class of small noncoding RNAs, which function in posttranscriptional regulation of gene expression. They are powerful regulators of various cellular activities including cell growth, differentiation, development, and apoptosis. They have been linked to many diseases, and currently miRNA-mediated clinical trial has shown promising results for treatment of cancer and viral infection. This review provides an overview and update on miRNAs biogenesis, regulation of miRNAs expression, their biological functions, and role of miRNAs in epigenetics and cell-cell communication. In addition, alteration of miRNAs following exercise, their association with diseases, and therapeutic potential will be explained. Finally, miRNA bioinformatics tools and conventional methods for miRNA detection and quantification will be discussed.

An overview of microRNAs: Biology, functions, therapeutics, and analysis methods

Collagen is the major component of the tumor microenvironment and participates in cancer fibrosis. Collagen biosynthesis can be regulated by cancer cells through mutated genes, transcription factors, signaling pathways and receptors; furthermore, collagen can influence tumor cell behavior through integrins, discoidin domain receptors, tyrosine kinase receptors, and some signaling pathways. Exosomes and microRNAs are closely associated with collagen in cancer. Hypoxia, which is common in collagen-rich conditions, intensifies cancer progression, and other substances in the extracellular matrix, such as fibronectin, hyaluronic acid, laminin, and matrix metalloproteinases, interact with collagen to influence cancer cell activity. Macrophages, lymphocytes, and fibroblasts play a role with collagen in cancer immunity and progression. Microscopic changes in collagen content within cancer cells and matrix cells and in other molecules ultimately contribute to the mutual feedback loop that influences prognosis, recurrence, and resistance in cancer. Nanoparticles, nanoplatforms, and nanoenzymes exhibit the expected gratifying properties. The pathophysiological functions of collagen in diverse cancers illustrate the dual roles of collagen and provide promising therapeutic options that can be readily translated from bench to bedside. The emerging understanding of the structural properties and functions of collagen in cancer will guide the development of new strategies for anticancer therapy.

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The role of collagen in cancer: from bench to bedside

MicroRNAs (miRNAs) are endogenous non-coding small RNA molecules that can be secreted into the circulation and exist in remarkably stable forms. Like intercellular miRNAs, circulating miRNAs participate in numerous regulations of biological process and expressed aberrantly under abnormal or pathological status. The quality and quantity changes of circulating miRNAs are associated with the initiation and progression of cancer and can be easily detected by basic molecular biology techniques. Consequently, considerable effort has been devoted to identify suitable extracellular miRNAs for noninvasive biomarkers in cancer. However, several challenges need to be overcome before the practical application. In this review, we discuss several issues of circulating miRNAs: biological function and basic transport carriers; extracellular cell communication process; roles as reliable cancer biomarkers and usage in targeted cancer therapy; and challenges for clinical application.

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Circulating MicroRNAs in Cancer: Potential and Challenge

Esophageal cancer is a common malignant tumor with an increasing trend during the past three decades. Currently, esophagectomy, often in combination with neoadjuvant chemo- and radiotherapy, is the cornerstone of curative treatment for esophageal cancer. However, esophagostomy is related to significant risks of perioperative mortality and morbidity, as well as lengthy recovery. Moreover, the adjuvant therapies including chemotherapy and radiotherapy are associated with numerous side effects, limiting compliance and outcome. The dietary agent curcumin has been extensively studied over the past few decades and is known to have many biological activities especially in regard to the prevention and potential treatment of cancer. This review summarizes the chemo-preventive and chemotherapeutic potential of curcumin in esophageal cancer in both preclinical and clinical settings.

Chemopreventive and therapeutic potential of curcumin in esophageal cancer: Current and future status.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide Its main neuropathological hallmarks are the degeneration of dopaminergic neurons in the substantia nigra and alpha-synuclein containing protein inclusions, called Lewy Bodies The diagnosis of idiopathic PD is still based on the assessment of clinical criteria, leading to an insufficient diagnostic accuracy Additionally, there is no biomarker available allowing the prediction of the disease course or monitoring the response to therapeutic approaches So far, protein biomarker candidates such as alpha-synuclein have failed to improve diagnosis of PD Circulating microRNAs (miRNAs) in body fluids are promising biomarker candidates for PD, as they are easily accessible by non- or minimally-invasive procedures and changes in their expression are associated with pathophysiological processes relevant for PD Advances in miRNA analysis methods resulted in numerous recent publications on miRNAs as putative biomarkers Here, we discuss the applicability of different body fluids as sources for miRNA biomarkers, highlight technical aspects of miRNA analysis and give an overview on published studies investigating circulating miRNAs as biomarker candidates for diagnosis of PD and other Parkinsonian syndromes

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Circulating miRNAs as Diagnostic Biomarkers for Parkinson’s Disease

Gastric and esophageal cancers are as main cancers of the gastrointestinal (GI) tract, which are associated with poor diagnosis and survival. Several efforts were made in the past few decades to finding effective therapeutic approaches, but these approaches had several problems. Finding new biomarkers is a critical step in finding new approaches for the treatment of these cancers. Finding new biomarkers that cover various aspects of the diseases could provide a choice of suitable therapies and better monitoring of patients with these cancers. Among several biomarkers tissue specific and circulating microRNAs (miRNAs) have emerged as powerful candidates in the diagnosis of gastric and esophageal cancers. MiRNAs are small noncoding single-stranded RNA molecules that are found in the blood and regulate gene expression. These have numerous characteristics that make them suitable for being used as ideal biomarkers in cancer diagnosis. Research has indicated that the level and profile of miRNA in serum and plasma are very high. They are potentially noninvasive and sensitive enough to detect tumors in their primary stages of infection. Multiple lines of evidence indicate that the presence, absence, or deregulation of several circulating miRNAs (i.e., let-7a, miR-21, miR-93, miR-192a, miR-18a, and miR-10b for gastric cancer, and miR-21, miR-375, miR-25-3p, miR-151a-3p, and miR-100-3p for esophageal cancer) are associated with initiation and progression of gastric and esophageal cancers. The aim of this review is to highlight the recent advances in the roles of miRNAs in diagnosis and treatment of gastric and esophageal cancers.

Circulating microRNAs as diagnostic and therapeutic biomarkers in gastric and esophageal cancers

Background: Cofilin-1 (CLF1) and scinderin (SCIN) are significant actin-binding proteins that are involved in the regulation of the actin polymerization dynamics. Overexpression of CLF1 and SCIN has been associated with aggressive and tumorigenesis characteristics of various cancer types. The aim of the present study was to investigate the expression of CFL1 and SCIN genes in breast cancer cells and their association with clinicopathological features. Materials and Methods: In this study, 65 breast cancer tissues were randomly selected, and quantitative real-time polymerase chain reaction was performed to measure the expression level of CFL1 and SCIN genes in breast tumors. Then, the association of CFL1 and SCIN expression level with clinicopathological features was assessed using Prism 5 software. Results: Overexpression of CFL1 and SCIN was observed to be statistically significantly associated with tumor stage and lymph node involvement (P

Expression patterns of cofilin and scinderin in breast cancer and their association with clinicopathological features in Iranian patients

Background: Breast cancer is the most common type of cancer among women, and is among the five most prevalent cancer types among Iranian women. Advanced-stage breast cancer is often correlated with distant metastases. Alterations in gene expression affect general cytoskeleton changes during differentiation and oncogenesis, and can be considered an important factor in tumor progression. Gelsolin plays a significant role in actin assembly and has been introduced as a tumor activator. The aim of this study was to evaluate the expression of Gelsolin in breast cancer as well as its correlation with patients’ clinical parameters. Methods: In this study, 70 breast cancer patients, who had been referred to Cancer Institute, Imam Khomeini Hospital Complex for surgery were randomly selected. Normal and tumor tissues were prepared and stored at -80°C. Gelsolin gene expression was measured using real-time polymerase chain reaction (PCR). Results: The results showed that Gelsolin gene expression had increased in 68.6% of the tumor samples. In addition, there was a significant association between increased levels of gene expression and tumor progression stages (P < 0.05). However, there was no significant association between increased levels of gene expression and other clinical findings, such as tumor grade, tumor size or patient age. Conclusion: The results revealed that Gelsolin gene expression had increased in the tumor samples. Gelsolin overexpression also resulted in increased lymph node involvement in breast cancer. The expression of this gene also increased significantly during advanced stages of breast cancer; however, there was no significant relation between Gelsolin expression and tumor grade or tumor size.

Parisa Nourmohammadi

Papers

Circulating microRNAs as diagnostic and therapeutic biomarkers in gastric and esophageal cancers

Expression patterns of cofilin and scinderin in breast cancer and their association with clinicopathological features in Iranian patients

Evaluating Gelsolin Gene Expression Among Iranian Breast Cancer Patients