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Glioblastoma multiforme (GBM), a solid tumor that develops from astrocytes, is one of the most aggressive types of brain cancer. While there have been improvements in the efficacy of treating GBM, many problems remain, especially with traditional therapy methods. Therefore, recent studies have extensively focused on developing novel therapeutic agents for combating glioblastoma. Natural polyphenols have been studied for their potential as chemopreventive and chemotherapeutic agents due to their wide range of positive qualities, including antioxidant, antiinflammatory, cytotoxic, antineoplastic, and immunomodulatory activities. These natural compounds have been suggested to act via modulated various macromolecules within cells, including microRNAs (miRNAs), which play a crucial role in the molecular milieu. In this article, we focus on how polyphenols may inhibit tumor growth by influencing the expression of key miRNAs that regulate oncogenes and tumor suppressor genes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Although there have been significant advancements in cancer treatment, resistance and recurrence in patients make it one of the leading causes of death worldwide. 5-fluorouracil (5-FU), an antimetabolite agent, is widely used in treating a broad range of human malignancies. The cytotoxic effects of 5-FU are mediated by the inhibition of thymidylate synthase (TYMS/TS), resulting in the suppression of essential biosynthetic activity, as well as the misincorporation of its metabolites into RNA and DNA. Despite its huge benefits in cancer therapy, the application of 5-FU in the clinic is restricted due to the occurrence of drug resistance. MicroRNAs (miRNAs) are small, non-coding RNAs that act as negative regulators in many gene expression processes. Research has shown that changes in miRNA play a role in cancer progression and drug resistance. This review examines the role of miRNAs in 5-FU drug resistance in cancers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The third most common malignancy has been identified as Colorectal cancer (CRC) that conducive to death in most cases. Chemoresistance is a common obstacle to CRC treatment. Circulating exosomal microRNAs (miRNAs) have been shown to reverse chemo-resistance and are promising biomarkers for CRC. The capacity of engineered exosomes to cross biological barriers and deliver functional miRNAs could be used to achieve these proposes. The object of this review is the investigation of the role of exosomal miRNA in the chemo-resistance, diagnosis, and prognosis of CRC. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, electronic databases, PubMed, EMBASE, Web of Science, Scopus were searched from January 1990 to November 2020. Ultimately, eight articles included five in vitro (16 cell lines) and three in vivo examinations. Three studies demonstrated that increasing or decreasing mRNA expression was associated with increasing and decreasing cell proliferation in vitro. The presence of miRNA in two studies increased the sensitivity of the drug and exhibited a considerable growth inhibitory effect on cancer cell proliferation. The apoptotic rate was significantly increased in four studies by increased mRNA expression and reduced mrna expression. Tumor volume of xenograft models in three studies suppressed by antitumor miRNA activity. In contrast, anti-miRNA activity in one study decreased the tumor volume. Exosomal miRNAs can be regulators of chemo-resistance and predict adverse outcomes in CRC patients. In sum, exosomes containing miRNAs can be a promising biomarker for the prognosis and diagnosis of CRC. Subsequent research should be a focus on delineating the function of exosomal miRNA before clinical use., (© 2021 John Wiley & Sons Ltd.)

Background: Osteosarcoma (OS) patients are commonly treated with chemotherapeutic agents like cisplatin (Cis). Quercetin with fewer side effects can improve the potency of chemotherapy and be used in combinational therapies. Herein, we aimed to evaluate the effects of Cis plus quercetin on DNA damage response (DDR), DNA repair, and apoptosis in Saos-2 cells., Methods: The effects of Cis and quercetin single or in combination on Saos-2 cell viability and the cytotoxicity of the drugs were measured by MTT assay. The expression of DDR and repair components including P53, ATM, ATR, RAD51, and H2AX, and also miR-22 were analyzed by real-time PCR. The rate of apoptosis was measured by flow cytometry., Results: Quercetin potentiated the cytotoxic effects of Cis in Saos-2 cells. The IC50 of Cis reduced from 6.12 µM to 4.25 µM. The combination of quercetin and Cis was associated with the up-regulation of miR-22 and DDR components, including P53, ATM, ATR, and H2AX as well as the down-regulation of RAD51. Moreover, this combined regimen significantly induced apoptosis in Saos-2 cells compared to mono drugs., Conclusion: The co-treatment of quercetin and Cis can accelerate DNA damage, DNA damage response, and apoptosis while interfering with the DNA repair process in Saos-2 cells. Moreover, this combination provokes the tumor suppressor miR-22 expression in these cells., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Phosphoinositide-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway is one of the most important proliferative signaling pathways with critical undeniable function in various aspects of cancer initiation/progression, including proliferation, apoptosis, metastasis, angiogenesis, and drug resistance. On the other hand, numerous genetic alterations in the key genes involved in the PI3K/AKT/mTOR signaling pathway have been identified in multiple solid and hematological tumors. In addition, accumulating recent evidences have demonstrated a reciprocal interaction between this signaling pathway and microRNAs, a large group of small non-coding RNAs. Therefore, in this review, it was attempted to discuss about the interaction between key components of PI3K/AKT/mTOR signaling pathway with various miRNAs and their importance in cancer biology., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Telomerase is a nucleoprotein reverse transcriptase that maintains the telomere, a protective structure at the ends of the chromosome, and is active in cancer cells, stem cells, and fetal cells. Telomerase immortalizes cancer cells and induces unlimited cell division by preventing telomere shortening. Immortalized cancer cells have unlimited proliferative potential due to telomerase activity that causes tumorigenesis and malignancy. Therefore, telomerase can be a lucrative anti-cancer target. The regulation of catalytic subunit of telomerase (TERT) determines the extent of telomerase activity. miRNAs, as an endogenous regulator of gene expression, can control telomerase activity by targeting TERT mRNA. miRNAs that have a decreasing effect on TERT translation mediate modulation of telomerase activity in cancer cells by binding to TERT mRNA and regulating TERT translation. In this review, we provide an update on miRNAs that influence telomerase activity by regulation of TERT translation., (Copyright © 2020. Published by Elsevier Inc.)

Background: Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies with a significant mortality rate. Despite the great advances in cancer treatment in the last few decades, effective treatment of CRC is still under challenge. One of the main problems associated with CRC treatment is the resistance of cancer cells to chemotherapy drugs., Methods: Many studies have been carried out to identify CRC chemoresistance mechanisms, and shed light on the role of ATP-binding cassette transporters (ABC transporters), enzymes as thymidylate synthase, some signaling pathways, and cancer stem cells (CSC) in chemoresistance and failed CRC chemotherapies. Other studies have also been recently carried out to find solutions to overcome chemoresistance. Some of these studies have identified the role of miRNAs in chemoresistance of the CRC cells and the effective use of these micro-molecules to CRC treatment., Results: Considering the results of these studies, more focus on miRNAs likely leads to a proper solution to overcome CRC chemoresistance., Conclusion: The current study has reviewed the related literature while discussing the efficacy of miRNAs as potential clinical tools for overcoming CRC chemoresistance and reviewing the most important chemoresistance mechanisms in CRC cells., Competing Interests: Declaration of competing interest The authors declare that there are no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Breast cancer is one of the most lethal malignancies in women in the world. Various factors are involved in the development and promotion of the malignancy; most of them involve changes in the expression of certain genes, such as microRNAs (miRNAs). MiRNAs can regulate signaling pathways negatively or positively, thereby affecting tumorigenesis and various aspects of cancer progression, particularly breast cancer. Besides, accumulating data demonstrated that miRNAs are a novel tool for prognosis and diagnosis of breast cancer patients. Herein, we will review the roles of these RNA molecules in several important signaling pathways, such as transforming growth factor, Wnt, Notch, nuclear factor-κ B, phosphoinositide-3-kinase/Akt, and extracellular-signal-regulated kinase/mitogen activated protein kinase signaling pathways in breast cancer., (© 2019 Wiley Periodicals, Inc.)

Ageing is a multifactorial and integrated gradual deterioration affecting the most of biological process of cells. MiRNAs are differentially expressed in the cellular senescence and play important role in regulating of genes expression involved in features of ageing. The perception of miRNAs functions in ageing regulation can be useful in clarifying the mechanisms underlying ageing and designing of therapeutic strategies. The preservation of genomic integrity through DNA damage response (DDR) is related to the process of cellular senescence. The recent studies have shown that miRNAs has directly regulated the expression of numerous proteins in DDR pathways. In this review study, DDR pathways, miRNA biogenesis and functions, current finding on DDR regulations, molecular biology of ageing and the role of miRNAs in these processes have been studied. Finally, a brief explanation about the therapeutic function of miRNAs in ageing regarding its regulation of DDR has been provided.

Regarding the importance of genetic and epigenetic factors in regulation of aging process, different expression pattern of non-coding RNAs in aging could be investigated. Accordingly, micro RNAs (miRNAs) with a wide range of physiological functions as well as a significant footprint in many diseases have been demonstrated to be down or upregulated during the aging process. Therefore, age-associated microRNAs and their targets have potentially detected the accelerated aging and predicted the risks for age-related diseases. Polyphenols as important antioxidants in human dietary observed in fruits and some beverages have beneficial effects on longevity and aging. Considering miRNAs as an interesting mediator in modulating polyphenols' biological effects, targeting miRNAs which is using polyphenols could be a novel strategy for aging., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Acute lymphoblastic leukemia (ALL), one of the most common malignant human disorders, originates in different important genetic lesions in T-cell or B-cell progenitors. ALL is a malignant lymphoid progenitor with peak prevalence in children (2-5 years). The rate of survival when one is suffering from ALL depends on various agents including the age of the patient, responses to anti-leukemic therapy, and cell biology. miRNAs and epigenetics are important regulatory factors in the expression of genes. miRNAs are noncoding RNA with inhibitory effectors on specific mRNA. Patterns of DNA methylation are profoundly changed in ALL by epigenetic mechanisms. The deciphering of miRNA and the epigenetic pathogenesis in ALL could revolutionize response to the therapy and outcome, and create an enormous promise for novel approaches to reduce the toxic side-effects of intensive leukemia. Hence, pathogenetic miRNAs and epigenetics leading to the initiation and the progression of ALL are summarized in this review., (© 2018 Wiley Periodicals, Inc.)

Inflammatory bowel disease (IBD), as a chronic and recurrent inflammatory disorder, is caused by a dysregulated and aberrant immune response to exposed environmental factors in genetically susceptible individuals. Despite huge efforts in determining the molecular pathogenesis of IBD, an increasing worldwide incidence of IBD has been reported. MicroRNAs (miRNAs) are a set of noncoding RNA molecules that are about 22 nucleotides long, and these molecules are involved in the regulation of the gene expression. By clarifying the important role of miRNAs in a number of diseases, their role was also considered in IBD; numerous studies have been performed on this topic. In this review, we attempt to summarize a number of studies and discuss some of the recent developments in the roles of miRNAs in the pathophysiology, diagnosis, and treatment of IBD., (© 2018 Wiley Periodicals, Inc.)

Despite their simple structure, the Notch family of receptors regulates a wide-spectrum of key cellular processes including development, tissue patterning, cell-fate determination, proliferation, differentiation and, cell death. On the other hand, accumulating date pinpointed the role of non-coding microRNAs, namely miRNAs in cancer initiation/progression via regulating the expression of multiple oncogenes and tumor suppressor genes, as such the Notch signaling. It is now documented that these two partners are in one or in the opposite directions and rule together the cancer fate. Here, we review the current knowledge relevant to this tricky interplay between different miRNAs and components of Notch signaling pathway. Further, we discuss the implication of this crosstalk in cancer progression/regression in the context of cancer stem cells, tumor angiogenesis, metastasis and emergence of multi-drug resistance. Understanding the molecular cues and mechanisms that occur at the interface of miRNA and Notch signaling would open new avenues for development of novel and effective strategies for cancer therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The inability of cancer cells in taking care of DNA damages can lead to cancer development and/or progression. Due to the essential role of DNA repair in maintaining genomic stability, tightly controlled regulatory mechanism are required for these processes. Recent studies have shown a myriad of interactions among DNA damage response (DDR) components and miRNAs. While DDR modulates miRNA expression in transcriptional and post-transcriptional levels and affects miRNA degradation, miRNAs in turn, directly modulate the expression of multiple proteins in the DDR pathways, or indirectly fine-tune the expression of such proteins. A better understanding of DDR-miRNA interactions can facilitate the development of new anticancer agents targeting miRNAs involved in the DNA repair process. In this review, we provide a brief introduction about miRNA biogenesis and functions, DDR pathways, and recent findings about DDR-microRNA interactions. Finally, the therapeutic importance of miRNAs in modulation of DDR/DNA repair mechanisms will be discussed., (Copyright © 2016 Elsevier B.V. All rights reserved.)