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Long noncoding RNAs (lncRNAs) are a diverse class of RNAs whose functions are widespread in all branches of life and have been the focus of attention in the last decade. While a huge number of lncRNAs have been identified, there is still much work to be done and plenty to be learned. In the current review, we begin with the biogenesis and function of lncRNAs as they are involved in the different cellular processes from regulating the architecture of chromosomes to controlling translation and post‐translation modifications. Questions on how overexpression, mutations, or deficiency of lncRNAs can affect the cellular status and result in the pathogenesis of various human diseases are responded to. Besides, we allocate an overview of several studies, concerning the application of lncRNAs either as diagnostic and prognostic biomarkers or novel therapeutics. We also introduce the currently available techniques to explore details of lncRNAs such as their function, cellular localization, and structure. In the last section, as exponentially growing data in this area need to be gathered and organized in comprehensive databases, we have a particular focus on presenting general and specialized databases. Taken together, with this review, we aim to provide the latest information on different aspects of lncRNAs to highlight their importance in physiopathologic states and take a step towards helping future studies. Significance statement: This study aims to review the roles of long noncoding RNAs in the pathogenesis of diseases and introduce them as potential candidates for diagnostic biomarkers and therapeutic targets. However, there are a significant number of lncRNAs whose molecular mechanisms and functions are poorly understood; illustrating the importance of bioinformatics tools and databases to predict and analyze the structure, function, and other features of these molecules. In addition, developing high‐throughput techniques has accelerated the process of lncRNA research. Thus, we reviewed the bioinformatic tools and different techniques to explore diverse aspects of lncRNAs, hoping this information will be a beacon of light for future studies. [ABSTRACT FROM AUTHOR]

Despite remarkable advances in different types of cancer therapies, an effective therapeutic strategy is still a major and significant challenge. One of the most promising approaches in this regard is immunotherapy, which takes advantage of the patients' immune system; however, the many mechanisms that cancerous cells harbor to extend their survival make it impossible to gain perfect eradication of tumors. The response rate to cancer immunotherapies, especially checkpoint inhibitors and adoptive T cell therapy, substantially differs in various cancer types with the highest rates in advanced melanoma and non‐small cell lung cancer. Indeed, the lack of response in many tumors indicates primary resistance that can originate from either tumor cells (intrinsic) or tumor microenvironment (extrinsic). On the other hand, some tumors show an initial response to immunotherapy followed by relapse in few months (acquired resistance). Understanding the underlying molecular mechanisms of immunotherapy resistance makes it possible to develop effective strategies to overcome this hurdle and boost therapy outcomes. In this review, we take a look at immunotherapy strategies and go through a number of primary and acquired resistance mechanisms. Also, we present various ongoing methods to overcoming resistance and introduce some promising fields to improve the outcome of immunotherapy in patients affected with cancer. [ABSTRACT FROM AUTHOR]

Background: In the new era of tailored cancer treatment strategies, finding a molecule to regulate a wide range of intracellular functions is valuable. The unique property of nuclear receptor peroxisome proliferator‐activated receptor‐γ (PPARγ; PPARG) in transmitting the anti‐survival signals of the chemotherapeutic drugs has fired the enthusiasm into the application of this receptor in cancer treatment. Objectives: We aimed to investigate the expression of PPARγ and one of its downstream targets PTEN in non‐M3 acute myeloid leukemia (AML) patients. We also investigated the therapeutic value of PPARγ stimulation using pioglitazone in the AML‐derived U937 cell line. Methods: The blood samples from 30 patients diagnosed with non‐M3 AML as well as 10 healthy individuals were collected and the mRNA expression levels of PPARγ and PTEN were evaluated. Additionally, we used trypan blue assay, MTT assay, and flow cytometry analysis to evaluate the anti‐leukemic effects of pioglitazone on U937 cells. Results: While PTEN was significantly downregulated in AML patients as compared to the control group, the expression of PPARγ was increased in the patients' group. The expression level of PPARγ was also negatively correlated with PTEN; however, it was not statistically significant. Besides, PPARγ stimulation using pioglitazone reduced survival and proliferative capacity of U937 cells through inducing apoptosis and suppression of cell transition from the G1 phase of the cell cycle. Conclusion: The results of the present study shed more light on the importance of PPARγ and its stimulation in the therapeutic strategies of AML. [ABSTRACT FROM AUTHOR]

The toll‐like receptor (TLR) family consists of vital receptors responsible for pattern recognition in innate immunity, making them the core proteins involved in pathogen detection and eliciting immune responses. The most studied member of this family, TLR4, has been the center of attention regarding its contributory role in many inflammatory diseases including sepsis shock and asthma. Notably, mounting pieces of evidence have proved that this receptor is aberrantly expressed on the tumor cells and the tumor microenvironment in a wide range of cancer types and it is highly associated with the initiation of tumorigenesis as well as tumor progression and drug resistance. Cancer therapy using TLR4 inhibitors has recently drawn scientists' attention, and the promising results of such studies may pave the way for more investigation in the foreseeable future. This review will introduce the key proteins of the TLR4 pathway and how they interact with major growth factors in the tumor microenvironment. Moreover, we will discuss the many aspects of tumor progression affected by the activation of this receptor and provide an overview of the recent therapeutic approaches using various TLR4 antagonists. [ABSTRACT FROM AUTHOR]

Although the identification of tyrosine kinase inhibitors (TKIs) has changed the treatment paradigm of many cancer types including chronic myeloid leukemia (CML), still adjustment of neoplastic cells to cytotoxic effects of anticancer drugs is a serious challenge. In the area of drug resistance, epigenetic alterations are at the center of attention and the present study aimed to evaluate whether blockage of epigenetics mechanisms using a pan‐histone deacetylase (HDAC) inhibitor induces cell death in CML‐derived K562 cells. We found that the abrogation of HDACs using panobinostat resulted in a reduction in survival of the K562 cell line through p27‐mediated cell cycle arrest. Noteworthy, the results of the synergistic experiments revealed that HDAC suppression could be recruited as a way to potentiate cytotoxicity of Imatinib and to enhance the therapeutic efficacy of CML. Here, we proposed for the first time that the inhibitory effect of panobinostat was overshadowed, at least partially, through the aberrant activation of the phosphoinositide 3‐kinase (PI3K)/c‐Myc axis. Meanwhile, we found that upon blockage of autophagy and the proteasome pathway, as the main axis involved in the activation of autophagy, the anti‐leukemic property of the HDAC inhibitor was potentiated. Taken together, our study suggests the beneficial application of HDAC inhibition in the treatment strategies of CML; however, further in vivo studies are needed to determine the efficacy of this inhibitor, either as a single agent or in combination with small molecule inhibitors of PI3K and/or c‐Myc in this malignancy. [ABSTRACT FROM AUTHOR]

In the dark path of tumorigenesis, the more carefully the cancer biology is studied, the more brilliant answers could be given to the countless questions about its orchestrating derivers. The identification of the correlation between Toll‐like receptors (TLRs) and different processes involved in carcinogenesis was one of the single points of blinding light highlighting the interconnection between the immune system and cancer. TLRs are a wide family of single‐pass membrane‐spanning receptors that have developed through the evolution to recognize the structurally conserved molecules derived from microorganisms or damaged cells. But this is not everything about these receptors as they could orchestrate several downstream signalling pathways leading to the formation or suppression of cancer cells. The present review is tempted to provide a concise schematic about the biology and the characters of TLRs and also summarize the major findings of the regulatory role of TLRs and their associated signalling in the pathogenesis of human cancers. [ABSTRACT FROM AUTHOR]

At the forefront of the battle against pathogens or any endogenously released molecules, toll‐like receptors (TLRs) play an important role as the most noble pattern recognition receptors. The ability of these receptors in distinguishing "self" and "non‐self" antigens is a cornerstone in the innate immunity system; however, misregulation links inflammatory responses to the development of human cancers. It has been known for some time that aberrant expression and regulation of TLRs not only endows cancer cells an opportunity to escape from the immune system but also supports them through enhancing proliferation and angiogenesis. Over the past decades, cancer research studies have witnessed a number of preclinical and clinical breakthroughs in the field of TLR modulators and some of the agents have exceptionally performed well in advanced clinical trials. In the present review, we have provided a comprehensive review of different TLR agonists and antagonists and discuss their limitations, toxicities, and challenges to outline their future incorporation in cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Aim Survivin, an inhibitor of apoptosis protein, is overexpressed in most cancers and is associated with chemotherapy resistance, increased tumor recurrence and shorter patient survival. Several survivin splice variants have been described, and none of their expressions have been defined in acute promyelocytic leukemia (APL). Methods Expression of the survivin gene isoforms (survivin, -2α, -2B, -ΔΕx3 and -3B) were analyzed in 50 peripheral blood and 19 bone marrow samples that were collected at different phases of the disease (diagnostic, remission and relapse) in APL patients treated with arsenic trioxide (ATO) as a front-line therapy. In addition, the human APL-derived cell line (NB4) was analyzed for the expression of survivin isoforms and capsase-3 in response to the ATO. Results Survivin and its variants were overexpressed significantly in patient's bone marrow samples compared to peripheral blood or normal samples. Their expression was decreased after ATO treatment in both NB4 cells (except survivin-2α) and APL patients along with PML-RARα copy number reduction. Downregulation of survivin isoforms was associated with an increase in both caspase-3 gene expression and its enzymatic activity levels. In a patient who did not respond to ATO treatment, expression of survivin isoforms (except survivin-2α) were highly increased during the induction therapy. Conclusion Survivin isoforms are upregulated in APL patients, and their expression is diminished during the ATO treatment. In addition, overexpression of survivin and its variants (except survivin-2α) are associated with unfavorable results, suggesting that they may play an important role in mechanisms underlying the resistance of APL cells to ATO. [ABSTRACT FROM AUTHOR]

Aim In recent years, a few cases of chronic myeloid leukemia (CML) have been reported with both BCR-ABL and JAK2V617F mutations. Moreover, mutations in the additional sex comb-like 1 ( ASXL1) gene were recently shown in various myeloid malignancies.There were no previous studies investigating the incidence of the ASXL1 and JAK2V617F mutations in Iranian patients with CML. Consequently, this study focuses on the analysis of these mutations in patients with CML. Methods In total, 66 patients with a clinical diagnosis of CML were examined at the time of diagnosis. Thirty healthy subjects were checked as controls. Exon 12 of ASXL1 was amplified from genomic DNA and bidirectionally sequenced. We also performed JAK2V617F screening by amplification refractory mutation system-polymerase chain reaction and sequencing. Results Mutations in the ASXL1 gene were found in five out of 66 CML patients (7.6%). We identified a novel variant (c.1968G > A, p.Asp656Asn) in one of the patients that has not been reported before. We also identified BCR-ABL and JAK2V617F mutations simultaneously in four patients (6%). Conclusion Our demonstration of ASXL1 mutation, a putative tumor suppressor gene, represents an important molecular abnormality in CML. We also showed that concomitant detection of BCR-ABL and JAK2V617F mutations has a relatively high incidence in Iranian patients. [ABSTRACT FROM AUTHOR]