Exosomes as novel tools for renal cell carcinoma therapy, diagnosis, and prognosis.

Background: Renal Cell Carcinoma (RCC) stands as a formidable challenge within the field of oncology, despite considerable research endeavors. The advanced stages of this malignancy present formidable barriers to effective treatment and management. Objective: This review aims to explore the potential of exosomes in addressing the diagnostic and therapeutic challenges associated with RCC. Specifically, it investigates the role of exosomes as biomarkers and therapeutic vehicles in the context of RCC management. Methods: For this review article, a comprehensive literature search was conducted using databases such as PubMed, employing relevant keywords to identify research articles pertinent to the objectives of the review. Initially, 200 articles were identified, which underwent screening to remove duplicates and assess relevance based on titles and abstracts, followed by a detailed examination of full texts. From the selected articles, relevant data were extracted and synthesized to address the review's objectives. The conclusions were drawn based on a thorough analysis of the findings. The quality was ensured through independent review and resolution of discrepancies among multiple reviewers. Results: Exosomes demonstrate potential as diagnostic tools for early detection, prognosis, and treatment monitoring in RCC. Their ability to deliver various therapeutic agents, such as small interfering RNAs, lncRNAs, chemotherapeutic drugs, and immune-stimulating agents, allows for a personalized approach to RCC management. By leveraging exosome-based technologies, precision and efficacy in treatment strategies can be significantly enhanced. Conclusion: Despite the promising advancements enabled by exosomes in the management of RCC, further research is necessary to refine exosome-based technologies and validate their efficacy, safety, and long-term benefits through rigorous clinical trials. Embracing exosomes as integral components of RCC diagnosis and treatment represents a significant step towards improving patient outcomes and addressing the persistent challenges posed by this malignancy in the field of oncology.

Current knowledge on therapeutic, diagnostic, and prognostics applications of exosomes in multiple myeloma: Opportunities and challenges.

Interactions between the plasma cells and the BM microenvironment of Multiple myeloma (MM) take place through factors such as exosomes. Many studies have confirmed the role of exosomes in these interactions. By carrying proteins, cytokines, lipids, microRNAs, etc. as their cargo, exosomes can regulate the interactions between MM plasma cells and neighboring cells and participate in the signaling between cancer cells and the environment. It has been shown that MM-derived exosomes can induce angiogenesis, enhance osteoblast activity, confer drug resistance, and have immunosuppressive properties. Abnormal cargos in endosomes originating from MM patients, can be used as a cancer biomarker to detect or screen early prognosis in MM patients. The native nanostructure of exosomes, in addition to their biocompatibility, stability, and safety, make them excellent candidates for therapeutic, drug delivery, and immunomodulatory applications against MM. On the other hand, exosomes derived from dendritic cells (DC) may be used as vaccines against MM. Thanks to the development of new 'omics' approaches, we anticipate to hear more about exosomes in fight against MM. In the present review, we described the most current knowledge on the role of exosomes in MM pathogenesis and their potential role as novel biomarkers and therapeutic tools in MM.

Distinctive Expression of Metastamirs in Breast Cancer Mesenchymal Stem Cells Isolated from Solid Tumor.

BACKGROUND: MSCs are a part of the tumor microenvironment, which secrete cytokines and chemokines. They can affect metastasis and the growth of tumors. metastamiRs are newly recognized regulatory elements of the metastasis pathway which are involved in epithelial-to-mesenchymal transition (EMT). OBJECTIVE: In the present study, we aimed to assess the expression profile of metastamiRs in the context of MSCs in correlation with their invasion and migration power. METHODS: tumor-isolated BC-MSCs and normal human mammary epithelial cells (HMECs) along with MCF-7, MDA-MB231, and MCF-10A cells were prepared and confirmed for their identity. The cells were assessed for CD44+CD24¯ percentage, Oct-4, and Survivin expression. GEO, KEGG, and TCGA databases were investigated to detect differential miR-expressions. Real-time PCR for 13 miRs was performed using LNA primers. Ultimately, Transwell-Matrigel assays as used to assess the level of migration and invasion. RESULTS: Our results indicated that some oncomiRs like miR-10b were upregulated in BC-MSCs, while the levels of miR-373 and miR-520c were similar to the MCF-10A. Generally, miR-200 family members were on lower levels compared to the other miR-suppressor (miR-146a, 146b, and 335). miR-31 and 193b were up-regulated in MCF-10A. The most invasiveness was observed in the MDA-MB231 cell line. CONCLUSION: We have demonstrated that the miR-expression levels of BC-MSCs are somewhat in between MCF-7 and MDA-MB231 miR-expression levels. This could be the logic behind the moderate level of invasion in BC-MSCs. Therefore, miR-therapy approaches such as miR-mimic or antagomiRs could be used for BC-MSCs in clinical cancer therapy.

Natural killer cell-derived exosomes for cancer immunotherapy: innovative therapeutics art.

Chimeric antigen receptor natural killer cells (CAR-NK) promote off-the-shelf cellular therapy for solid tumors and malignancy.However,, the development of CAR-NK is due to their immune surveillance uncertainty and cytotoxicity challenge was restricted. Natural killer cell-derived exosome (NK-Exo) combine crucial targeted cellular therapies of NK cell therapies with unique non-toxic Exo as a self-origin shuttle against cancer immunotherapy. This review study covers cytokines, adoptive (autologous and allogenic) NK immunotherapy, stimulatory and regulatory functions, and cell-free derivatives from NK cells. The future path of NK-Exo cytotoxicity and anti-tumor activity with considering non-caspase-independent/dependent apoptosis and Fas/FasL pathway in cancer immunotherapy. Finally, the significance and implication of NK-Exo therapeutics through combination therapy and the development of emerging approaches for the purification and delivery NK-Exo to severe immune and tumor cells and tissues were discussed in detail.

Immunomagnetic Isolation of HER2-Positive Breast Cancer Cells Using a Microfluidic Device.

Analysis of circulating tumor cells (CTCs) as a tool for monitoring metastatic cancers, early diagnosis, and evaluation of disease prognosis paves the way toward personalized cancer treatment. Developing an effective, feasible, and low-cost method to facilitate CTC isolation is, therefore, vital. In the present study, we integrated magnetic nanoparticles (MNPs) with microfluidics and used them for the isolation of HER2-positive breast cancer cells. Iron oxide MNPs were synthesized and functionalized with the anti-HER2 antibody. The chemical conjugation was verified by Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and dynamic light scattering/zeta potential analysis. The specificity of the functionalized NPs for the separation of HER2-positive from HER2-negative cells was demonstrated in an off-chip test setting. The off-chip isolation efficiency was 59.38%. The efficiency of SK-BR-3 cell isolation using a microfluidic chip with a S-shaped microchannel was considerably enhanced to 96% (a flow rate of 0.5 mL/h) without chip clogging. Besides, the analysis time for the on-chip cell separation was 50% faster. The clear advantages of the present microfluidic system offer a competitive solution in clinical applications.

Novel delivery of sorafenib by natural killer cell-derived exosomes-enhanced apoptosis in triple-negative breast cancer.

Aim: We investigated the delivery of sorafenib (SFB) to breast cancer spheroids by natural killer cell-derived exosomes (NK-Exos). Methods: SFB-NK-Exos were constructed by electroporation. Their antitumor effects were evaluated by methyl thiazolyl tetrazolium, acridine orange/ethidium bromide, 4',6-diamidino-2-phenylindole, annexin/propidium iodide, scratch and migration assay, colony formation, RT-PCR, western blot and lipophagy tests. Result: The loading efficacy was 46.66%. SFB-NK-Exos-treated spheroids showed higher cytotoxic effects (33%) and apoptotic population (44.9%). Despite the reduction of SFB concentration in the SFB-NK-Exos formulation, similar cytotoxic effects to those of free SFB were observed. Increased intracellular trafficking, sustained release of the drug and selective inhibitory effects demonstrated efficient navigation. Conclusion: This is the first report for SFB loading into NK-Exos, which led to significant cytotoxic intensification against cancer cells.

What is this summary about? This study describes the delivery of an anticancer drug called sorafenib (SFB) to laboratory-grown spherical masses of cancer cells called spheroids. Saucer-like cellular structures called exosomes were used as drug-delivery tools. These exosomes were produced by a subgroup of immune cells called natural killer (NK) cells. NK cells are responsible for killing cancer cells. So, these exosomes share similar anticancer properties with NK cells. We wanted to test whether exosomes loaded with SFB would have better anticancer effects. What were the results? Using different methods, SFB was loaded within the exosomes and delivered to the spheroids. The obtained results showed that a combination of exosomes and SFB could improve the targeting efficacy, reducing the side effects to the normal cells and allowing continuous release of the drug. The spheroids were killed with higher efficacy following this treatment. What do the results of the study mean? The combination of NK cell-derived exosomes and SFB could lead to better cytotoxicity against cancer cells. Therefore, this strategy could have better anticancer effects compared with SFB treatment alone.

Impact of SNPs, off-targets, and passive permeability on efficacy of BCL6 degrading drugs assigned by virtual screening and 3D-QSAR approach.

B-cell lymphoma 6 (BCL6) regulates various genes and is reported to be overexpressed in lymphomas and other malignancies. Thus, BCL6 inhibition or its tagging for degradation would be an amenable therapeutic approach. A library of 2500 approved drugs was employed to find BCL6 inhibitory molecules via virtual screening. Moreover, the 3D core structure of 170 BCL6 inhibitors was used to build a 3D QSAR model and predict the biological activity. The SNP database was analyzed to study the impact on the destabilization of BCL6/drug interactions. Structural similarity search and molecular docking analyses were used to assess the interaction between possible off-targets and BCL6 inhibitors. The tendency of drugs for passive membrane permeability was also analyzed. Lifitegrast (DB11611) had favorable binding properties and biological activity compared to the BI-3802. Missense SNPs were located at the essential interaction sites of the BCL6. Structural similarity search resulted in five BTB-domain containing off-target proteins. BI-3802 and Lifitegrast had similar chemical behavior and binding properties against off-target candidates. More interestingly, the binding affinity of BI-3802 (against off-targets) was higher than Lifitegrast. Energetically, Lifitegrast was less favorable for passive membrane permeability. The interaction between BCL6 and BI-3802 is more prone to SNP-derived variations. On the other hand, higher nonspecific binding of BI-3802 to off-target proteins could bring about higher undesirable properties. It should also be noted that energetically less desirable passive membrane translocation of Lifitegrast would demand drug delivery vehicles. However, further empirical evaluation of Lifitegrast would unveil its true potential.

Bioactivity of Exosomes Derived from Trained Natural Killer Cells versus Non-Trained One: More Functional and Antitumor Activity.

Background: Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system, capable of killing viral-infected and cancerous cells. NK cell-mediated immunotherapy has remarkably changed the current paradigm of cancer treatment in recent years. It emerged as a safe and effective therapeutic approach for patients with advanced-stage leukemia. Several immune-escape mechanisms can be enacted by cancer cells to avoid NK-mediated killing. Exosomes released by NK cells that carry proteins and miRNAs can exert an antitumor effect. In the present study, we hypothesized that maybe exosomes derived from trained natural killer cells show more antitumor effect in comparison to non-trained one. Methods: PBMC was separated by the Ficoll method and cultured with IL-2 for 21 days to expand NK cells. The NK cells were co-cultured with K562 for 72 hours and exosome-derived co-cultured (as trained) and natural killer cell-derived exosomes (as non-trained) were extracted by Exo kit. The exosomes were confirmed by dynamic light scattering (DLS), transmission electron microscopy (TEM), flow cytometry, and western blotting. The K562 cells were separately treated by trained and non-trained exosomes and MTT assay, apoptosis, and real-time PCR were performed. Results: Based on flow cytometry, CD56 marker was 89.7% and 40.1% for NK cells and NK-derived exosomes, respectively. CD63 and CD9 were positive for exosomes by western blotting. The morphology of exosome was confirmed by TEM. Treated K562 cells by trained exosomes indicated the diminished cell viability and higher apoptosis. Furthermore, the trained exosomes showed up-regulation in both P53 and caspase3 genes as compared with non-trained sample. Discussion. Trained Exos showed a potent inhibitory effect on proliferation and induced apoptosis on K562 cell lines compared to the same dose of non-trained Exos. According to the results of qRT-PCR, trained Exos exerted an antitumor activity through up-regulation of caspase 3 and P53 in the apoptotic signaling pathway in tumor cells. Our findings indicate an effective action of trained Exos against cancer cells.

Liothyronine could block the programmed death-ligand 1 (PDL1) activity: an e-Pharmacophore modeling and virtual screening study.

PURPOSE: The interaction between PD-L1 on tumor cells and the programmed death 1 (PD1) on immune cells helps them to escape the immune system elimination. Therefore, developing therapeutic agents to block this interaction has garnered a lot of attention as a therapeutic approach. In the present study, we have tried to screen for an inhibitory compound to inhibit the interaction between the PD1/PD-L1 molecules. METHODS: In this regard, the structure of PD-L1 and its inhibitor were prepared and employed to generate an e-Pharmacophore model. A library of approved compounds was prepared and toxicity analysis using Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) predictor was performed. The built e-Pharmacophore model was validated and used to screen the prepared compound library. Ligand docking and binding energy calculation were performed on the screened ligands. RESULTS: A seven-feature e-Pharmacophore model was generated using the PD-L1 complex. All of the compounds within the library passed the ADMET criteria. Performing the virtual screening, only 79 compounds have survived the criteria to fit four pharmacophoric features. The compound with the highest binding energy was the liothyronine (T3). CONCLUSION: The ability of T3 in PD1/PD-L1 checkpoint blockade along with its potential in T4 reduction could be a desirable combination in cancer treatment. These abilities of T3 could be used to restore the ability of the immune system to eliminate tumor cells.

SARS-CoV-2 Proteome Harbors Peptides Which Are Able to Trigger Autoimmunity Responses: Implications for Infection, Vaccination, and Population Coverage.

Autoimmune diseases (ADs) could occur due to infectious diseases and vaccination programs. Since millions of people are expected to be infected with SARS-CoV-2 and vaccinated against it, autoimmune consequences seem inevitable. Therefore, we have investigated the whole proteome of the SARS-CoV-2 for its ability to trigger ADs. In this regard, the entire proteome of the SARS-CoV-2 was chopped into more than 48000 peptides. The produced peptides were searched against the entire human proteome to find shared peptides with similar experimentally confirmed T-cell and B-cell epitopes. The obtained peptides were checked for their ability to bind to HLA molecules. The possible population coverage was calculated for the most potent peptides. The obtained results indicated that the SARS-CoV-2 and human proteomes share 23 peptides originated from ORF1ab polyprotein, nonstructural protein NS7a, Surface glycoprotein, and Envelope protein of SARS-CoV-2. Among these peptides, 21 peptides had experimentally confirmed equivalent epitopes. Amongst, only nine peptides were predicted to bind to HLAs with known global allele frequency data, and three peptides were able to bind to experimentally confirmed HLAs of equivalent epitopes. Given the HLAs which have already been reported to be associated with ADs, the ESGLKTIL, RYPANSIV, NVAITRAK, and RRARSVAS were determined to be the most harmful peptides of the SARS-CoV-2 proteome. It would be expected that the COVID-19 pandemic and the vaccination against this pathogen could significantly increase the ADs incidences, especially in populations harboring HLA-B*08:01, HLA-A*024:02, HLA-A*11:01 and HLA-B*27:05. The Southeast Asia, East Asia, and Oceania are at higher risk of AD development.

Metastasis Inhibition by Cell Type Specific Expression of BRMS1 Gene under The Regulation of miR200 Family Response Elements.

OBJECTIVE: Specific expression of therapeutic genes in cancer therapy has been per used for many years. One of the innovative strategies that have recently been introduced is employing miRNA response elements (MREs) of microRNAs (whose expression are reduced or inhibited in cancerous cells) into the 3´UTR of the therapeutic genes for their specific expression. Accordingly, MREs of anti-metastatic miRNA family have been used in 3´UTR of the metastasis suppressor gene in the corresponding cells to evaluate the level of metastatic behavior. MATERIALS AND METHODS: In this experimental study, 3´UTR of the ZEB1 gene with 592 bp length, encompassing multiple MREs of miR-141, miR-429, miR-200b and miR-200c, was employed to replace BRMS1 3´UTR. The obtained vector was then assessed in the context of MCF-10A, MDA-MB231 and MCF-7 cells. RESULTS: It was shown that the employed MREs are able to up-regulate BRMS expression in the metastatic MDAMB231 cells (almost 3.5-fold increase), while it was significantly reduced within tumorigenic/non-metastatic MCF-7 cells. Specific expression of BRMS1 in metastatic cells led to a significant reduction in their migratory and invasive characteristics (about 65% and 55%, respectively). Two-tailed student's t test was utilized for statistical analysis. CONCLUSION: It was demonstrated that a chimeric vector containing BRMS1 which is regulated by miR-200 family response element may represent a promising therapeutic tool. This is due to the capability of the chimeric vector for cell type-specific expression of anti-metastatic genes with lowest side-effects. It consequently prohibits the invasive characteristics of metastatic cells.

In silico Approaches for the Design and Optimization of Interfering Peptides Against Protein-Protein Interactions.

Large contact surfaces of protein-protein interactions (PPIs) remain to be an ongoing issue in the discovery and design of small molecule modulators. Peptides are intrinsically capable of exploring larger surfaces, stable, and bioavailable, and therefore bear a high therapeutic value in the treatment of various diseases, including cancer, infectious diseases, and neurodegenerative diseases. Given these promising properties, a long way has been covered in the field of targeting PPIs via peptide design strategies. In silico tools have recently become an inevitable approach for the design and optimization of these interfering peptides. Various algorithms have been developed to scrutinize the PPI interfaces. Moreover, different databases and software tools have been created to predict the peptide structures and their interactions with target protein complexes. High-throughput screening of large peptide libraries against PPIs; "hotspot" identification; structure-based and off-structure approaches of peptide design; 3D peptide modeling; peptide optimization strategies like cyclization; and peptide binding energy evaluation are among the capabilities of in silico tools. In the present study, the most recent advances in the field of in silico approaches for the design of interfering peptides against PPIs will be reviewed. The future perspective of the field and its advantages and limitations will also be pinpointed.

Evaluation of Differentiation Quality of Several Differentiation Inducers of Bone Marrow-derived Mesenchymal Stem Cells to Nerve Cells by Assessing Expression of Beta-tubulin 3 Marker: A Systematic Review.

Neurological diseases have different etiological causes. Contemporary, developing an effective treatment for these diseases is an ongoing challenge. Cell therapy is recognized as one of the promising solutions for the treatment of these diseases. Amongst various types of stem cells, bone marrow-derived mesenchymal stem cells (BM-MSC) are known to be the most widely used stem cells. These cells are endowed with appealing properties such as the ability to differentiate into other cell types, including the muscle, liver, glial, and nerve cells. In this review study, we have systematically evaluated the ability of a variety of chemical compounds used in the last ten years to differentiate BM-MSCs into neurons by examining the expression level of beta-tubulin 3 protein. The present study is a systematic search performed at three separate databases, including PubMed, ScienceDirect, and Embase from August 2009 to August 2019. The search results in the three mentioned databases were 323 articles and finally, 8 articles were selected and carefully examined considering the inclusion and exclusion criteria. The results showed that different chemical compounds such as ROCK inhibitors, sex steroid hormones, bFGF, NGF, Noggin, 4 OHT, TSA, VPA, Antidepressants, Neurosteroids (Dex and E2), and DHA are involved in different signaling pathways, such as ERK, AKT, BMP, DHA / GPR40, Rho-dependent phosphorylation, and histone deacetylase inhibitors. Further investigation of these signaling pathways may open the way for better differentiation of BM-MSCs into neurons.

microRNA-181 serves as a dual-role regulator in the development of human cancers.

MicroRNAs (miRNAs) as the regulatory short noncoding RNAs are involved in a wide array of cellular and molecular processes. They negatively regulate gene expression and their dysfunction is correlated with cancer development through modulation of multiple signaling pathways. Therefore, these molecules could be considered as novel biomarkers and therapeutic targets for more effective management of human cancers. Recent studies have demonstrated that the miR-181 family is dysregulated in various tumor tissues and plays a pivotal role in carcinogenesis. They have been shown to act as oncomirs or tumor suppressors considering their mRNA targets and to be involved in cell proliferation, apoptosis, autophagy, angiogenesis and drug resistance. Additionally, these miRNAs have been demonstrated to exert their regulatory effects through modulating multiple signaling pathways including PI3K/AKT, MAPK, TGF-b, Wnt, NF-κB, Notch pathways. Given that, in this review, we briefly summarise the recent studies that have focused on the roles of miRNA-181 family as the multifunctional miRNAs in tumorigenesis and cancer development. These miRNAs may serve as diagnostic and prognostic biomarkers or therapeutic targets in human cancer gene therapy.

Serum DKK1 is correlated with γ peak of serum electrophoresis in multiple myeloma: a multicenter biomarker study.

Aim: DKK1 is reported to be produced at high levels by myeloma cells. Therefore, the applicability of DKK1 as a tumor marker for multiple myeloma (MM) diagnosis was examined. Methods: Serum samples were collected and analyzed by DKK1 concentration kit and capillary zone electrophoresis. Then, the obtained results were statically analyzed. Results: It has been determined that the 10 ng/ml of DKK1 is the optimal level for MM diagnosis. Moreover, there was an ascending linear correlation between the DKK1 concentration and γ peak. Discussion: The observed correlation could be rooted in the positive feedback loop between MM cells and the mesenchymal stem cells. In view of these results, DKK1 could be deemed as diagnostic marker for MM.

Additive effect of metastamiR-193b and breast cancer metastasis suppressor 1 as an anti-metastatic strategy.

BACKGROUND: It has been reported that enhancing the cellular levels of miR-193b as well as breast cancer-metastasis-suppressor-1 (BRMS1) protein is associated with diminished metastatic characteristics in breast cancer. In view of these facts, as a new therapeutic intervention, we employed a restoration-based strategy using both miR-193b-3p mimic and optimized BRMS1 in the context of a chimeric construct. METHODS: miR-193b-3p and BRMS1 genes were cloned and the resulting plasmids were transfected into the MDA-MB231, MCF-7 and MCF-10A cell lines. microRNA expression levels were assessed by rea time PCR using LNA-primer and protein expression was confirmed by western blot method. Then, apoptosis, MTT, colony formation and invasion assays were carried out. RESULTS: The expression levels of miR-146a, miR-146b and miR-373 were up-regulated, while the miR-520c, miR-335 and miR-10b were down-regulated following the exogenous BRMS1 expression. The exogenous over-expression of BRMS1 was associated with higher amounts of endogenous miR-193b-3p expression and enabled more efficient targeting of the 3'UTR of uPA. Although, miR-193b-3p and BRMS1 are individually capable of suppressing breast cancer cell growth, migration and invasion abilities, their cistronic expression was capable of enhancing the ability to repress the breast cancer cells invasion. CONCLUSIONS: Our results collectively indicated the existence of an additive anti-metastatic effect between miR-193b-3p and BRMS1. Moreover, it has been hypothesized that the exogenous expression of a protein can effect endogenous expression of non-relevant microRNA. Our findings provide new grounds for miR-restoration therapy applications as an amenable anti-metastatic strategy.

Inhibition of breast cancer metastasis by co-transfection of miR-31/193b-mimics.

OBJECTIVES: Various studies have been conducted to reduce the metastatic behavior of cancerous cells. In this regard, ectopic expression of anti-metastatic microRNAs by miR-mimic and miR-restoration-based therapies could bring new insights to the field. In the present study, the consequences of co-transfecting breast cancer cell lines with miR-193b and miR-31 were investigated via invasion and migration assays. MATERIALS AND METHODS: Double stranded oligonucleotide of mature miR-193b-3p and miR-31-5p were cloned into pcDNA 6.2gw/EmGFP plasmid. The resulting plasmids were used for transfection. Real time-PCR was performed to assess the expression of miR-193b and miR-31 as well as Ras homolog gene family member A (RhoA) and urokinase-type plasminogen activator (uPA) as miR targets. Scratch, Transwell migration and Matrigel invasion assays were carried out to assess the extent of migration and invasion of cell lines. RESULTS: The most significant increase in expression of miRs belonged to the single transfection of mimic-miRs in MDA-MB231. Although the co-transfection was not as successful as single transfection in miR expression, it was significantly more effective in inhibition of the cells invasive potential. CONCLUSION: Although the miR-restoration therapy based on co-transfection of two miRs could be less effective in expression of each miRNA, the resulting decrease in metastatic behavior of the cells is more significant due to collective effect of co-transfection to decrease target gene expression. Our results revealed that employing this sort of combinatorial strategies could lead to more efficient reduction in metastatic behavior. It seems that using this strategy would bring about more successful therapeutic outcomes.

Lung cancer and miRNAs: a possible remedy for anti-metastatic, therapeutic and diagnostic applications.

INTRODUCTION: Lung cancer still accounts for the leading cause of cancer-related deaths worldwide and despite the emerging advances in diagnostic and therapeutic techniques it remains to be a serious global public health concern. Micro-ribonucleic acids (microRNAs) are responsible for invasion and metastasis of various tumors including lung cancer which underscores the necessity of understanding their functions. Areas covered: Herein, we aim to summarize the recent advances made in our understanding of the miRNAs with special reference to lung cancer. Moreover, the role of miRNAs in crucial cellular processes will be elucidated. Various applications of the miRNAs would be explained and different kinds of them would be discussed to delineate their significance in lung cancer biology, therapy and diagnosis. Expert commentary: the miRNA study in the field of respiratory disease and specially lung cancer has emerged lately. Given the several miRNAs, which are in the clinical trials, this field is passing through its maturation phase which ultimately could rise to a robust tool for lung cancer therapy, diagnosis and prevention.

Knockdown of microRNA-29a Changes the Expression of Heat Shock Proteins in Breast Carcinoma MCF-7 Cells.

Breast cancer is the most commonly occurring cancer among women. MicroRNAs as noncoding small RNA molecules play pivotal roles in cancer-related biological processes. Increased levels of microRNA-29a in the serum of breast cancer patients have been reported. Since heat shock proteins (HSPs) play important roles in cell events, the quantitative fluctuations in their cellular levels could be deemed as key indicators of how the exerted treatment alters cell behavior. In this regard, using an antisense small RNA, we attempted to investigate the effects of miR-29a knockdown on the expression of HSPs genes in the MCF-7 breast cancer cell line. MCF-7 cells were cultured in high-glucose Dulbecco's modified Eagle's medium with 10% FBS. Studied cells were subdivided into five groups: treated with scramble, anti-miR-29a, anti-miR-29a + Taxol, Taxol, and control. Taxol was added 24 h post-anti-miR transfection and RNA extraction, and cDNA synthesis was done 48 h later. The changes in expression of HSP27, HSP40, HSP60, HSP70, and HSP90 were evaluated by real-time PCR. Our results revealed that inhibitors of microRNA-29a promote apoptosis through upregulation of HSP60 level and downregulation of HSP27, HSP40, HSP70, and HSP90 levels and could be contemplated as a compelling alternative for Taxol employment with similar effects and/or to sensitize cancer cells to chemotherapy with fewer side effects.