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Purpose of the study. Determination of the expression of microRNA‑34, microRNA‑130, microRNA‑148, microRNA‑181, microRNA‑194 and microRNA‑605 in colon tumor tissue depending on the clinical and morphological features of the tumor and the effectiveness of treatment.Materials and methods. The study included 56 patients diagnosed with colorectal cancer aged 43 to 75 years with the average age of 54 years. Taking into account the local prevalence of the process patients received surgical or combined treatment, including neoadjuvant chemotherapy, in the clinics of the Cancer Research Institute, Tomsk NRMC. MicroRNA expression was determined by polymerase chain reaction (PCR) in real time.Results. The obtained information revealed the relation of microRNA‑130 to the tumor size. The development of regional metastases was associated with changes in microRNA‑130, microRNA‑194 and microRNA‑605. The level of histological organization of the tumor was associated with microRNA‑34, microRNA‑130, microRNA‑148, and the response to therapy – with microRNA‑130, microRNA‑148 and microRNA‑605. In addition, according to the study, the significance of microRNA‑130 was revealed, which is associated with tumor spread, histological differentiation and response to antitumor therapy.Conclusion. The features of expression of microRNA‑34, microRNA‑130, microRNA‑148, microRNA‑181, microRNA‑194 and microRNA‑605 associated with clinical and morphological features of colon tumors were revealed. Correlations between the studied indicators are noted, which probably determine the outcome and prognosis of the disease.

Abstract Objectives In 2012, Liu et al. reported that miR-34 is an age-related miRNA regulating age-associated events and long-term brain integrity in Drosophila. They demonstrated that modulating miR-34 and its downstream target, Eip74EF, showed beneficial effects on an age-related disease using a Drosophila model of Spinocerebellar ataxia type 3 expressing SCA3trQ78. These results imply that miR-34 could be a general genetic modifier and therapeutic candidate for age-related diseases. Thus, the goal of this study was to examine the effect of miR-34 and Eip47EF on another age-related Drosophila disease model. Results Using a Drosophila eye model expressing mutant Drosophila VCP (dVCP) that causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), or multisystem proteinopathy (MSP), we demonstrated that abnormal eye phenotypes generated by dVCPR152H were rescued by Eip74EF siRNA expression. Contrary to our expectations, miR-34 overexpression alone in the eyes with GMR-GAL4 resulted in complete lethality due to the leaky expression of GMR-GAL4 in other tissues. Interestingly, when miR-34 was co-expressed with dVCPR152H, a few survivors were produced; however, their eye degeneration was greatly exacerbated. Our data indicate that, while confirming that the downregulation of Eip74EF is beneficial to the dVCPR152H Drosophila eye model, the high expression level of miR-34 is actually toxic to the developing flies and the role of miR-34 in dVCPR152H-mediated pathogenesis is inconclusive in the GMR-GAL4 eye model. Identifying the transcriptional targets of Eip74EF might provide valuable insights into diseases caused by mutations in VCP such as ALS, FTD, and MSP.

Objectives: In 2012, Liu et al. reported that miR-34 is an age-related miRNA regulating age-associated events and long-term brain integrity in Drosophila. They demonstrated that modulating miR-34 and its downstream target, Eip74EF, showed beneficial effects on an age-related disease using a Drosophila model of Spinocerebellar ataxia type 3 expressing SCA3trQ78. These results imply that miR-34 could be a general genetic modifier and therapeutic candidate for age-related diseases. Thus, the goal of this study was to examine the effect of miR-34 and Eip47EF on another age-related Drosophila disease model. Results: Using a Drosophila eye model expressing mutant Drosophila VCP (dVCP) that causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), or multisystem proteinopathy (MSP), we demonstrated that abnormal eye phenotypes generated by dVCPR152H were rescued by Eip74EF siRNA expression. Contrary to our expectations, miR-34 overexpression alone in the eyes with GMR-GAL4 resulted in complete lethality due to the leaky expression of GMR-GAL4 in other tissues. Interestingly, when miR-34 was co-expressed with dVCPR152H, a few survivors were produced; however, their eye degeneration was greatly exacerbated. Our data indicate that, while confirming that the downregulation of Eip74EF is beneficial to the dVCPR152HDrosophila eye model, the high expression level of miR-34 is actually toxic to the developing flies and the role of miR-34 in dVCPR152H-mediated pathogenesis is inconclusive in the GMR-GAL4 eye model. Identifying the transcriptional targets of Eip74EF might provide valuable insights into diseases caused by mutations in VCP such as ALS, FTD, and MSP. [ABSTRACT FROM AUTHOR]

Abstract Background It remains essential for non-alcoholic fatty liver (NAFLD) patients, to develop a sensitive and specific diagnostic model. Data regarding the use of micro (mi)RNA-34 for NAFLD diagnosis are few. Routine clinical assessment, laboratory tests were done for Egyptian individuals (n = 314) were included (100 healthy individuals and 214 NAFLD patients). Quantification of miRNA-34 was done using real-time PCR. Extremely significant variables were entered into stepwise logistic regression. The diagnostic power of variables was estimated by the area under the ROC (AUC). Results MiRNA-34 levels were higher in NAFLD patients than healthy individuals with a significant difference (P< 0.0001). The multivariate analysis was used to evaluate the NAFLD-associated variables (CRP, cholesterol, body mass index (BMI), ALT had p< 0.0001 while mRNA-34 had (p=0.0004). The AUCs (CI) of candidate NAFLD markers were in the order of miRNA-34 0.72 (0.66–0.77) < ALT 0.73 (0.67–0.79) < BMI 0.81 (0.76–0.86) < cholesterol < 0.85 (0.79–0.90) < CRP 0.88 (0.84–0.92). We developed a novel index for discriminating patients with NAFLD named NAFLD Mark. AUC was jumped to 0.98 (0.93–0.99) when five markers were combined. The AUC of NAFLD mark for NAFLD detection was higher than the AUCs of seven common NAFLD indexes (0.44–0.86). Conclusions The NAFLD mark is a non-invasive and highly sensitive and specific model for NAFLD diagnosis.

Background: It remains essential for non-alcoholic fatty liver (NAFLD) patients, to develop a sensitive and specific diagnostic model. Data regarding the use of micro (mi)RNA-34 for NAFLD diagnosis are few. Routine clinical assessment, laboratory tests were done for Egyptian individuals (n = 314) were included (100 healthy individuals and 214 NAFLD patients). Quantification of miRNA-34 was done using real-time PCR. Extremely significant variables were entered into stepwise logistic regression. The diagnostic power of variables was estimated by the area under the ROC (AUC). Results: MiRNA-34 levels were higher in NAFLD patients than healthy individuals with a significant difference (P< 0.0001). The multivariate analysis was used to evaluate the NAFLD-associated variables (CRP, cholesterol, body mass index (BMI), ALT had p< 0.0001 while mRNA-34 had (p=0.0004). The AUCs (CI) of candidate NAFLD markers were in the order of miRNA-34 0.72 (0.66–0.77) < ALT 0.73 (0.67–0.79) < BMI 0.81 (0.76–0.86) < cholesterol < 0.85 (0.79–0.90) < CRP 0.88 (0.84–0.92). We developed a novel index for discriminating patients with NAFLD named NAFLD Mark. AUC was jumped to 0.98 (0.93–0.99) when five markers were combined. The AUC of NAFLD mark for NAFLD detection was higher than the AUCs of seven common NAFLD indexes (0.44–0.86). Conclusions: The NAFLD mark is a non-invasive and highly sensitive and specific model for NAFLD diagnosis. [ABSTRACT FROM AUTHOR]

Chronic stress exposure is known to increase vulnerability to the expression of psychiatric disorders, such as depression. Clinical and preclinical evidences support the involvement of the microRNA-34 family in stress-related psychiatric conditions and in the regulation of stress responses. However, the mechanism and the multiple targets by which the microRNA-34 family can affect the stress response and stress-related behavioral alteration are not fully known. Here, with the aid of constitutive and conditional genetic strategy, we examined the role of microRNA-34 family in the expression of depression-like phenotype in mice induced by chronic stress exposure, and we identified their "in vivo" targets during the stressful challenge. We found that microRNA-34a, under chronic stress, is significantly up-regulated in the mouse raphe nuclei, where its recruitment is necessary to induce depression-like behavioral alterations and impact the function of the serotonergic system. Moreover, by next-generation RNA-seq of Ago-2-bound mRNAs, we identified genes that are targeted by microRNA-34a in response to chronic stress and that are likely to mediate its effects. [ABSTRACT FROM AUTHOR]

Highlights • IONPs with PEI–TPP outer layer were prepared successfully. • Nanocarriers with positive charge for carrying miR-34 were well-synthesized. • Outer shells can be soften by generated heat under a AMF. • Cytotoxicity of nanovector on BE–2M–17 cells was extremely low. • MYCN expression was successfully suppressed by miR-34a expression. Abstract Neuroblastoma accounts for about 6% of all cancers in children, with a 5–year survival rate of only 20–25%. The increased expressin of MYCN is associated with poor prognosis in patients with neuroblastoma. MicroRNA–34 (miR–34) may serve as a potential target for cancer treatment, owing to its function as an oncogene and tumor suppressor. In this study, positively charged magnetic nanocarriers comprising cross-linked polyethylenimine (PEI)–tripolyphosphate (TPP)–coated iron oxide nanoparticles (IONPs) were developed using co-precipitation method. These nanocarriers were capable of penetrating the cell wall and used for the delivery of miRNA–34a into the cells. The diffraction peak of synthesized magnetic nanocarriers at 2 θ = 35.44° corresponded to that of magnetite (Fe 3 O 4) (311), consistent with Joint Committee on Powder Diffraction Standards (JCPDS) database. The characteristic peaks at 3380, 1620, 2900, and 2840/cm corresponded to those of NH and − CH 2 − groups, indicating the successful coating of PEI. In addition, the small angle neutron scattering (SANS) spectra showed that the alternative magnetic field (AMF) triggered core heat generation, which softened the shells. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed the nontoxicity of these nanocarriers to BE–2–M17 cells. The expression of miR-34a was raised and the expression of MYCN, the target of miR-34a, was significantly suppressed. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

Recent studies show that microRNA-34 (miR-34) family is critical in the regulation of stress response also suggesting that it may contribute to the individual responsiveness to stress. We have recently demonstrated that mice carrying a genetic deletion of all miR-34 isoforms (triple knockout, TKO) lack the stress-induced serotonin (5-HT) and GABA release in the medial prefrontal cortex (mpFC) and basolateral amygdala (BLA), respectively. Here, we evaluated if the absence of miR-34 was also able to modify the stress-coping strategy in the forced swimming test. We found that the blunted neurochemical response to stress was associated with lower levels of immobility (index of active coping behavior) in TKO compared to WT mice. Interestingly, among the brain regions mostly involved in the stress-related behaviors, the miR-34 displayed the strongest expression in the dorsal raphe nuclei (DRN) of wild-type (WT) mice. In the DRN, the corticotropin-releasing factor receptors (CRFR) 1 and 2, contribute to determine the stress-coping style and the CRFR1 is a target of miR-34. Thus, we hypothesized that the miR-34-dependent modulation of CRFR1 expression may be involved in the DRN regulation of stress-coping strategies. In line with this hypothesis, we found increased CRFR1 levels in the DNR of TKO compared to WT mice. Moreover, infusion of CRFR1 antagonist in the DRN of TKO mice reverted their behavioral and neurochemical phenotype. We propose that miR-34 modulate the mpFC 5-HT/BLA GABA response to stress acting on CRFR1 in the DRN and that this mechanism could contribute to determine individual stress-coping strategy. [ABSTRACT FROM AUTHOR]

The exposure to extremely low-frequency magnetic fields (ELF-MFs) has been associated to increased risk of neurodegenerative diseases, although the underlying molecular mechanisms are still undefined. Since epigenetic modulation has been recently encountered among the key events leading to neuronal degeneration, we here aimed at assessing if the control of gene expression mediated by miRNAs, namely miRs-34, has any roles in driving neuronal cell response to 50-Hz (1 mT) magnetic field in vitro. We demonstrate that ELF-MFs drive an early reduction of the expression level of miR-34b and miR-34c in SH-SY5Y human neuroblastoma cells, as well as in mouse primary cortical neurons, by affecting the transcription of the common pri-miR-34. This modulation is not p53 dependent, but attributable to the hyper-methylation of the CpG island mapping within the miR-34b/c promoter. Incubation with N-acetyl-l-cysteine or glutathione ethyl-ester fails to restore miR-34b/c expression, suggesting that miRs-34 are not responsive to ELF-MF-induced oxidative stress. By contrast, we show that miRs-34 control reactive oxygen species production and affect mitochondrial oxidative stress triggered by ELF-MFs, likely by modulating mitochondria-related miR-34 targets identified by in silico analysis. We finally demonstrate that ELF-MFs alter the expression of the α-synuclein, which is specifically stimulated upon ELF-MFs exposure via both direct miR-34 targeting and oxidative stress. Altogether, our data highlight the potential of the ELF-MFs to tune redox homeostasis and epigenetic control of gene expression in vitro and shed light on the possible mechanism(s) producing detrimental effects and predisposing neurons to degeneration. [ABSTRACT FROM AUTHOR]

Gastric cancer is a major cause of cancer mortality worldwide, with a low survival rate for patients with advanced forms of the disease. Over the recent decades, the investigation of the pathophysiological mechanisms of tumourigenesis has opened promising avenues to understand some of the complexities of cancer treatment. However, tumour regeneration and metastasis impose great difficulty for gastric cancer cure. In recent years, cancer stem cells - a small subset of tumour cells in many cancers - have become a major focus of cancer research. Cancer stem cells are capable of selfrenewal and are known to be responsible for tumour initiation, metastasis, therapy resistance and cancer recurrence. Recent studies have revealed the key role of microRNAs - small noncoding RNAs regulating gene expression - in these processes. MicroRNAs play crucial roles in the regulation of a wide range of biological processes in a post-transcriptional manner, though their expression is dysregulated in most malignancies, including gastric cancer. In this article, we review the consequences of aberrant expression of microRNA-34 in cancer and cancer stem cells, with a specific focus on the miR-34 dysregulation in gastric cancer and gastric cancer stem cells. We address the critical effects of the aberrant expression of miR-34 and its target genes in maintaining cancer stem cell properties. Information collection and discussion about the advancements in gastric cancer stem cells and microRNAs can be useful for providing novel insights into patient treatment. [ABSTRACT FROM AUTHOR]

MicroRNA-34 (miR-34), in particular miR-34a, has a negative regulatory effect on osteosarcoma cell proliferation, migration and invasion. Notably, it is also a post-transcriptional regulatory factor of (sex determining region Y)-box 2 (Sox-2), which is required for osteosarcoma cell self-renewal and tumorigenesis. As a direct regulator of Sox-2, miR-34a has been hypothesized to be greatly associated with the regulation of malignancies in osteosarcoma. To investigate the role of miR-34a in the malignancies of osteosarcoma, reverse transcription-quantitative polymerase chain reaction was performed to detect the expression level of miR-34a in osteospheres. The results revealed that the miR-34a, b and c were suppressed in osteosarcoma stem-like cells (OSCs) and osteospheres. The introduction of miR-34a mimics and short hairpin (sh)RNA targeting Sox-2 mRNA (shSox-2) in human OSCs markedly reduced their transformation properties in vitro and their capacity to form tumors in soft agar. Furthermore, the epigenetic expression of miR-34a and shSox-2 inhibited the expression of the stem cell marker, stem cell antigen-1 and led to the failure of osteosphere formation, respectively. The data of the present study indicated that the inhibitory role of miR-34a on tumor growth and metastasis of osteosarcoma may function by reducing the maintenance of osteosphere self-renewal capacity, elimination of tumorigenic ability and invasion of osteosarcoma in vitro. These findings may provide the basis for a novel therapeutic target of osteosarcomas based on inducing the expression of miR-34a. [ABSTRACT FROM AUTHOR]

Background Skin aging is a process of structural and compositional remodeling that can be manifested as wrinkling and sagging. Remarkably, the dermis plays a dominant role in the process of skin aging. Recent studies suggest that microRNAs (miRNAs) may play a role in the regulation of gene expression in organism aging. However, studies about age-related miRNAs in human skin remain limited. Objective To obtain an overall view of miRNAs expression in human aged dermis by comparison of dermis samples between young and elderly, construct the miRNA-gene-network and reveal the pivotal miRNAs in the regulatory network. Methods Human dermis tissue was obtained from 12 donors, including 6 of young group and 6 of elderly one. The miRNA microarray and data analysis were performed. Target genes of differentially expressed miRNAs were predicted, followed by a gene ontology and pathway enrichment analysis. A miRNA-gene-network was then constructed, and the pivotal miRNAs in the network was revealed. Primary human dermal fibroblasts (HDFs) were isolated, and the cellular senescence was induced by serial passaging. Alteration in the expression of miRNAs between young and senescent fibroblasts was evaluated by real-time quantitative RT-PCR. MiR-34b-5p mimics were transfected into primary HDFs. Subsequent cell cycle analysis was performed and expression level of COL1A1, elastin and MMP-1 were evaluated. Results The expression of a total of 40 miRNAs (25 upregulated and 15 downregulated) was found to be significantly altered in aged dermis compared with young dermis. Real-time quantitative PCR results confirmed the differential expression of miR-34 family and miR-29 family between young and aged dermis. A computational approach demonstrated that predicted target genes of the miRNA profile were found to be mainly involved in processes including cell adhesion, collagen synthesis, positive or negative regulation of transcription, as well as pathways such as insulin signaling pathway, ErbB (Erythroblastic Leukemia Viral Oncogene Homolog) signaling pathway and Focal adhesion pathway. The miRNA-Gene-Network revealed that miR-34 family, miR-29 family and miR-424 may play a dominant role in the regulatory network. A similar miRNA alteration was observed in senescent fibroblasts in vitro, and the age-related miRNA profile may interact with p16 pathway to regulate the fibroblasts’ senescence. Additionally, transfection of miR-34b-5p mimics induced cell cycle arrest in HDFs, decreased the expression of both COL1A1 and elastin and increased MMP-1 expression. Conclusion The miR-34 family and miR-29 family expressed differentially in young and aged dermis. MiR-34 in HDFs modulated the cell function and expression of MMP-1, COL1A1 and elastin. The miRNAs may play critical roles in affecting dermis aging. [ABSTRACT FROM AUTHOR]

Recently many studies have focused on the microRNA-34 (miR-34) family expression in various cancers; nevertheless, the controversial results of these studies still exist in identifying miR-34 members as new biomarkers of cancers. Therefore, we carried out this comprehensive meta-analysis of published studies that compared the miR-34 family expression profiles between cancer tissues and paired neighboring noncancerous tissues to systemically evaluate the findings globally and address the inconsistencies of pertinent literatures. The data included in this article were collected from Embase, PubMed and Web of Science up to December 2013. To overcome the difficulties that many raw data were unavailable and study methods were different, a vote-counting strategy was adopted to identify consistent markers in our analysis. Ultimately, a total of 23 cancers were reported in the 61 eligible studies, of which 46 studies provided fold-change value information. In the consistently reported cancer types, non-small cell lung cancer (NSCLC), glioma and nasopharyngeal carcinoma (NPC) ranked at the top with down-regulated feature. Cervical neoplasm was consistently reported to be over-expressed in the panel of each member of miR-34s. Subgroup analysis of miR-34 family expression demonstrated that colorectal cancer (CRC), gastric cancer (GC), hepatocellular carcinoma (HCC) and prostate cancer (PCa) were most frequently reported with inconsistent regulations. Our meta-analysis showed that miR-34 family members could be expected to become potential diagnostic and prognostic biomarkers in some types of human cancers. Further well-designed and larger sample studies are surely warranted to identify the role of the miR-34 family in the occurrence and development of tumors. [ABSTRACT FROM AUTHOR]

As the most common primary bone neoplasm, osteosarcoma is highly aggressive and represents a high risk to human health. Biological agents, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), are considered promising therapeutic strategies for osteosarcoma. The current issue limiting the application of TRAIL gene therapy is that normal cells are also affected due to the lack of tumor selectivity. The present study aimed to employ the miRNA response elements (MREs) of microRNA (miR)-34 and miR-122, which are tumor suppressors, to enable the selective expression of TRAIL by adenoviral vectors in osteosarcoma cells. The results revealed that miR-34 and miR-122 were underexpressed in osteosarcoma tissues, compared with normal tissues. The MREs of miR-34 and miR-122 ensured that the luciferase gene was expressed selectively in osteosarcoma cells. Adenovirus (Ad)-TRAIL-34-122, which expressed TRAIL in an miR-34 and miR-122-regulated manner, selectively expressed TRAIL in the osteosarcoma cells assessed, which was detected using reverse transcription quantitative polymerase chain reaction, immunoblotting and ELISA. Apoptosis and cytotoxicity were also detected in the osteosarcoma cells, compared with the normal cells. Animal experiments further indicated that Ad-TRAIL-34-122 was able to reduce the growth of osteosarcoma xenografts without toxicity to the liver. In conclusion, the present study identified a novel miRNA-regulated biological cancer therapy against osteosarcoma, which is tumor selective and may be promising for future clinical treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nano-sized MNCs corresponding to Fe 3 O 4 were successfully prepared. • AMF triggered core heat of MNCs which subsequently softened the shell. • The nanocarrier could be controlled by an external magnetic field. • Magnetofection efficiency into negatively charged cells was significantly improved. • Expression of miR-34a led to the suppression of MYCN protein. Neuroblastoma, which accounts for almost 6% of all cancers in infants, originates from the sympathoadrenal progenitor cells within the neural crest. Approximately 25 % of neuroblastoma cases result from the amplification of the MYC-related oncogene MYCN, thus leading to high disease risk and poor prognosis; hence, studies focusing on the inhibition of MYCN are indispensable. Interestingly, microRNA-34 (miR-34) is a prospective candidate for cancer therapy because of its oncogenic and tumor-suppressing ability. This study presents the synthesis, characterization, and application of cationic magnetic nanocomposites (MNCs) comprising branched polyethylenimine (PEI)-coated iron oxide nanoparticles (IONPs). These positively charged MNCs possess the ability to penetrate the negatively charged cell wall for the delivery of miR-34a molecules into cancerous cells. The characteristic peaks at 3380, 1620, 2900, and 2840 cm−1 corresponding to −NH− and −CH 2 − groups suggest successful coating of PEI on the surface of IONPs. The X-ray powder diffraction (XRPD) peak of the prepared MNCs at 2 θ = 35.44° resembled that of magnetite (Fe 3 O 4 , (311)). The transfection efficiency was enhanced through a magnetic field that enabled a very rapid concentration of the completely delivered vector dose onto cells. Additionally, the results of small-angle neutron scattering (SANS) revealed that core heat was generated and subsequently led to shell softening, which was activated by an alternative magnetic field (AMF). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that MNCs did not exhibit any significant toxicity against the tested cells. The increased amplification of miR-34a led to the suppression of the MYCN protein, which consequently inhibited the growth of neuroblastoma cells. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA)-34 family (miR-34s), including miR-34a/b/c, is the most well studied non-coding RNAs that regulate gene expression post-transcriptionally. The miR-34s mediates the tumor suppressor function of p53 in the pathogenesis of breast cancer by targeting different oncogenes. This review focuses on the anti-oncogenic regulation of the miR-34s, emphasizing the major signaling pathways that are involved in the modulation of miR-34s in breast cancer. Moreover, it highlights how epigenetic modification by the p53/miR-34s axis regulates the proliferation, invasiveness, chemoresistance, and sternness of breast cancer. A better understanding of the molecular mechanisms of miR-34s will open new opportunities for the development of novel therapeutic strategies and define a new approach in identifying potential biomarkers for early diagnosis of breast cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Gastric cancer is a major cause of cancer mortality worldwide, with a low survival rate for patients with advanced forms of the disease. Over the recent decades, the investigation of the pathophysiological mechanisms of tumourigenesis has opened promising avenues to understand some of the complexities of cancer treatment. However, tumour regeneration and metastasis impose great difficulty for gastric cancer cure. In recent years, cancer stem cells - a small subset of tumour cells in many cancers - have become a major focus of cancer research. Cancer stem cells are capable of self-renewal and are known to be responsible for tumour initiation, metastasis, therapy resistance and cancer recurrence. Recent studies have revealed the key role of microRNAs - small noncoding RNAs regulating gene expression - in these processes. MicroRNAs play crucial roles in the regulation of a wide range of biological processes in a post-transcriptional manner, though their expression is dysregulated in most malignancies, including gastric cancer. In this article, we review the consequences of aberrant expression of microRNA-34 in cancer and cancer stem cells, with a specific focus on the miR-34 dysregulation in gastric cancer and gastric cancer stem cells. We address the critical effects of the aberrant expression of miR-34 and its target genes in maintaining cancer stem cell properties. Information collection and discussion about the advancements in gastric cancer stem cells and microRNAs can be useful for providing novel insights into patient treatment.

Background: Many patients with non-small-cell lung cancer (NSCLC) still develop tumor metastasis and recurrence after pulmonary resection and are the primary causes of lung cancer treatment failure and death. MicroRNAs (miRs) have central roles during tumor metastasis and many miR genes are potentially subjected to control by DNA methylation in multiple tumor types. Recently, miR-34 and miR-124 have been demonstrated as potential regulators of the metastasis process in several cancer types., Materials and Methods: We studied the methylation status of miR-34 and miR-124 families in 157 patients with NSCLC using methylation-specific polymerase chain reaction and evaluated the clinical effect of their methylation on the patients' prognosis., Results: Methylation was detected in 30.6% for miR-34a, 40.8% for miR-34b/c, 30.6% for miR-124-1, 49.7% for miR-124-2, and 51.6% for miR-124-3 in NSCLC tissue. miR-34b/c methylation was significantly associated with age, gender, smoking status, histologic type, and pathologic stage. miR-34b/c, miR-124-2, and miR-124-3 methylation were significantly associated with worse survival in all patients (adjusted hazard ratio [HR adj ] for miR-34b/c, 3.34; 95% confidence interval [CI], 1.95-5.74; P < .0001; HR adj for miR-124-2, 1.99; 95% CI, 1.19-3.32; P = .009; and HR adj for miR-124-3, 2.10; 95% CI, 1.24-3.55; P = .006). When miR-34b/c and miR-124-3 methylation were combined, overall survival decreased as the number of methylations increased (P trend  < .0001)., Conclusion: These findings suggest that miR-34 and miR-124 loci methylation could be a tumor-associated frequent event during NSCLC tumorigenesis and could be used as powerful markers for the prognosis of patients with NSCLC., (Copyright © 2016 Elsevier Inc. All rights reserved.)