[Retracted] miR­613 suppresses migration and invasion in esophageal squamous cell carcinoma via the targeting of G6PD.

[This retracts the article DOI: 10.3892/etm.2020.8540.].

Differential roles of highly expressed PFKFB4 in colon adenocarcinoma patients.

Colon adenocarcinoma (COAD) is a common malignant tumor, and the role of the protein PFKFB4 in glycolysis and pentose phosphate pathways is crucial. Researchers investigated the clinical significance of PFKFB4 in COAD by studying its expression in 79 tissue samples using immunohistochemistry. We found that PFKFB4 expression was significantly higher in COAD patients, particularly in the sigmoid colon. Interestingly, high PFKFB4 expression was associated with both improved overall survival (OS) and worse progression-free survival (PPS) in COAD patients. Further analysis revealed that genes associated with PFKFB4 were linked to various metabolic pathways, including amino acid biosynthesis, glycolysis, gluconeogenesis, glucose metabolism, and inflammatory response. PFKFB4 expression also showed correlations with the infiltration of different immune cell types in COAD patients, such as CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), macrophages, neutrophils, dendritic cells, active mast cells, and resting NK cells. Overall, the relationship between PFKFB4 expression and the prognosis of COAD is complex and diverse, possibly playing different roles at different stages of the disease. Moreover, its mechanism might involve interactions with various metabolic pathways and immune infiltration in the tumor microenvironment. These findings provide valuable insights into the potential role of PFKFB4 as a biomarker or therapeutic target in COAD.

Cancer-Associated Fibroblasts Affect Tumor Metabolism and Immune Microenvironment in Gastric Cancer and Identification of Its Characteristic Genes.

Background: Cancer-associated fibroblasts (CAFs) have reported widely involved in cancer progression. However, its underlying mechanism in gastric cancer is still not clarified. Methods: The data used in this study were all downloaded from the Cancer Genome Atlas database. R software and the R packages were used for all the analyses. Results: In our study, we first quantified the CAFs infiltration using the ssGSEA algorithm. The clinical correlation result showed that CAFs were associated with a worse prognosis and clinical features. Pathway enrichment also indicated several oncogenic pathways in GC patients with high CAFs infiltration, including epithelial-mesenchymal transition (EMT), myogenesis, allograft rejection, the inflammatory response, and IL2/STAT5 signaling. Furthermore, FNDC1 and RSPO3 were identified as the characteristic genes of CAFs through two machine learning algorithms, LASSO logistic regression and SVM-RFE. The following analysis showed that FNDC1 and RSPO3 were associated with more progressive clinical features and had a good prediction efficiency of the CAFs infiltration status in GC patients. Pathway enrichment and genomic instability were performed to explore the underlying mechanisms of FNDC1 and RSPO3. Immune infiltration analysis showed that CAFs were positively correlated with M2 macrophages. Moreover, we found that the GC patients with low CAFs infiltration were more sensitive to immunotherapy. Also, the CAFs, FNDC1, and RSPO3 could generate a certain effect on the sensitivity of doxorubicin, mitomycin, and paclitaxel. Conclusions: In summary, our study comprehensively investigated the role of CAFs in GC, which might be associated with immunotherapy sensitivity. Meanwhile, FNDC1 and RSPO3 were identified as the underlying targets of GC.

Spatial characteristics of change trends of air pollutants in Chinese urban areas during 2016-2020: The impact of air pollution controls and the COVID-19 pandemic.

Air pollution is a threat to public health in China, and several actions and plans have been implemented by Chinese authorities in recent years to mitigate it. This study examined the spatial distribution of changes in urban air pollutants (UAP) in 336 Chinese cities from 2016 to 2020 and their responses to air pollution controls and the COVID-19 pandemic. Based on the harmonic model, decreases in fine particles (PM2.5), inhalable particles (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO) levels were found in 90.7%, 91.9%, 75.2%, 94.3%, and 88.7% of cities, respectively, while an increase in ozone (O3) was found in 87.2% of cities. Notable spatial heterogeneity was observed in the air pollution trends. The greatest improvement in air quality occurred mainly in areas with poor air quality, such as Hebei province and its surrounding cities. However, some areas (i.e., Yunnan and Hainan provinces) with good air quality showed a worsening trend. During the 13th Five-Year Plan period (2016-2020), the remarkable effects of PM2.5 and SO2 pollution control plans were confirmed. Additionally, economic growth in 74.2% of the Chinese provinces decoupled from air quality after implementing pollution control measures. In 2020, several Chinese cities were locked down to reduce the spread of COVID-19. Except for SO2, the national air pollution in 2020 improved to a greater extent than that in 2016-2019; In particularly, the contribution of simulated COVID-19 pandemic to NO2 reduction was 66.7%. Overall, air pollution control actions improved urban PM2.5, PM10, SO2, and CO, whereas NO2 was reduced primarily because of the COVID-19 pandemic.

Lpar1-mediated Effects in Endothelial Progenitor Cells Are Crucial for Lung Repair in Acute Respiratory Distress Syndrome/Acute Lung Injury.

Acute respiratory distress syndrome/acute lung injury (ARDS/ALI) involves acute respiratory failure characterized by vascular endothelial and lung alveolar epithelial injury. Endothelial progenitor cells (EPCs) can mediate vasculogenesis. However, the limitations of EPCs, such as low survival and differentiation, are believed to inhibit the effectiveness of autologous cell therapies. This study demonstrated that lysophosphatidic acid (LPA), a bioactive small molecule without immunogenicity, is involved in the survival and antiapoptotic effects in human umbilical cord mesenchymal stem cells. This study aimed to explore whether LPA improves the survival of EPCs, enhancing the cellular therapeutic efficacy in ARDS, and these results will expand the application of LPA in stem cells and regenerative medicine. LPA promoted the colony formation, proliferation, and migration of EPCs and upregulated the expression of vascular endothelial-derived growth factor (VEGF) in EPCs. LPA pretreatment of transplanted EPCs improved the therapeutic effect by increasing EPC numbers in the rat lungs. LPA enhanced EPC proliferation and migration through Lpar1 coupled to Gi/o and Gq/11, respectively. Activation of extracellular signal-related kinase 1/2, or ERK1/2, was related to LPA-induced EPC proliferation but not migration. LPA/Lpar1-mediated Gi/o protein was also shown to be involved in promoting VEGF expression and inhibiting IL-1α expression in EPCs. Low LPA concentrations are present after lung injury; thus, the restoration of LPA may promote endothelial cell homeostasis and lung repair in ARDS. Inhalation of LPA significantly promoted the homing of endogenous EPCs to the lung and reduced lung injury in both rats with LPS-induced ALI and Streptococcus pneumoniae-infected mice. Taken together, these data indicated that LPA/Lpar1-mediated effects in EPCs are involved in maintaining endothelial cell homeostasis and lung tissue repair under physiological conditions.

Six MicroRNA Prognostic Models for Overall Survival of Lung Adenocarcinoma.

Objective: The purpose of this study is to screen for microRNAs (miRNAs) associated with the prognosis of lung adenocarcinoma (LUAD) and to explore its prognosis and effects on the tumor microenvironment in patients with LUAD. Methods: Gene expression data, miRNA expression data, and clinical data for two different databases, TCGA-LUAD and CPTAC-3 LUAD, were downloaded from the GDC database. The miRNA prognosis of LUAD was filtered by the Cox proportional hazard model and the Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The performance of the model was validated by time-dependent receiver operating characteristics (ROC) curves. Possible biological processes associated with the miRNAs target gene were analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the prognostic model was scored by risk, divided into high- and low-risk groups by median, and the differences in the immersion level of 21 immune cells in the high- and low-risk groups were assessed. To gain a deeper understanding of the underlying mechanism behind the model, the two most important miRNAs in the model, miR-195-3p and miR-5571-5p, were selected for HPA database validation and ceRNA network construction. Results: Of the 209 variance expressions identified in the screening analysis, 145 were upregulated and 64 were downregulated by miRNAs. The prognostic models of six miRNA genes were obtained: miR-195-3p, miR-5571-5p, miR-584-3p, miR-494-3p, miR-4664-3p, and miR-1293. These six genes were significantly associated with survival rates in LUAD patients. In particular, miR-1293, miR-195-3p, and miR-5571-5p are highly correlated with OS. The higher expression of miR-195-3p and miR-5571-5p, the better survival of LUAD OS is, and these two miRNA expressions contribute the most to the model. Finally, after sorting the risk scores calculated from low to high using the prognostic model, the patients with higher scores had shorter survival time and higher frequency of death, and there were significant differences in the immersion levels of 21 immune cells in the high- and low-risk groups. ceRNA network analysis found that TM9SF3 was regulated by miR-195-3p and was highly expressed in the tissues of LUAD patients, and the prognosis of the patients was poor. Conclusions: miR-195-3p, miR-5571-5p, miR-584-3p, miR-494-3p, miR-4664-3p, and miR-1293 may be used as new biomarkers for prognosis prediction of LUAD. Our results also identified a lncRNA MEG3/miR-195-3p/RAB1A/TM9SF3 regulatory axis, which may also play an important role in the progression of LUAD. Further study needs to be conducted to verify this result.

[Spatial characteristics and source apportionment of urban environmental black carbon concentrations based on mobile monitoring]. / 基于移动监测的城市环境大气黑碳浓度空间特征及来源解析.

Black carbon (BC) is an important component of airborne fine particulate matter, with significant impacts on global climate change and human health. Taking Minhang District of Shanghai as the study area, a microaethalometer (MA200) and GPS were installed on the electric taxi to form a mobile observation platform to identify the spatial distribution and hot spots of atmospheric BC in urban environment. We analyzed the sources and influencing factors of BC. The results showed that the overall characteristics of the spatial distribution pattern of near surface atmospheric BC in Minhang District of Shanghai were high in the north and low in the south. The average BC concentration was (4.11±4.87) µg·m-3. The average concentrations of BC in working days and non-working days were (4.22±1.49) and (3.52±2.26) µg·m-3. The variability of BC concentration in the high value area was large, indicating that the increases of BC concentration in mobile observation were related to traffic accidents in the road section. In addition to human activities, large-scale dense vegetation might inhibit BC diffusion. The Absorption ngström Exponent (AAE) was (0.82±0.54), which was closer to that of fossil fuel combustion. The contributions of fossil fuel emissions, biomass combustion, and mixed sources to BC sources were 67.5%, 4.9% and 27.6%, respectively.

Low-cost polymer-film spiral inertial microfluidic device for label-free separation of malignant tumor cells.

We developed a low-cost polymer-film spiral inertial microfluidic device for the effective size-dependent separation of malignant tumor cells. The device was fabricated in polymer films by rapid laser cutting and chemical bonding. After fabricating the prototype device, the separation performance of our device was evaluated using particles and cells. The effects of operational flow rate, cell diameter, and cell concentration on the separation performance were explored. Our device successfully separated tumor cells from polydisperse white blood cells according to their different migration modes and lateral positions. Then, the separation of rare cells was carried out using the high-concentration lysed blood spiked with 200 tumor cells. Experimental results showed that 83.90% of the tumor cells could be recovered, while 99.87% of white blood cells could be removed. We successfully employed our device for processing clinical pleural effusion samples from patients with advanced metastatic breast cancer. Malignant tumor cells with an average purity of 2.37% could be effectively enriched, improving downstream diagnostic accuracy. Our device offers the advantages of label-free operation, low cost, and fast fabrication, thus being a potential tool for effective cell separation.

Identification of Potential Prognostic and Predictive Biomarkers for Immune-Checkpoint Inhibitor Response in Small Cell Lung Cancer.

BACKGROUND Immune-checkpoint inhibitors have propelled the field of therapeutics for small cell lung cancer (SCLC) treatment, but are only beneficial to some patients. The objective of this study was to identify valid biomarkers for good potential response to immunotherapy. MATERIAL AND METHODS We performed an integrated analysis of the available datasets from the Gene Expression Omnibus (GEO) projects, Cancer Cell Line Encyclopedia (CCLE), TISIDB database, and Lung Cancer Explorer (LCE) database. Six prognosis-related genes (MCM2, EZH2, CENPK, CHEK1, CDKN2A, and EXOSC2) were identified utilizing the meta workflow of data analysis methods. We performed subclass mapping to compare their expression profiles to other datasets of patients who responded to immunotherapy. A drug sensitivity predictive model was used to predict the chemotherapeutic response to cisplatin and etoposide. RESULTS Our results showed that the expression of the 6 key genes was significantly associated with the overall survival of patients with SCLC. Lower expression of these 6 genes was correlated to the response to anti-PD-1 treatment. Additionally, low expression of MCM2, EZH2, CENPK, and CHEK1 was correlated with increased sensitivity to cisplatin, but not etoposide. CONCLUSIONS Overall, our data showed that MCM2, EZH2, CENPK, CHEK1, CDKN2A, and EXOSC2 are potential prognostic and predictive biomarkers for response to immune-checkpoint inhibitor treatment in patients with SCLC. Further studies with large sample sizes are required to validate our findings and to explore the detailed mechanisms underlying the role of these genes in SCLC.

[Changes and Potential Sources of Atmospheric Black Carbon Concentration in Shanghai over the Past 40 Years Based on MERRA-2 Reanalysis Data].

As an important component of atmospheric aerosols, black carbon (BC) has a great influence on the regional and global radiation balance, climate, and human health due to its small particle size, large specific surface area, and radiative forcing potential. Here, the spatio-temporal characteristics of atmospheric BC were investigated based on modern-era retrospective analysis for research and applications version 2 (MERRA-2) reanalysis data and ground observation data during 1980-2019 in Shanghai, a highly urbanized city in mainland China. The influences of local emissions and regional transmission on regional-scale BC concentrations were examined using the M-K trend test, backward trajectory analysis, and the potential source contribution function (PSCF). The results showed that:① MERRA-2 BC and ground observation datasets showed good consistency (R∈[0.68, 0.72]), indicating that MERRA-2 reanalysis data can be used to reveal long-term changes in ground-level atmospheric BC concentrations; ② Atmospheric BC concentrations in Shanghai over the past 40 years can be divided into three stages:a "low value" stage of slow growth[1980-1986, (1.75±0.17) µg·m-3], a relatively stable "median value" stage[1987-1999, (2.18 ±0.07) µg·m-3], and a fluctuating "high value" stage[2000-2019, (3.07±0.31) µg·m-3]. Seasonally, Shanghai's BC concentrations generally show a "U" pattern with low concentrations in summer and high concentrations in winter. As a result of black carbon emissions from marine diesel engines and other engines used for water transportation, a small peak also occurs in July; ③ The diagnostic quality ratio of air pollutants and the bivariate correlation analysis[R(BC-NO2)>R(BC-CO)>R(BC-SO2)] indicated that traffic emissions were the main sources of atmospheric BC in Shanghai, especially by heavy diesel vehicles; ④ The backward trajectory and PSCF analyses found that the air mass of Shanghai in summer was dominated by a clean sea breeze, accounting for 77.18%. In contrast, during the other seasons, more than 50% of the air mass came from the north. The potential source regions of atmospheric BC in Shanghai are mainly distributed in eastern China, expanding outwards and centering on the Yangtze River Delta, and the expansion direction is consistent with the directions of the backward trajectories.

Impact of the COVID-19 pandemic on air pollution in Chinese megacities from the perspective of traffic volume and meteorological factors.

During 2020, the COVID-19 pandemic resulted in a widespread lockdown in many cities in China. In this study, we assessed the impact of changes in human activities on air quality during the COVID-19 pandemic by determining the relationships between air quality, traffic volume, and meteorological conditions. The megacities of Wuhan, Beijing, Shanghai, and Guangzhou were selected as the study area, and the variation trends of air pollutants for the period January-May between 2016 and 2020 were analyzed. The passenger volume of public transportation (PVPT) and the passenger volume of taxis (PVT) along with data on precipitation, temperature, relative humidity, wind speed, and boundary layer height were used to identify and quantify the driving force of the air pollution variation. The results showed that the change rates of fine particulate matter (PM2.5), NO2, and SO2 before and during the lockdown in the four megacities ranged from -49.9% to 78.2% (average: -9.4% ± 59.3%), -55.4% to -32.3% (average: -43.0% ± 9.7%), and - 21.1% to 11.9% (average: -10.9% ± 15.4%), respectively. The response of NO2 to the lockdown was the most sensitive, while the response of PM2.5 was smaller and more delayed. During the lockdown period, haze from uninterrupted industrial emissions and fireworks under the effect of air mass transport from surrounding areas and adverse climate conditions was probably the cause of abnormally high PM2.5 concentrations in Beijing. In addition, the PVT was the most significant factor for NO2, and meteorology had a greater impact on PM2.5 than NO2 and SO2. There is a need for more national-level policies for limiting firework displays and traffic emissions, as well as further studies on the formation and transmission of secondary air pollutants.

Circular RNA circ_0008274 upregulates granulin to promote the progression of hepatocellular carcinoma via sponging microRNA -140-3p.

Circular RNA (circRNA) features prominently in the progression of hepatocellular carcinoma (HCC), of which the biological function and potential mechanism of circ_0008274 in HCC are obscure. The present study aims to explore circ_ 0008274's biological functions and underlying mechanisms in HCC. The expressions of circ_0008274, miR-140-3p and Granulin (GRN) mRNA in HCC tissues and cells were investigated by quantitative real-time polymerase chain reaction. Besides, GRN protein expression was measured by Western blot. Furthermore, chi-square test was used to probe the interrelation between circ_0008274 expression and clinicopathological parameters. In addition, cell counting kit-8 (CCK-8) and EdU assays were applied to detect cell proliferation. Moreover, transwell assay was used to detect cell migration and invasion. What's more, bioinformatics prediction, dual-luciferase reporter gene assay and RNA Immunoprecipitation experiments were used to corroborate the targeting interrelations among circ_0008274, miR-140-3p and GRN. Herein we reported that circ_0008274 was highly expressed in HCC, and its high expression enhanced the proliferation, migration, and invasion of HCC cells, while depleting circ_0008274 inhibited the malignant biological behaviors of HCC cells. Mechanistically, circ_0008274 upregulates GRN expressions via adsorbing miR-140-3p to expedite the progression of HCC.

ROR promotes the proliferation and migration of esophageal cancer through regulating miR-145/LMNB2 signal axis.

OBJECTIVE: LMNB2 is a protein that belongs to the RAB family. It is correlated with the tumorigenesis and development of several human cancers. The effect of LMNB2 on esophageal cancer (EC) has not yet been reported. The previous study showed that lncRNA ROR could promote the proliferation of EC. The current study aimed at exploring the correlation between ROR with LMNB2 and the role of ROR and LMNB2 in proliferation and migration of EC. METHODS: This study performed dual luciferase reporter assay to evaluate the binding between miR-145 and ROR as well as miR-145 and LMNB2. Gene expression in EC tissues and cells were detected using quantitative real-time PCR (qRT-PCR) assay. The effect of ROR or miR-145 on LMNB2 expression was detected using western blot (WB) assay. Cells proliferation was detected by CCK8 and clone formation assay. Transwell and wound healing assay were carried out to determine the cells migration. Mouse xenograft assay was performed to detect the effect of LMNB2 on tumor growth in vivo. RESULTS: This study demonstrated that miR-145 directly targets ROR and LMNB. ROR and LMNB2 were up-regulated and miR-145 was down-regulated in EC tissues and cells. The proliferation and migration of EC cells were promoted by overexpression of of ROR or LMNB2. MiR-145 was capable of reversing the effect of ROR. The results also determined that down-regulation of LMNB2 had inhibitory effects and up-regulation of LMNB2 had catalytic effects on tumor growth in vivo. CONCLUSION: LMNB2 which is regulated by ROR and miR-145 was highly expressed in EC and promoted the proliferation and migration of EC in vitro and in vivo. The study suggests that ROR and LMNB2 could be potentially the therapeutic targets of EC.

miR-613 suppresses migration and invasion in esophageal squamous cell carcinoma via the targeting of G6PD.

Esophageal squamous cell carcinoma (ESCC) is a common cancer in China and has a high mortality rate. MicroRNAs (miRs) are a family of post-transcriptional regulators, which negatively regulate target gene expression. miR-613 has been revealed to be a diagnostic and prognostic biomarker in ESCC. However, the role of miR-613 in ESCC remains unclear. In the present study, miR-613 expression was identified to be reduced in tumor tissues in comparison with corresponding adjacent normal tissues. TargetScan and a dual-luciferase reporter assay verified glucose-6-phosphate dehydrogenase (G6PD) as a direct target of miR-613. In contrast with miR-613, G6PD expression was increased in tumor tissues compared with matched healthy tissues. Furthermore, overexpression of miR-613 inhibited cell migration and invasion of Eca109 cells compared with controls, while G6PD overexpression reversed the inhibition induced by miR-613, as determined by wound healing and Transwell assays. In addition, miR-613 overexpression decreased the mRNA and protein expression of G6PD, matrix metalloproteinase (MMP)2 and MMP9, and reduced the phosphorylation of signal transducer and activator of transcription 3 (STAT3) compared with controls, while G6PD reversed the effects of miR-613. However, miR-613 and G6PD did not affect the expression of STAT3. In conclusion, the aforementioned results suggest that miR-613 targets G6PD to suppress ESCC cell migration and invasion through reduced MMP2 and MMP9 expression and inactivation of the STAT3 signaling pathway. Thus, the present study may provide a new molecular foundation for treatment of ESCC.

High intratumoral expression of eIF4A1 promotes epithelial-to-mesenchymal transition and predicts unfavorable prognosis in gastric cancer.

Gastric cancer is an important health problem, being the fifth most common cancer and the third leading cause of cancer-related death worldwide. Aberrant protein translation contributes to the oncogenesis and development of cancers, and upregulation of translation initiation factor eIF4A1 has been observed in several kinds of malignancies. However, the role of eIF4A1 in gastric cancer progression remains unclear. In this study, we found that the expression of eIF4A1, a component of translation initiation complex, was increased in gastric cancer. High expression of eIF4A1 was positively associated with poor tumor differentiation, late T stage, lymph node metastasis, advanced TNM stage, and poor prognosis in patients with gastric cancer. Overexpression of eIF4A1 promoted the migration and invasion of gastric cancer cells in vitro and enhanced tumor metastasis in nude mice model. Mechanism studies revealed that eIF4A1 induced epithelial-to-mesenchymal transition (EMT) of gastric cancer cells through driving the translation of SNAI1 mRNA. Together, these findings indicate that eIF4A1 promotes EMT and metastasis of gastric cancer and suggest that eIF4A1 is a potential target for the adjuvant therapy for gastric cancer patients.

Immunomodulatory effects of chemotherapy on blood lymphocytes and survival of patients with advanced non-small cell lung cancer.

A better understanding of the immune profile of non-small cell lung cancer (NSCLC) and the immunomodulatory impact of chemotherapy is essential to develop current therapeutic approaches. Herein, we collected peripheral blood from 20 healthy donors and 50 patients with advanced NSCLC, before and after chemotherapy, followed by phenotypic analysis of lymphocyte subsets and assessment of the correlation between their post-chemotherapy levels and progression-free survival (PFS). Results showed that, before chemotherapy, the levels of CD8+ lymphocytes, PD-1+CD4+, Th2, and Th17 cells were elevated in patients' peripheral blood, in contrast to natural killer (NK) cells and Th1 cells. Besides, there was no remarkable difference in the frequency of PD-1+CD8+ cells between patients and healthy controls. After chemotherapy, the levels of CD8+ lymphocytes, NK, Th2, Th17, and Treg were declined, in contrast to the level of Th1 cells which was markedly increased. Importantly, chemotherapy had no impact on the frequencies of PD-1+CD8+ and PD-1+CD4+ cells. PFS was significantly better in patients with low percentage of PD-1+CD4+ T cells than those with high percentage. Patients with high content of Th1 cells showed longer PFS than those with low content. The low percentages of Th17 and Treg cells were correlated with longer PFS, even though the difference did not reach statistical significance. In conclusion, the imbalance of lymphocyte subsets is a hallmark of NSCLC. Furthermore, the high level of PD-1+CD4+ cells plays a crucial role in the progression of NSCLC and could be used as a prognostic marker; and the high level of Th1 could predict better clinical outcomes of chemotherapy.

Tumor-promoting properties of miR-8084 in breast cancer through enhancing proliferation, suppressing apoptosis and inducing epithelial-mesenchymal transition.

BACKGROUND: Breast cancer is one of the most frequent malignancies and the second leading cause of cancer-related mortality in women. MicroRNAs play a key role in breast cancer development and progression. microRNA(miR)-8084 has been observed an aberrant expression in breast cancer. However, the functions and regulatory axes of miR-8084, particularly in breast cancer, were not entirely clear. METHODS: miR-8084 expression in breast cancer were investigated in a GEO dataset by in silico analysis and in 42 paired tumor tissues by qPCR. The effects of deregulation of miR-8084 on breast cancer cell proliferation, migration and invasion in vitro and tumorigenicity in vivo were examined by colony-formation assay, wound healing assay, transwell assay and nude mouse subcutaneous tumor formation model. The target gene of miR-8084 were predicted by TargetScan and miRDB, and confirmed by luciferase reporter system. The roles of miR-8084 in the breast cancer cell proliferation, apoptosis and epithelial-mesenchymal transition (EMT) were investigated by MTS, FACS and associated-marker detection by western blot. RESULTS: miR-8084 is significantly up-regulated in both serum and malignant tissues from the source of breast cancer patients. miR-8084 promotes the proliferation of breast cancer cells by activating ERK1/2 and AKT. Meanwhile miR-8084 inhibits apoptosis by decreasing p53-BAX related pathway. miR-8084 also enhances migration and invasion by inducing EMT. Moreover, the tumor suppressor ING2 is a potential target of miR-8084, and miR-8084 regulatory axes contribute to pro-tumor effect, at least partially through regulating ING2. CONCLUSION: Our results strongly suggest that miR-8084 functions as an oncogene that promotes the development and progression of breast cancer, and miR-8084 is a potential new diagnostic marker and therapeutic target of breast cancer.

A microemulsion co-loaded with Schizandrin A-docetaxel enhances esophageal carcinoma treatment through overcoming multidrug resistance.

Multidrug resistance (MDR) is the major underlying cause of the low 5-year survival rate of esophageal carcinoma. In this study, we developed a novel microemulsion system (SD-ME) co-loaded with docetaxel (DTX) and Schizandrin A, a potent chemotherapeutic agent and a potential drug resistance modulator, respectively. In the physicochemical characterization studies, SD-ME displayed a well-defined spherical shape and size (56.62 ± 4.16 nm), a narrow polydispersity index (PDI, 0.132 ± 0.002), and a negative surface charge (-19.81 ± 3.11 mv). In the cellular uptake studies, SD-ME with a DTX concentration of 30 µg/mL exhibited a 3.9-fold enhancement of DTX internalization in DTX-resistant EC109 (EC109/DDR) cells in comparison to that observed for EC109 cells, and the mechanisms were associated with reducing P-gp expression and inhibiting P-gp ATPease. The half-maximal inhibitory concentrations (IC50) of DTX and SD-ME against EC109/DDR cells were 40.57 ± 0.39 and 3.59 ± 0.06 µg/mL, respectively. Likewise, the apoptotic rate of EC109/DDR treated with SD-ME increased up to 20-fold compared to that observed with free DTX. In anticancer efficacy studies in vivo, SD-ME markedly retarded the tumor growth of nude mice bearing EC109/DDR tumor xenografts compared with D-ME and free DTX throughout the duration of study. Consequently, mice treated with SD-ME had the highest survival rate (37.5%) during the observation period (70 days). In addition, there were no apparent side effects after the administration of SD-ME. Overall, our study provides evidence for SD-ME as an effective drug delivery system for enhanced MDR tumor treatment.

Electrochemical biosensor based on functional composite nanofibers for detection of K-ras gene via multiple signal amplification strategy.

An electrochemical biosensor based on functional composite nanofibers for hybridization detection of specific K-ras gene that is highly associated with colorectal cancer via multiple signal amplification strategy has been developed. The carboxylated multiwalled carbon nanotubes (MWCNTs) doped nylon 6 (PA6) composite nanofibers (MWCNTs-PA6) was prepared using electrospinning, which served as the nanosized backbone for thionine (TH) electropolymerization. The functional composite nanofibers [MWCNTs-PA6-PTH, where PTH is poly(thionine)] used as supporting scaffolds for single-stranded DNA1 (ssDNA1) immobilization can dramatically increase the amount of DNA attachment and the hybridization sensitivity. Through the hybridization reaction, a sandwich format of ssDNA1/K-ras gene/gold nanoparticle-labeled ssDNA2 (AuNPs-ssDNA2) was fabricated, and the AuNPs offered excellent electrochemical signal transduction. The signal amplification was further implemented by forming network-like thiocyanuric acid/gold nanoparticles (TA/AuNPs). A significant sensitivity enhancement was obtained; the detection limit was down to 30fM, and the discriminations were up to 54.3 and 51.9% between the K-ras gene and the one-base mismatched sequences including G/C and A/T mismatched bases, respectively. The amenability of this method to the analyses of K-ras gene from the SW480 colorectal cancer cell lysates was demonstrated. The results are basically consistent with those of the K-ras Kit (HRM: high-resolution melt). The method holds promise for the diagnosis and management of cancer.