Sprayable self-assembly multifunctional bioactive poly(ferulic acid) hydrogel for rapid MRSA infected wound repair.

The repair of methicillin-resistant staphylococcus aureus (MRSA) infected wounds remains a serious challenge. Development of multifunctional bioactive hydrogels has shown promising potential in treating MRSA wound. Ferulic acid has special bioactivities including antioxidant antiinflammation antibacterial capacities but limited in lack of engineering strategy for efficient treatment of MRSA infected wound. Herein, we developed a multifunctional bioactive poly(ferulic acid) copolymer (FPFA) for treating MRSA infected wound. FPFA could be self-assembled into hydrogel under body temperature and demonstrated the injectable, sprayable, self-healing, anti-inflammatory, antioxidant, and angiogenic activity. FPFA hydrogel also showed the good cytocompatibility, efficiently enhanced the endothelial cell migration, scavenged intracellular reactive oxygen species (ROS), inhibited the expression of inflammatory factors and enhanced the in vitro angiogenesis. The MRSA-infected wound model showed that FPFA could significantly inhibit the MRSA infection and excess inflammation, reinforce the angiogenesis, accelerate wound healing and skin tissue regeneration.

Efficient inactivation of the contamination with pathogenic microorganisms by a combination of water spray and plasma-activated air.

The global pandemic caused by SARS-CoV-2 has lasted two and a half years and the infections caused by the viral contamination are still occurring. Developing efficient disinfection technology is crucial for the current epidemic or infectious diseases caused by other pathogenic microorganisms. Gas plasma can efficiently inactivate different microorganisms, therefore, in this study, a combination of water spray and plasma-activated air was established for the disinfection of pathogenic microorganisms. The combined treatment efficiently inactivated the Omicron-pseudovirus through caused the nitration modification of the spike proteins and also the pathogenic bacteria. The combined treatment was improved with a funnel-shaped nozzle to form a temporary relatively sealed environment for the treatment of the contaminated area. The improved device could efficiently inactivate the Omicron-pseudovirus and bacteria on the surface of different materials including quartz, metal, leather, plastic, and cardboard and the particle size of the water spray did not affect the inactivation effects. This study supplied a disinfection strategy based on plasma-activated air for the inactivation of contaminated pathogenic microorganisms.

Oxygen vacancy mediated α-MoO3 bactericidal nanocatalyst in the dark: Surface structure dependent superoxide generation and antibacterial mechanisms.

Understanding bacteria inactivation mechanisms of nanomaterials on the surface molecular level is of prime importance for the development of antibacterial materials and their application in restraining the transmission of pathogenic microorganisms. This study prepared an oxygen vacancy-mediated bactericidal nanocatalyst α-MoO3 which exhibited excellent antibacterial activity against Escherichia coli and Staphylococcus aureus in the dark. By manipulating the surface structure of α-MoO3, the facile tuning of superoxide radical (•O2-) generation can be achieved, which was confirmed by electron paramagnetic resonance. •O2- disrupted bacterial membrane through attacking lipopolysaccharide (LPS) and phosphatidylethanolamine (PE). Intracellular reactive oxygen species (ROS) experiments confirm that oxidative stress induced by •O2- also played a vital role in bacterial inactivation, which might account for DNA damage verified by comet assays. The α-MoO3 with rich oxygen vacancies also exhibited good antibacterial efficiency (＞99.00 %) toward airborne microbes under dark conditions, indicating its potential to impede the transmission of pathogenic microbes.

Subanesthetic isoflurane abates ROS-activated MAPK/NF-κB signaling to repress ischemia-induced microglia inflammation and brain injury.

Isoflurane (ISO) elicits protective effects on ischemia-induced brain injury. We investigated whether sub-anesthetic (0.7%) ISO post-conditioning attenuates the inflammation and apoptosis in oxygen-glucose deprivation (OGD)-insulted co-cultures (microglia and neurons) in vitro and the brain injury of the middle cerebral arterial occlusion (MCAO) rat. We demonstrated that ISO augmented the viability of OGD-treated microglia and neurons. ISO reduced the expression and activation of COX2 and iNOS in OGD-challenged microglia. ISO repressed the production of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-8, and monocyte chemoattractant protein-1 in OGD-exposed microglia. ISO also decreased nucleosomal fragmentation and caspase-3 activity but increased mitochondrial membrane potential in OGD-stimulated microglia and neurons. Mechanistically, ISO suppressed OGD-induced microglial inflammation by blocking ROS-regulated p38 MAPK/NF-κB signaling pathway and hampered OGD-triggered microglial apoptosis in a ROS- or NO-dependent fashion. In vivo results with MCAO rats were partly consistent with the in vitro observation. These findings indicate that sub-anesthetic ISO post-conditioning abates the inflammation and apoptosis in OGD-stimulated rat microglia and the apoptosis of OGD-exposed neurons and the brain injuries of MCAO rats, suggesting it as a potentially effective therapeutic approach for ischemic brain damages.

Droplets Self-Born in the Dynamic Polymer for Generating Functional Coatings.

Droplet-embedded structures are useful in functionalizing polymer composites but difficult to prepare. Herein, we report a facile self-born method for creating droplets in supramolecular gels to mediate the material's functions. This method is based on the amplification of the defects of polymer matrices generated in curing by swelling-driving reconfiguration of supramolecular polymer networks. The system of poly(urea-co-polydimethylsiloxane) that can cross-link via hydrogen-bond interaction is used to demonstrate our concept. The elastomer matrices are prepared via a casting method and exhibit a heterogeneous structure with both strong- and weak-cross-linking domains. When these materials are swelled in solvents, solvent molecules concentrate in the weak-cross-linking domains to nucleate. With the reconfiguration of the matrices, the nuclei grow into pure droplets, leading to the formation of droplet-embedded structures. This method is applicable to different material systems. We also show that obtained coatings with such droplet-embedded structures exhibit various interesting properties including self-replenishment of the surface liquid, mechanoresponsiveness, and self-healing ability. Moreover, after the droplets are consumed, this method can be used to regenerate the droplet-embedded structure for refunctionalizing the materials. Therefore, we envision its applications in preparation of many useful polymer composites.

CRIF1 overexpression facilitates tumor growth and metastasis through inducing ROS/NFκB pathway in hepatocellular carcinoma.

CR6-interacting factor 1 (Crif1) is a mitochondrial protein which is required for the assembly of oxidative phosphorylation (OXPHOS) complexes. Our bioinformatics analysis based on Cancer Genome Atlas (TCGA) database revealed an aberrant overexpression of CRIF1 in hepatocellular carcinoma (HCC). However, the clinical significance and biological functions of CRIF1 are still unclear in this malignancy. Here, we report that CRIF1 is frequently overexpressed in HCC cells mainly due to the downregulation of miR-497-5p, which is associated with poor prognosis of patients with HCC. CRIF1-promoted HCC growth and metastasis by suppressing cell apoptosis and inducing cell cycle progression and epithelial to mesenchymal transition (EMT). Mechanistically, increased mitochondrial ROS production and consequently activation of the NFκB signaling pathway was found to be involved in the promotion of growth and metastasis by CRIF1 in HCC cells. In summary, CRIF1 plays an oncogenic role in HCC progression through activating ROS/NFKB pathway, implying CRIF1 as a potential prognostic factor and therapeutic target in HCC.

miRNA-mediated macrophage behaviors responding to matrix stiffness and ox-LDL.

Atherosclerosis is one of the leading causes of morbidity and mortality, mainly due to the immune response triggered by the recruitment of monocytes/macrophages in the artery wall. Accumulating evidence have shown that matrix stiffness and oxidized low-density lipoproteins (ox-LDL) play important roles in atherosclerosis through modulating cellular behaviors. However, whether there is a synergistic effect for ox-LDL and matrix stiffness on macrophages behavior has not been explored yet. In this study, we developed a model system to investigate the synergistic role of ox-LDL and matrix stiffness on macrophage behaviors, such as migration, inflammatory and apoptosis. We found that there was a matrix stiffness-dependent behavior of monocyte-derived macrophages stimulated with ox-LDL. What's more, macrophages were more sensitive to ox-LDL on the stiff matrices compared to cells cultured on the soft matrices. Through next-generation sequencing, we identified miRNAs in response to matrix stiffness and ox-LDL and predicted pathways that showed the capability of miRNAs in directing macrophages fates. Our study provides a novel understanding of the important synergistic role of ox-LDL and matrix stiffness in modulating macrophages behaviors, especially through miRNAs signaling pathways, which could be potential key regulators in atherosclerosis and immune-targeted therapies.

Prognostic Significance and Diagnostic Value of Overexpressed lncRNA PVT1 in Colorectal Cancer.

BACKGROUND: The aim of this study is to investigate the expression of lncRNA PVT1 in CRC tissue compared to adjacent normal tissues, and reveal the association between lncRNA PVT1 expression level and the clinicopathological characteristics of patients with CRC. METHODS: We detected the lncRNA PVT1 relative expression of cancerous tissues in 130 patients with CRC by using real-time quantitative polymerase chain reaction. At the same time, we collected the clinicopathological and prognostic information. RESULTS: IncRNA PVT1 was overexpressed in CRC tissues compared to paired-adjacent normal tissues and the high expression rate was 72.31%. High expression of lncRNA PVT1 predicts a later tumor stage (p = 0.001), poorer tissue differentiation (p = 0.019), and higher plasma CEA level (p = 0.043). Additionally, the lncRNA PVT1 expression was closely related to lymph node metastasis (N1/N2 vs. N0) and distant metastasis (M1 vs. M0) in CRC patients (p = 0.002; p = 0.003), but not to tumor T classification (p = 0.314). The result of prognostic analysis indicated that the 1-year and 3-year DFS of the lncRNA PVT1 low and high expression patients were 93.8% and 81.1%, 69.3% and 44.7%, respectively. The median DFS was 44 months in low expression group and 26 months in high expression group, with statistical significance (p = 0.021). COX multivariate analysis showed that TNM staging (III/IV vs. I/II: HR = 6.342, 95% CI: 2.994 - 13.433, p < 0.001) and the lncRNA PVT1 expression (high expression vs. low expression: HR = 3.744, 95% CI: 1.493 - 9.392, p = 0.005) was closely related to DFS in CRC patients. As with tumor TNM staging, lncRNA PVT1 expression was also an independent prognostic predictor of DFS. The proportion of lncRNA PVT1 high expression (fold change ≥ 1.725) was higher than that of elevated CEA ( > 5 ng/mL) in different CRC stages, especially, there was a significant difference in stage I patients (X2 = 41.717, p < 0.0001). CONCLUSIONS: The lncRNA PVT1 was over-expressed in CRC tissues, which indicated a poor prognosis. The lncRNA PVT1 expression is far higher than the plasma CEA level in the early stage patients, which has the potential diagnostic value for early stage CRC.

Oncogenic USP22 supports gastric cancer growth and metastasis by activating c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling.

In this study, we investigated the role of ubiquitin-specific protease 22 (USP22) in the growth and progression of gastric cancer (GC). USP22 mRNA and protein levels were significantly higher in GC tissue samples and GC cell lines than in adjacent noncancerous tissue samples and a normal gastric mucosal epithelial cell line (GES1), respectively. USP22 knockdown significantly decreased in vitro survival, proliferation, migration, and invasiveness of GC cells compared with the controls. Western blot analysis of control and USP22-silenced GC cells showed that USP22 modulates the c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling pathways. Subcutanenous injection of USP22-silenced GC cells into SCID mice generated significantly smaller xenograft tumors than did control cells. Moreover, USP22-silenced GC cells showed less lung metastasis than the controls following tail vein injection in SCID mice. In addition, high USP22 expression correlated positively with tumor size, advanced stage and metastasis, and correlated negatively with tumor differentiation and prognosis in GC patients. These results show that USP22 regulates growth and progression of GC via the c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling pathways.

Retraction Note: Nuclear factor of activated T cells 5 maintained by Hotair suppression of miR-568 upregulates S100 calcium binding protein A4 to promote breast cancer metastasis.

The authors are retracting this article [1] after an investigation by the Ethics Committee of the Fourth Military Medical University (Xi'an, Shaanxi, China) of the following concerns that had been raised with respect to two of the figures.

Increased Expression of PCNA-AS1 in Colorectal Cancer and its Clinical Association.

BACKGROUND: The aim is to study the expression of PCNA-AS1 in colorectal cancer (CRC) tissue and paired-adjacent normal tissue and the relationship between its expression level and clinical pathological features. METHODS: Using real-time qPCR, PCNA-AS1 expression levels were detected in 114 cases to establish the relationship between its expression and clinicopathologic features. Moreover, the expressions of PCNA-AS1 were investigated in CRC and normal colonic epithelial cell lines. RESULTS: PCNA-AS1 was upregulated in CRC patients. The difference was statistically significant (p < 0.001). The expression level was significantly correlated with the tumor invasion and TNM stage. The area under the receiver operating characteristic curve, sensitivity, and specificity were 0.824, 0.632, and 0.860, respectively. Moreover, PCNA-AS1 was up-regulated in CRC cell lines. CONCLUSIONS: PCNA-AS1 may function as a potential tumor biomarker for diagnosing CRC.

Long Noncoding RNA PVT1 as a Potent Predictor of Prognosis in Cancers: a Meta-Analysis.

BACKGROUND: Plasmacytoma variant translocation 1 (PVT1), an oncogenic long noncoding RNA located in a recognized cancer-risk gene region-8q24, is significantly overexpressed in various cancers. Many studies have found that high expression of PVT1 was correlated with poor prognosis. METHODS: This meta-analysis was performed by searching electronic databases Pubmed, Web of Science, Chinese National Knowledge Infrastructure, WanFang, and ChongQing VIP for eligible papers on the prognostic impact and clinicopathological characteristics of PVT1 expression in cancer from inception to January 31, 2017. The hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CI) were computed to estimate the pooled effect of PVT1 on prognosis of cancers using Stata 12.0 version software. RESULTS: Thirteen studies were finally included in this review with a total of 1559 patients. The pooled result indicated that overexpressed PVT1 predicts a poorer prognosis of cancerous patients for overall survival (HR = 1.91, 95% CI: 1.61 - 2.26, p < 0.001) and disease-free survival (HR = 1.90, 95% CI: 1.46 - 2.48, p < 0.001) or recurrencefree survival (HR = 1.77, 95% CI: 1.24 - 2.52, p = 0.002) or progression-free survival (HR = 2.84, 95% CI: 1.67 - 4.82, p < 0.001). High expression of PVT1 was closely associated with tumor-node-metastasis (TNM) stage (III/IV vs. I/II: OR = 3.19, 95% CI: 2.43 - 4.18, p < 0.001), and the significant correlation between PVT1 expression and TNM stage is found in T classification (T3/4 vs. T1/2: OR = 6.48, 95% CI: 2.93 - 14.31, p < 0.001) and lymph node metastasis (present vs. absent: OR = 2.56, 95% CI:1.36 - 4.80, p = 0.003), but not in distant metastasis of patients with cancers (yes vs. no: OR = 2.50, 95% CI: 0.72 - 8.66, p = 0.15). Furthermore, the cancerous patients with high PVT1 expression had a worse histological differentiation than those with low PVT1 expression (undifferentiated/poorly vs. moderately/well: OR = 1.48, 95% CI: 1.02 - 2.14, p = 0.039). CONCLUSIONS: PVT1 could serve as a potent predicator of prognosis in different types of cancers.

Epithelial HO-1/STAT3 affords the protection of subanesthetic isoflurane against zymosan-induced lung injury in mice.

Epithelial dysfunction is a key characteristic of acute lung injury (ALI). Isoflurane (ISO) confers lung protection via anti-inflammatory and anti-apoptotic properties. However, the specific role and potential mechanisms of subanesthetic ISO in lung epithelium protection during zymosan-induced ALI remain unclear. In this study, zymosan increased the expression and activity of beneficial heme oxygenase-1 (HO-1) and signal transducers and activators of transcription 3 (STAT3) in the lung and isolated type II alveolar epithelial cells (AECs-II) from wild-type (WT) mice, which was further enhanced by ISO treatment. ISO reduced the mortality, lung edema, histological changes and pulmonary cell apoptosis, and simultaneously decreased total cells, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels in bronchoalveolar lavage fluid in the zymosan-stimulated WT mice but not in HO-1-deficient mice. Moreover, ISO abated zymosan-augmented lactate dehydrogenase activity, TNF-α and IL-1ß production, and apoptosis in WT AECs-II but not in HO-1- or STAT3-silenced cells. Mechanisticly, the epithelial protective effects of ISO on zymosan insult in vivo and in vitro were mediated by a positive feedback loop comprising STAT3 and HO-1. Pro-survival and anti-apoptosis by ISO was highly reliant on activated STAT3, involving in downstream Akt activation and reduced ratio of pro-apoptotic/anti-apoptotic molecules. Overall, HO-1/STAT3 signaling is in favor of lung epithelial protection of ISO in zymosan-challenged mice, suggesting ISO as a valuable therapeutic agent for ALI.

Swimming attenuates inflammation, oxidative stress, and apoptosis in a rat model of dextran sulfate sodium-induced chronic colitis.

Increasing evidence suggests that regular physical exercise suppresses chronic inflammation. However, the potential inhibitory effects of swimming on dextran sulfate sodium (DSS)-induced chronic colitis, and its underlying mechanisms, remain unclear. In this study, rats were orally administered DSS to induce chronic colitis, and subsequently treated with or without swimming exercise. A 7-week swimming program (1 or 1.5 hours per day, 5 days per week) ameliorated DSS-caused colon shortening, colon barrier disruption, spleen enlargement, serum LDH release, and reduction of body weight gain. Swimming for 1.5 hours per day afforded greater protection than 1 hour per day. Swimming ameliorated DSS-induced decrease in crypt depth, and increases in myeloperoxidase activity, infiltration of Ly6G+ neutrophils and TNF-α- and IFN-γ-expressing CD3+ T cells, as well as fecal calprotectin and lactoferrin. Swimming inhibited pro-inflammatory cytokine and chemokine production and decreased the protein expression of phosphorylated nuclear factor-κB p65 and cyclooxygenase 2, whereas it elevated interleukin-10 levels. Swimming impeded the generation of reactive oxygen species, malondialdehyde, and nitric oxide; however, it boosted glutathione levels, total antioxidant capacity, and superoxide dismutase and glutathione peroxidase activities. Additionally, swimming decreased caspase-3 activity and expression of apoptosis-inducing factor, cytochrome c, Bax, and cleaved-caspase-3, but increased Bcl-2 levels. Overall, these results suggest that swimming exerts beneficial effects on DSS-induced chronic colitis by modulating inflammation, oxidative stress, and apoptosis.

Identification and verification of PRDX1 as an inflammation marker for colorectal cancer progression.

Chronic inflammation contributes to high risk of colorectal cancer (CRC) development. Thus, discovering inflammation biomarkers for monitoring of CRC progression is necessary. In this study, we performed isobaric tags for relative and absolute quantitation-based proteomic assay on CRC tissues and paired normal mucosal tissues to identify key components in CRC pathogenesis. A total of 115 altered protein expressions were found with over twofold difference as compared with normal controls, which were associated with various molecular functions and biological processes. Here, we found that peroxiredoxin 1 (PRDX1) expression was higher in CRC tissues than that of matched controls and was determined as a tumor biomarker by receiver operating characteristic curve. PRDX1 expression was significantly upregulated in NCM460 cells challenged by H2O2 in a dose-dependent manner. PRDX1 depletion in SW480 cells enhanced reactive oxygen species (ROS), NO, and ONOO(-) production and increased the mRNA and protein expressions of pro-inflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6] and chemokines (IL-8 and CXCL1), and partly activated nuclear factor-κB p65. Overall, our findings provide data on global alteration in the proteome of CRC tissues and reveal the potential of PRDX1 as an inflammation marker in CRC development, suggesting a novel therapy against inflammation-associated CRC.

Subanesthetic isoflurane relieves zymosan-induced neutrophil inflammatory response by targeting NMDA glutamate receptor and Toll-like receptor 2 signaling.

Neutrophil release of NO/ONOO- induces endothelial cell barrier dysfunction in inflammatory acute lung injury (ALI). Previous studies using zymosan-triggered inflammation and ALI model revealed that zymosan promotes inducible NO synthase (iNOS) expression in neutrophils, and that isoflurane inhibits zymosan-induced oxidative stress and iNOS biosynthesis. However, the underlying mechanisms remain largely unknown. We found here that in zymosan-primed neutrophils, iNOS is transcriptionally activated by NF-κB, whose nuclear translocation is triggered by excessive reactive oxygen species (ROS) and consequently activated p38 MAPK. ROS production is attributed to zymosan-initiated Toll-like receptor 2 (TLR2) signaling, in which the adaptor MyD88 recruits and activates c-Src, and c-Src activates NADPH oxidase to generate ROS. Subanesthetic isoflurane counteracts the aforementioned zymosan-induced signaling by targeting N-methyl-D-aspartic acid (NMDA) glutamate receptor and thereby suppressing calcium influx and c-Src activation. Whereas iNOS accelerates NO/ONOO- production in neutrophils which eventually promote protein leak from pulmonary microvascular endothelial cells (PMVEC), isoflurane reduced NO/ONOO- release from zymosan-treated neutrophils, and thus relieves trans-PMVEC protein leak. This study provides novel insights into the roles of neutrophils and the underlying mechanisms in zymosan-induced ALI, and has implications for the therapeutic potential of subanesthetic isoflurane in attenuating inflammatory responses causing lung endothelial cell damage.

Targeting ubiquitin-specific protease 22 suppresses growth and metastasis of anaplastic thyroid carcinoma.

Ubiquitin-specific protease 22 (USP22) aberrance has been implicated in several malignancies; however, whether USP22 plays a role in anaplastic thyroid carcinoma (ATC) remains unclear. Here, we report that USP22 expression is highly elevated in ATC tissues, which positively correlated with tumor size, extracapsular invasion, clinical stages, and poor prognosis of ATC patients. In vitro assays showed that USP22 depletion suppressed ATC cell survival and proliferation by decreasing Rb phosphorylation and cyclin D2, inactivating Akt, and simultaneously upregulating Rb; USP22 silencing restrained cell migration and invasion by inhibiting epithelial-mesenchymal transition; USP22 knockdown promoted mitochondrion- mediated and caspase-dependent apoptosis by upregulating Bax and Bid and promoting caspase-3 activation. Consistent with in vitro findings, downregulation of USP22 in ATC cells impeded tumor growth and lung metastasis in vivo. These results raise the applicability for USP22 as a useful predictor of ATC prognosis and a potential therapeutic target for ATC.

Integrative bioinformatics and proteomics-based discovery of an eEF2K inhibitor (cefatrizine) with ER stress modulation in breast cancer cells.

Eukaryotic elongation factor-2 kinase (eEF2K), a unique calcium/calmodulin-dependent protein kinase, is well known to regulate apoptosis, autophagy and ER stress in many types of human cancers. Therefore, eEF2K would be regarded as a promising therapeutic target; however, the eEF2K-regulated mechanism and its targeted inhibitor still remain to be discovered in cancer. Herein, we constructed a protein-protein interaction (PPI) network of eEF2K and achieved an eEF2K-regulated ER stress subnetwork by bioinformatics prediction. Then, we found that the differential protein expressions involved in ER stress in the context of si-eEF2K-treated MCF-7 and MDA-MB-436 cells by iTRAQ-based analyses, respectively. Integrated into these aforementioned results, we constructed a core eEF2K-regulated ER stress subnetwork in breast cancer cells. Subsequently, we screened a series of candidate compounds targeting eEF2K and discovered a novel eEF2K inhibitor (cefatrizine) with an anti-proliferative activity toward breast cancer cells. Moreover, we found that cefatrizine induced ER stress in both MCF-7 and MDA-MB-436 cells. Interestingly, we demonstrated that the mechanism of cefatrizine-induced ER stress was in good agreement with our bioinformatics and proteomics-based results. In conclusion, these results demonstrate that a novel eEF2K inhibitor (cefatrizine) induces ER stress in breast cancer cells by integrating bioinformatics prediction, proteomics analyses and experimental validation, which would provide a clue for exploring more mechanisms of eEF2K and its targeted inhibitors in cancer therapy.

MiRNA-101 inhibits breast cancer growth and metastasis by targeting CX chemokine receptor 7.

Whereas miR-101 is involved in the development and progression of breast cancer, the underlying molecular mechanisms remain to be elucidated. Here, we report that miR-101 expression is inversely correlated with the clinical stage, lymph node metastasis and prognosis in breast cancers. Introduction of miR-101 inhibited breast cancer cell proliferation and invasion in vitro and suppressed tumor growth and lung metastasis of in vivo. CX chemokine receptor 7 (CXCR7) is a direct target of miR-101, positively correlating with the histological grade and the incidence of lymph node metastasis in breast cancer patients. The effects of miR-101 were mimicked and counteracted by CXCR7 depletion and overexpression, respectively. STAT3 signaling downstream of CXCR7 is involved in miR-101 regulation of breast cancer cell behaviors. These findings have implications for the potential application of miR-101 in breast cancer treatment.

MicroRNA library-based functional screening identified miR-137 as a suppresser of gastric cancer cell proliferation.

PURPOSES: Uncontrolled proliferation is a key characteristic of gastric carcinogenesis and the precise mechanisms underlying the altered proliferation behaviors of GC cells have not been clearly elucidated. miRNAs has been suggested to play a crucial role in the pathogenesis and development of various cancers. In the present study, we employed an impedance-based real-time cell electronic sensing (RT-CES) system to detect the effects of ectopically expressed miRNAs on GC cell proliferation. METHODS: miRNA mimics were transfected into gastric cancer cell line SGC7901 and the effect of individual miRNA on the proliferation rate of the cells was measured by the RT-CES system. The screening results were validated with qRT-PCR and miR-137 was selected for further research. The effects of ectopically expressed miR-137 on GC cell growth and cell cycle progress were measured using MTT assay and flow cytometry. The target gene of miR-137 was predicted using different bioinformatics tools and the direct interaction between miR-137 and the 3'-UTR was confirmed with a luciferase reporter assay. The in vivo effect of miR-137 on GC cell proliferation was examined with a tumor-bearing nude mouse model. The correlation between miR-137 expression and patients' prognosis was explored in a cohort of 38 patients. Prognosis was explored in a cohort of 38 patients. RESULTS: Ectopic expression of miR-137 was sufficient to inhibit GC cell proliferation both in vitro and in vivo. Bioinformatics prediction and luciferase reporter assay revealed CDK6 as a target gene through which miR-137 exerted an inhibitory function. Moreover, miR-137 expression positively correlated with better prognosis. CONCLUSION: Our data indicated an important regulatory role of miR-137 in GC cell proliferation and that it may be explored as a prognostic marker for GC.