Identification of 10 differentially expressed and cuproptosis-related genes in immune infiltration and prognosis of thyroid carcinoma.

The association between the cuproptosis-related genes and the immune infiltration and their prognostic value in thyroid carcinoma is still unexplored. Bioinformatics analyses were performed with data obtained from the TCGA dataset. The aberrantly expressed genes were selected. KEGG and GO analyses were conducted to explore the enriched pathways of the up-regulated or down-regulated genes in thyroid carcinoma. Totally 1495 genes were differentially expressed (691 up-regulated, 804 down-regulated) in thyroid carcinoma (p<0.05). The 10 cuproptosis-related RNAs (DLD, LIAS, LIPT1, FDX1, DLAT, MTF1, PDHA1, CDKN2A, GLS and PDHB) were also demonstrated to be aberrantly expressed in thyroid carcinoma patients tissues. FDX1 expression was correlated with the overall survival in thyroid carcinoma patients (HR=0.4995, 95% CI: 0.2688-0.9285, p=0.0282). Further multivariate cox regression analysis revealed that DLD (HR=24.8869, 95% CI: 4.48772-138.01181, p=0.00024), and LIAS (HR=7.74092, 95% CI: 1.12194-53.40898, p=0.03783) were associated with the survival of thyroid carcinoma patients. The immune infiltration analysis demonstrated that significant correlation between the 10 cuproptosis-related genes and immune infiltration in thyroid carcinoma (p<0.01). We presented the expression profiles of dysregulated genes in thyroid carcinoma. The findings of our study highlighted the potential of cuproptosis-related genes as prognostic biomarkers for thyroid carcinoma.

Effect of initial water content on the dewatering performance of freeze-thaw preconditioned landfill sludge.

Freeze-thawing (F/T) is an effective method of sludge dewatering preconditioning and has been studied in many studies. However, previous studies have taken landfill sludge from different regions, filled for different length of time or at different depth, resulting in large differences in initial water content and different treatment effects. Therefore, the effect of initial water content on the dewatering characteristics of F/T preconditioned landfill sludge has been investigated. The sludge with different initial water contents was firstly preconditioned by one F/T cycle. Then the F/T sludge was vacuum filtered and compared with the dewatering performance of FeCl3 preconditioned sludge with the same water content. Finally, the mechanism of the initial water content on the effect of F/T preconditioning was analyzed by the change of sludge internal composition. The results show that the higher the initial water content of the sludge, the greater the improvement of its dewatering performance after F/T preconditioning. The specific resistance and water content after filtration of sludge after F/T conditioning decreased greatly with the increase of the initial water content, reaching their respective minimum values of 13.3 × 1012 m/kg and 58.3% at 85% and 87.5%. These values are lower than the optimal values observed for the sludge conditioned by FeCl3. With the rise in initial water content, the driving force at the ice-water interface gains strength. Small particles aggregate into larger flocs, forming stable drainage channels that enhance the dewatering performance of sludge. Once the initial water content surpasses 85%, the squeezing force exerted by ice crystals amplifies the degree of cracking in sludge particles, releasing bound water and further decreasing the water content of sludge.

Characteristics of fundus autofluorescence imaging at 795 nm and its correlations with postoperative outcomes for idiopathic macular hole.

BACKGROUND: Vitrectomy combined with internal limiting membrane (ILM) peeling or ILM inverted flap greatly improves hole closure and vision prognosis for idiopathic macular holes (IMH). The application of indocyanine green (ICG) in MH surgery increases the visibility of ILM and the safety of surgery. However, the area of ILM peeling and the state of the flap and a closed hole has not been well observed. AIM: Fundus autofluorescence at 7935nm can show the range of ILM peeling and the state of the hole site and ILM flap by monitoring residual ICG postoperatively. However, the characteristics of fundus autofluorescence especially the site of the closed hole, and its relationship with vision prognosis have not been explored. The aim of this project was to find the autofluorescence features of the closed hole and their relation with vision. OBJECTIVE: To investigate the characteristics of fundus autofluorescence imaging after ICG-assisted vitrectomy for IMH and to evaluate the correlations of fluorescence patterns at the MH site with visual acuity and macular anatomic outcomes. METHODS: We retrospectively evaluated 33 IMH patients (33 eyes) who underwent a 25G pars plana vitrectomy (follow-up, 6-14.5 months). ICG staining (2.5 mg/mL) was either used to remove the internal limiting membrane (ILM) or the inverted ILM flap was overlaid on the hole. After surgery, fluorescence imaging of the fundus was obtained using a scanning laser ophthalmoscope at 795 nm. RESULTS: On fluorescence imaging, the area of ILM peeling in all eyes showed hypofluorescence with no changes over time. The inverted ILM flap (performed in 18 eyes) was positioned on the inferior retina and exhibited early mild hyperfluorescence with blurred edges. This was gradually enhanced up to 3-6 months postoperatively and was then attenuated. MHs showed two distinct patterns on optical coherence tomography: granular (21 eyes) and patchy hyperfluorescence (12 eyes). Best-corrected visual acuity improved postoperatively in all cases (p<0.001, Z=-4.744). VA was worse in the patchy (vs. granular) hyperfluorescence cases (p=0.011, Z=-2.548). CONCLUSION: The status of the ILM peeling area, ILM flap, and closed MH can be clearly observed using autofluorescence imaging at 795 nm. Fluorescence may be due to ICG staining of the ILM and accumulation in retinal pigment epithelium cells during ICG-assisted surgery. Granular hyperfluorescence at the MH site may indicate good anatomic and visual prognoses.

Clinical Observation of Anatomical and Visual Outcomes of Macular Hole after Inverted Internal Limiting Membrane Flap in Patients with Idiopathic Macular.

Objective: To investigate anatomical and visual outcomes of macular hole (MH) after inverted internal limiting membrane (ILM) flap technique for idiopathic macular hole (IMH). Methods: A total of 13 IMH cases diagnosed in Shanxi Eye Hospital between January 2015 and June 2016 were included in the study. All patients underwent vitrectomy combined with indocyanine green-assisted inverted ILM flap technique. The MH closure rate, best-corrected visual acuity (BCVA), changes of ellipsoid zone (EZ), and external limiting membrane (ELM) were examined before operation and one, three, and six months after operation. Furthermore, 488 nm fundus autofluorescence (FAF) and spectral domain optical coherence tomography (SD-OCT) were used to observe the dynamic changes in function of macular area after surgery. Results: One month after the surgery, the MH closure rate was 100% and the visual acuity (VA) was stable, with no recurrence. Additionally, the average logMAR BCVA before operation was 1.208 ± 0.158, and this value became 0.877 ± 0.105 one month after the operation, showing a significant decrease. Three months after surgery, the average logMAR BCVA was 0.792 ± 0.103, which was significantly lower than the level one month after the surgery but much higher than that six months after surgery (0.708 ± 0.131). Besides, the diameter of the EZ defect of the postoperative one month, three months, and six months was (1377.46 ± 198.65) µm, (964.62 ± 336.26) µm, and (817.08 ± 442.99) µm, respectively. In postoperative one month, three months, and six months, the diameter of the ELM defect diameter was (969.62 ± 189.92) µm, (649.92 ± 413.15) µm, and (557.62 ± 412.50) µm, respectively. The diameter of both EZ and ELM defects was significantly reduced with the passage of time after surgery. Conclusion: Inverted ILM flap technique can reconstruct macular anatomical structure and improve VA. This technique is effective for the treatment of IMH with large MH minimum diameter and base diameter.

The role amenities play in spatial sorting of migrants and their impact on welfare: Evidence from China.

From 2005 to 2015, China's high-skilled labor was increasingly concentrated in cities with high wages and high rents, while a narrowing of the wage gap between high- and low-skilled labor showed an opposite trend to an increase in geographic sorting. In this research, I estimated a spatial equilibrium structural model to identify the causes of this phenomenon and its impact on welfare. Changes in local labor demand essentially led to an increase in skill sorting, and changes in urban amenities further contributed to this trend. An agglomeration of high-skilled labor raised local productivity, increased wages for all workers, reduced the real wage gap, and widened the welfare gap between workers with different skills. In contrast to the welfare effects of changes in the wage gap driven by exogenous productivity changes, changes in urban wages, rents, and amenities increased welfare inequality between high- and low-skilled workers, but this is mainly because the utility of low-skilled workers from urban amenities is constrained by migration costs; if migration costs caused by China's household registration policy were eliminated, changes in urban wages, rents, and amenities would reduce welfare inequality between high- and low-skilled workers to a greater extent than a reduction in the real wage gap between these two groups.

Anti-clogging mechanism of freeze-thaw combined with step vacuum preloading in treating landfill sludge.

Globally, landfill sludge (LS) has accumulated in large quantities, and its reduction and dewatering are urgently needed. To address pollution problems and clogging of drainage boards caused by chemical conditioning combined with traditional vacuum preloading (TVP), a freeze-thaw combined with step vacuum preloading (F/T-SVP) method is proposed. A comparative experimental study was carried out between TVP and SVP to explore the anti-clogging mechanism of F/T-SVP in treating LS. As a result, the water discharge for the original sludge (OS) is 1840 ml, the water discharge for TVP is 8830 ml and for SVP is 10,010 ml; The total settlement of SVP is 16% higher than that of TVP; TVP has a volume reduction ratio of 57.6%, while SVP has 66.8%; the OS's water content was 86%, which was reduced to 57.6% by F/T-SVP; The center of the drainage board of TVP is seriously clogged, while the particles of SVP are evenly distributed; The tendency for small particles to undergo transport is relatively low at the beginning of SVP, which can effectively reduce clogging; TVP mainly focuses on the compression of large pores into small pores, and SVP mainly focuses on the compression of large into small pores and micropores. In SVP, there is more consolidation and a more compact structure. When F/T-SVP is used to treat LS, the pores are gradually penetrated, effectively avoiding the generation of clogging and improving LS's drainage and consolidation.

Dehydration effect of freeze-thaw on sludge: Temperature spatio-temporal distribution and multi-scale evaluation.

The freeze-thaw vacuum method for conditioning pretreated sludge has been proved that it not only has greater dewatering efficiency but also is more ecologically friendly. In this paper, the experiment is improved to address shortcomings in previous freeze-thaw vacuum approach for sludge treatment. The spatio-temporal distribution relationship of distance-time-temperature is developed and divided into two stages by numerically fitting the temperature change of freezing tubes in the sludge. It is expected to guide the time control of large-scale frozen sludge in practical engineering applications to achieve optimal dewatering treatment. Furthermore, the performance of dehydration after the model test is evaluated on multi-scale: settlement and mechanical properties (macroscopic perspective), mean particle size (mesoscopic perspective), and SEM microstructure (microscopic perspective). The results reveal that the improved sludge treatment method of alternating freeze-thaw vacuum procedures, using both prefabricated horizontal drains (PHDs) and prefabricated vertical drains (PVDs), substantially benefits the sludge dewatering and reduction. This method results in an unparalleled volume reduction of 63.51% and a water content reduction to 58.54%. Moreover, in-situ vane shearing strength of the sludge obtained from the improved test meets the strength requirement for the landfill final cover soil, demonstrating that the method is superior in improving mechanical properties.

Freeze-thaw vacuum treatment of landfill sludge: Mechanism of uneven frost heaving and dewatering performance.

The method of freeze-thaw combined with vacuum pretreatment for landfill sludge (LS) has attracted extensive attention. However, most of the existing approaches are based on small-scale laboratory testing, and further testing studies must be performed to realize in situ treatment. To enhance the practicality of such approaches, the range of temperature effects on LS was analysed after field freeze-thaw model testing. After the freeze-thaw model test, samples were transported to the laboratory for unidirectional oedometer tests, and the remaining samples were retained in the field to continue vacuum model testing for exploring the differences in the consolidation and drainage effect of the LS. Results show that temperature changes during freeze-thaw process affect the distribution of sludge and water in the model boxes, resulting in frost heave and the appearance of "extrusion rings". In addition, the coefficient of consolidation obtained from the unidirectional oedometer test shows that the consolidation coefficient is generally larger near the freezing tubes at a lower temperature. The settlement determined from the field vacuum preloading test shows that the subsequent vacuum consolidation settlement is larger at the position with a lower elevation of the frozen sludge surface. The comparison indicates that the consolidation and drainage effect in the field is not as significant as that in the laboratory. The findings can provide reference to optimize the field conditions during the in situ engineering practice of sludge treatment.

Effect of intravitreal conbercept injection on VEGF-A and -B levels in the aqueous and vitreous humor of patients with proliferative diabetic retinopathy.

The present study aimed to investigate the mechanisms of anti-VEGF treatment prior to eye surgery to reduce intraoperative bleeding. A total of 30 patients with proliferative vitreoretinopathy after clinical diagnosis were enrolled in the present study as the surgical group. Furthermore, 30 patients underwent intravitreal injection of the anti-VEGF drug conbercept and were considered the drug pretreatment group. The aqueous and vitreous humors from the eyes of patients in the surgical group were drawn during pars plana vitrectomy surgery. The aqueous humor in the eyes of patients in the drug pretreatment group was drawn prior to conbercept treatment and seven days after conbercept treatment immediately prior to surgery. The vitreous humor in this group was only taken during surgery. Furthermore, ELISA was used to detect the levels of VEGF-A and -B in the aqueous and vitreous humors. Semi-quantitative determination of VEGF-A and VEGF-B levels in fibrovascular proliferative membranes was performed using immunohistochemical staining. The results indicated that in the drug group, the levels of VEGF-A in the aqueous humor of patients prior to and after conbercept injection were 197.66±48.00 and 3.39±2.54 pg/ml, respectively. The levels of VEGF-A in the vitreous humor of patients in the surgical and drug groups were 267.53±179.60 and 21.43±5.81 pg/ml after injection, respectively. The levels of VEGF-B in the aqueous humor of patients prior to and after conbercept injection were 13.66±3.30 (before injection) and 2.17±0.94 pg/ml (after injection), respectively. The levels of VEGF-B in the vitreous humor of patients in the surgical and drug groups were 127.36±16.72 and 18.56±9.82 pg/ml after injection, respectively (P<0.05). Furthermore, in the drug group, the surgery time, bleeding and capillary formation were significantly reduced compared with those in the surgical group. Taken together, these results suggested that the levels of VEGF-A and -B decreased significantly in the aqueous humor of patients with PDR after conbercept injection. Furthermore, the levels of VEGF-A and -B in the vitreous humor of patients dropped significantly in the drug group compared with those in the surgical group. These results provide theoretical clinical support for the preoperative application of conbercept for patients with PDR.

Experimental study on treating landfill sludge by preconditioning combined with vacuum preloading: Effects of freeze-thaw and FeCl3 preconditioning.

The deep dewatering of landfill sludge (LS) mainly uses the methods of chemical preconditioning and mechanical dewatering, which is easy to cause environmental pollution and is not conducive to the subsequent recycling treatment of sludge. To find a more environment-friendly and efficient method for LS's deep dewatering and volume reduction, an in-situ sludge treatment method combining freeze-thaw (F/T) preconditioning and vacuum preloading was proposed. Firstly, the F/T test of LS was carried out to explore the optimum freezing temperature. FeCl3, the most widely used agent, was selected as the chemical preconditioning. Then carry out vacuum preloading model box test. The data were compared after the test. The mechanisms of the two different sludge preconditioning methods on the LS's consolidation were analyzed. The results show that: after freezing, the specific resistance of LS decreases obviously, the overall particle size increases, the content of small particles decreases. Too fast freezing rate is not conducive to the LS's dewatering. After preconditioning (F/T and FeCl3) combined with vacuum preloading, the volume reduction ratio was 57.1% and 41.1% respectively, the water content was reduced from 73.4% to 53.7% and 58.1%, and the unconfined compressive strength(UCS) was improved from 15.5 kPa to 50.9 kPa and 77.3 kPa. The total water discharge, drainage rate, volume reduction, and water content of freeze-thaw preconditioned LS are better than FeCl3 preconditioned, while FeCl3 preconditioned LS has higher UCS. F/T can aggregate small sludge particles but the acidification and hydrolysis of FeCl3 always produce small particle, which is not conducive to the consolidation of LS during vacuum preloading.

Clinical analysis and predictive factors associated with improved visual acuity of infectious endophthalmitis.

BACKGROUND: To describe the clinical characteristics and analyze the predictive factors associated with improved visual acuity of 359 patients with infectious endophthalmitis. METHODS: This study retrospectively analyzed 359 eyes of 359 patients with infectious endophthalmitis from January 2014 to December 2018. The findings summarized some epidemiological characteristics of these patients, including age, sex, occupation, patient visit time, etiology, causative organisms, therapy, and best-corrected visual acuity. Multivariate logistic regression was performed to predict the relative factors of improved visual acuity (VA). RESULTS: Overall, 283 (78.83%) patients were male. The mean age was 48.0 ± 18.27 years. Ocular trauma, especially open globe injuries (246, 68.5%) was the most common etiology of infectious endophthalmitis in this study. The etiologies of infectious endophthalmitis were open globe injuries (68.5%), intraocular surgery (22.6%), and corneal ulcer-associated (6.7%) and endogenous causes (2.2%). In the etiology classification and visual acuity improvement group, had statistically significant differences in factors such as age, sex, patient visit time, pre-therapy visual acuity, etc. The average Logarithm of the Minimum Angle of Resolution (logMAR) best-corrected visual acuity on pre-therapy was 2.28 ± 0.60, and it had significantly improved to 1.67 ± 0.83 post-therapy (P < 0.05). Logistic regression analysis showed that visit time > 7 day (P = 0.034, OR = 0.522, 95% CI: 0.286-0.953), pre-therapy VA ≦logMAR 2.3 (P = 0.032, OR = 1.809, 95% CI: 1.052-3.110), post-surgical (vs. posttraumatic; P = 0.023, OR = 2.100, 95% CI: 1.109-3.974), and corneal ulcer-associated etiologies (vs. posttraumatic; P = 0.005, OR = 0.202, 95%CI: 0.066-0.621) were significantly associated with improved visual acuity after adjusting for possible confounding factors. CONCLUSIONS: Among the patients with infectious endophthalmitis, middle-aged male, especially farmers and workers, accounted for a large proportion. Open globe injuries were the main cause and the gram-positive bacteria were the major causative organisms. The final visual outcomes seemed to vary according to the type of endophthalmitis, but early treatment and good initial visual acuity were important factors for visual acuity improvement.

Tilianin Protects Diabetic Retina through the Modulation of Nrf2/TXNIP/NLRP3 Inflammasome Pathways.

Oxidative stress and inflammation are regarded as prime reasons for the progression and development of diabetic retinopathy. Currently, nuclear factor erythroid-2-related factor 2 (Nrf2), thioredoxin interacting protein (TXNIP) and NLRP3 inflammasome pathways are under increasing focus in research on oxidative stress and inflammation-related diseases. On the other hand, tilianin (TN) has received much attention because of its various pharmacological properties. Based on results of these studies, this investigation was performed to inspect the therapeutic efficiency of TN on the retina in diabetic rats. Rats were arbitrarily assigned to three groups: control group, diabetic group, and diabetic plus TN (20 mg/ kg body weight for 42 days, orally) group. TN supplementation in diabetic rats, their food intake, fasting blood glucose status, glycosylated hemoglobin (HbA1c) levels were drastically reduced, and there was a marked augmentation in serum insulin status. TN treatment of diabetic rats increased mRNA expression of Nrf2 and its target gene, HO-1, and noticeably decreased the malondialdehyde status. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidases (GPX) were increased relative to diabetic rats. Furthermore, administering TN to the diabetic rats resulted in decreased expression of TXNIP, NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and IL-1ß proteins and decreased distribution of TXNIP, NLRP3, ASC, and caspase-1 proteins in retinas. In addition, TN treatment ameliorated morphological and morphometric changes in the retinas of diabetic rats. Together, all of these findings provide clear evidence that TN treatment of diabetic rats attenuated diabetic retinal changes through its hypoglycemic, antioxidant, and anti-inflammatory properties. The antioxidant and anti-inflammatory effects in diabetic retinas occur at least in part through the modulation of Nrf2/TXNIP/NLRP3 inflammasome pathways, which may have remedial benefits in the healing of diabetic retinopathy.

Ripasudil alleviated the inflammation of RPE cells by targeting the miR-136-5p/ROCK/NLRP3 pathway.

BACKGROUND: Inflammation of RPE cells led to different kinds of eye diseases and affected the normal function of the retina. Furthermore, higher levels of ROCK1 and ROCK2 induced injury of endothelial cells and many inflammatory diseases of the eyes. Ripasudil, which was used for the treatment of glaucoma, was one kind of the inhibitor of ROCK1 and ROCK2, but whether ripasudil could relieve the LPS-induced inflammation and damage of RPE cells was not clear. METHODS: We used LPS to stimulate ARPE-19 cells, the RPE cell line. After that, we detected the levels of ROCK1 and ROCK2 by western-blotting after the stimulation of LPS and treatment of ripasudil. Then luciferase reporter assays were used to confirm the targeting effect of miR-136-5p on ROCK1 and ROCK2. At last, the levels of NLRP3, ASC, caspase1, IL-1ß and IL-18 were detected with the western-blotting after the knockdown of miR-136-5p. RESULTS: The levels of ROCK1, ROCK2 and miR-136-5p in ARPE-19 cells were promoted after the stimulation of LPS. After the treatment of ripasudil, the expression levels of ROCK1, ROCK2 and miR-136-5p were suppressed. The expression of ROCK1 and ROCK2 was targeted and inhibited by the miR-136-5p. The levels of inflammation related proteins NLRP3, ASC, caspase1, IL-1ß and IL-18 was also inhibited after the treatment of ripasudil. However, the expression of these proteins was rescued after the knockdown of miR-136-5p. CONCLUSION: Ripasudil relieved the inflammatory injury of RPE cells by upregulating miR-136-5p, therefore inhibiting the expression of ROCK1, ROCK2, NLRP3, ASC, caspase1, IL-1ß and IL-18.

MiR-142-5p Acts as a Significant Regulator Through Promoting Proliferation, Invasion, and Migration in Breast Cancer Modulated by Targeting SORBS1.

BACKGROUND: Numerous researches have demonstrated that miR-142-5p plays significant roles in several cancers, although the functional characteristic of miR-142-5p in breast cancer has not been determined. This study is designed to explore the biological significance of miR-142-5p in breast cancer clinical implication and mechanism of action. METHODS: The differential expression patterns of miR-142-5p and Sorbin and SH3 domain-containing protein 1 and correlations between them and clinical significances were analyzed based on data from database. The expression levels of miR-142-5p in breast cancer cells were detected using quantitative real-time polymerase chain reaction. Cell counting kit-8, transwell, and wound healing assays were used to explore the potential functions of miR-142-5p in breast cancer cells. In addition, bioinformatics prediction analysis and luciferase reporter assay were utilized to predict and identify the potential target gene of miR-142-5p. A rescue experiment was conducted by transfecting miR-142-5p inhibitors and si-Sorbin and SH3 domain-containing protein 1 into cells to explore miR-142-5p/Sorbin and SH3 domain-containing protein 1 pairs on breast cancer cells behaviors. RESULTS: The analysis results showed that miR-142-5p was highly expressed in patients with breast cancer, while Sorbin and SH3 domain-containing protein 1 presented a trend of low expression. The clinical significances analysis suggested that the overexpression of miR-142-5p is closely correlated with metastasis, while low expression of Sorbin and SH3 domain-containing protein 1 is correlated with clinicopathological characteristics and poor overall survival in patients with breast cancer. In vitro exploration, the expression of miR-142-5p was upregulated in breast cancer cells and inhibition of miR-142-5p expression significantly reduced the proliferation, invasion, and migration of breast cancer cells. Through rescue experiments, breast cancer cells proliferation, invasion, and migration reduction induced by silencing of miR-142-5p were reversed via knockdown Sorbin and SH3 domain-containing protein 1. CONCLUSION: Our findings insinuate that miR-142-5p functions as a positive regulator of promoting breast cancer cells biological behaviors and clinical metastasis, possibly regulated by targeting Sorbin and SH3 domain-containing protein 1, thus providing valuable information in the development of preventive or even therapeutic strategies for utilizing miR-142-5p as a promising target.

An integrated bioinformatics analysis of potential therapeutic targets among matrix metalloproteinases in breast cancer.

Breast cancer (BC) is one of the most aggressive malignancies worldwide among females. Matrix metalloproteinases (MMPs), as the most abundant class of non-serine proteases present in invasive and metastatic tumors, can regulate a variety of alterations in the microenvironment during tumor progression. However, the differential expression of MMPs and its prognostic values in BC is yet to be elucidated. In this research, using the ONCOMINE dataset, The Cancer Genome Atlas, Breast Cancer Gene-Expression Miner v4.1 (Bc-GenExMiner), Kaplan-Meier Plotter and cBioPortal, the transcriptional MMPs and survival outcome data of patients with BC was compared. It was indicated that mRNA levels of MMP1/3/9/10/11/12/13 were increased compared with non-tumor tissues, whereas mRNA expression of MMP2/16/19/23B/28 was lower in BC tissues. Kaplan-Meier plots showed that high mRNA levels of MMP2/10/16/19/20/23B/27 in patients with BC were associated with better recurrence-free survival. In contrast, high MMP1/8/9/11/12 conferred worse RFS rate. Meanwhile, high transcription levels of MMP1/3/11/12/13 predicted shorter distant metastasis-free survival, while high levels of MMP1/12 demonstrated worse overall survival in patients with BC. From Bc-GenExMiner, it was indicated that high expression of MMP16/20 was correlated with better prognosis, while MMP1/9/11/12/13/14/15 exerted a negative effect on patient prognosis. The integrative bioinformatics analysis performed in the present study suggests that MMP1/9/12/16, compared with other MMPs, are potentially appropriate targets for targeted therapy in patients with BC.

MicroRNA-873 inhibits colorectal cancer metastasis by targeting ELK1 and STRN4.

MicroRNAs (miRNAs) are a group of small non-coding RNAs that directly bind to the 3'-untranslated-region (3'UTR) of mRNA, thereby blocking gene expression post-transcriptionally. Accumulating evidence prove that microRNA-873 (miR-873) functions as a promoter or suppressor in various cancers, while whether it affects the progression of colorectal cancer (CRC) is yet unknown. Here we found that miR-873 was downregulated in human CRC clinical samples, mouse CRC specimens and cell lines with high metastatic potential. We also demonstrated that low miR-873 expression was closely associated with poor prognosis of CRC. Overexpressing miR-873 suppressed proliferation and metastasis of CRC cells both in vitro and in vivo, while inhibiting miR-873 expression promoted the proliferation, migration and invasion in vitro. Moreover, miR-873 exerted its function by perturbing the ERK-CyclinD1 pathway and the epithelial-mesenchymal transition (EMT) process. Furthermore, we revealed that miR-873 acted as a tumor-suppressive microRNA by directly binding to the 3'UTRs of ELK1 and STRN4 and suppressed their expression. Our study uncovered an inhibitory role of miR-873 in CRC progression and might provide a promising marker for CRC diagnosis and prognosis.

Correction: NLRP6 targeting suppresses gastric tumorigenesis via P14ARF-Mdm2-P53-dependent cellular senescence.

[This corrects the article DOI: 10.18632/oncotarget.22876.].

Overexpression of COUP­TFII suppresses proliferation and metastasis of human gastric cancer cells.

The abnormal expression of the chicken ovalbumin upstream promoter transcription factor 2 (COUP­TFII) is associated with numerous forms of cancer, including gastric, prostate, colon and lung cancer. However, previous studies investigating the association between COUP­TFII expression and the occurrence, recurrence, invasion and metastasis of gastric cancer are limited in number. In the present study, it was revealed that the expression of COUP­TFII is significantly reduced in gastric carcinoma tissues compared with normal gastric mucosa cells (GES­1). In addition, the expression of COUP­TFII was also reduced in gastric cancer cell lines compared with GES­1 cells. Furthermore, it was revealed that ectopic expression of COUP­TFII was able to suppress the proliferation, migration and invasion of gastric cells, as well as inhibit hepatic metastasis, in vivo. In addition, it was demonstrated that COUP­TFII knockdown was able to promote the proliferation, migration and invasion of GES­1 cells in vitro. Furthermore, database analysis suggested that COUP­TFII expression in patients with gastric cancer is correlated with clinical stage classification and increased expression levels of COUP­TFII improved overall survival rates in patients with gastric cancer. The results of the present study suggest that COUP­TFII functions as a significant regulatory suppressor of gastric cancer growth and metastasis, and suggests that COUP­TFII may serve as a novel diagnostic and prognostic biomarker for gastric cancer metastasis.

LRP6 targeting suppresses gastric tumorigenesis via P14ARF-Mdm2-P53-dependent cellular senescence.

NLRP6, a member of the Nod-like receptor family, protects against chemically induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms involved in this NLRP6-mediated protection remain unclear. Here, we show that NLRP6 was down-regulated in approximately 75% of primary gastric cancer cases and exhibited significant associations with advanced clinical-stage lymph node metastasis and poor overall survival. Functional studies established that ectopic overexpression or down-regulation of NLRP6 inhibited cancer cell proliferation by inducing cell cycle arrest at the G1 phase via P21 and Cyclin D1 both in vitro and in vivo. Activation of the P14ARF-P53 pathway played a crucial role in the observed cellular senescence. We further demonstrated that ectopic overexpression of NLRP6 combined with inactivation of NF-κB(p65) and Mdm2 activates P14ARF-P53 to promote the senescence of gastric cancer cells. These findings indicate that NLRP6 functions as a negative regulator of gastric cancer and offer a potential new option for preventing gastric cancer.

miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2.

miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy.