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Nonstructural carbohydrates (NSCs) reflect the carbon balance in trees and play a central role in their responses to environmental stresses. However, our understanding of tree NSC storage dynamics under environmental stress is unclear. Here, we quantified the deciduous conifer Larix principis-rupprechtii at five altitudes on Luya Mountain, North-Central China. We measured NSCs in different organs and simultaneously monitored environmental variables during the growing seasons in 2018 and 2019. The results showed that temperature was the main environmental factor affecting tree NSCs. Furthermore, as the soil–atmosphere temperature gradient decreased, the concentrations of soluble sugars in the needles increased while their starch decreased, as well as the concentrations of starch in the shoots, stems, and roots increased. These results may indicate that temperature gradients may assist carbohydrate allocation within individual trees. The NSCs, especially starch, in the needles increased with lower soil moisture, and the soluble sugars and starch in the needles and shoots increased with a higher vapor pressure deficit. The soluble sugars in the stems were significantly affected by soil moisture, and the NSCs in the roots were mainly affected by temperature. These results provide new insights to improve our understanding of the environmental stress effects on future forest C balances. [ABSTRACT FROM AUTHOR]

We report that circDDX21 functions as a sponge for miR-1264 and regulates QKI expression, thus repressing the progression of triple-negative breast cancer (TNBC). (O-P) The clone formation ability of the circDDX21 knockdown cells transfected with the miR-1264 inhibitor (*p < .05, **p < .01, ***p < .001) gl In previous study, miR-1264 was confirmed to be a target of another non-coding RNA, SOCS2-AS1. (Q and R) The clone formation ability of the miR-1264 inhibited cells transfected with QKI (*p < .05, **p < .01, ***p < .001) gl Thus far, we have confirmed that circDDX21 functions as a sponge for miR-1264, to regulate the expression of QKI. CircRNA DDX21 acts as a prognostic factor and sponge of miR-1264/QKI axis to weaken the progression of triple-negative breast cancer. [Extracted from the article]

Objective: The objective of the study was to assess the impact of multifaceted clinical pharmacist-led antimicrobial stewardship (AMS) program on the rational use of antibiotics for patients who receive vascular and interventional radiology therapies. Methods: A quasi-experimental retrospective intervention design with a comparison group was applied to the practice of antibiotic use in the department of vascular and interventional radiology in a Chinese tertiary hospital. We used difference-in-differences (DID) analysis to compare outcomes before and after the AMS intervention between the intervention group and control group, to determine whether intervention would lead to changes in irrationality of antibiotic prescribing, antibiotic utilization, cost of antibiotics, and length of hospital stay. Results: The DID results showed that the intervention group was associated with a reduction in the average consumption of antibiotics (p = 0.017) and cost of antibiotics (p = 0.006) and cost per defined daily dose (DDD) (p = 0.000). There were no significant differences in the mean change of total costs and length of stay between the two groups (p > 0.05). The average inappropriate score of perioperative antimicrobial prophylaxis in the intervention group declined by 0.23, while it decreased by 0.02 in the control group [0.21 (95% CI, −0.271 to −0.143); p = 0.000]. The average inappropriate score of non-surgical antimicrobial prophylaxis in the intervention group declined by 0.14, while it increased by 0.02 in the control group [0.16 (95% CI, −0.288 to −0.035); p = 0.010]. The average inappropriate score of the therapeutic use of antibiotics in the intervention group declined by 0.07, while it decreased by 0.01 in the control group [0.06 (95% CI, −0.115 to −0.022); p = 0.003]. Conclusions: This study provides evidence that implementation of AMS interventions was associated with a marked reduction of antibiotic use, cost of antibiotics, and irrationality of antibiotic prescribing in China. [ABSTRACT FROM AUTHOR]

Ubiquitin C-terminal hydrolase L1 (UCHL1), which is a deubiquitinating enzyme, is known to play a role in chemoresistance in cancers. However, its potential roles and mechanisms in the chemoresistance of breast cancer (BC) remain unclear. In this study, we examined its expression in patients with BC and employed Kaplan–Meier analysis and the log-rank test for survival analyses. It was found that up-regulated UCHL1 expression was positively associated with both chemoresistance and poor prognosis, especially in patients with HER2+ BC. Moreover, UCHL1 expression was elevated in HER2+ BC cells (SK-BR-3 and BT474). Similarly, doxorubicin (DOX)-resistant BC cells (MCF-7/DOX) had higher UCHL1 levels than MCF-7 cells. CCK-8 assay showed that BC cells with higher UCHL1 levels were more resistant to DOX. Furthermore, by inhibiting UCHL1 in BC cells with elevated UCHL1 expression, we demonstrated that UCHL1 promoted DOX-resistance in BC. Mechanistically, UCHL1 probably promoted DOX-resistance of BC by up-regulating free fatty acid (FFA) synthesis, as exhibited by reduced FFA synthase expression and resurrected DOX-sensitivity upon UCHL1 inhibition. Overall, UCHL1 up-regulation is associated with DOX-resistance and poor prognosis in patients with HER2+ BC. UCHL1 induces DOX-resistance by up-regulating FFA synthesis in HER2+ BC cells. Thus, UCHL1 might be a potential clinical target for overcoming DOX resistance in patients with HER2+ BC. [ABSTRACT FROM AUTHOR]

Background and aims: Breast cancer-related death is attributable mainly to metastasis. Inflammatory breast cancer (IBC) is an infrequent subtype of breast cancer that shows a relatively high rate of metastasis. In this study, we aimed to compare the metastatic patterns and prognostic outcomes of IBC and non-inflammatory breast cancer (non-IBC). Methods: We extracted data between 2010 and 2014 from the Surveillance, Epidemiology and End Results (SEER) database. The Chi-square test and Fisher's exact test were used to compare the categorical parameters among different groups. Logistic regression was applied for multivariate analysis. The Kaplan–Meier method and multivariate Cox regression models were performed to analyze prognosis. Results: We enrolled 233,686 breast cancer patients between 2010 and 2014 in our research, including 2806 IBC and 230,880 non-IBC patients. Compared with the non-IBC group, the IBC group tended to have a higher incidence of the human epidermal growth factor receptor 2 positive (HER2+) and triple-negative breast cancer (TNBC) subtypes, older age, a higher rate of unmarried status, a lower incidence of black race, poorer tumor differentiation, larger tumor sizes, and a higher frequency of regional lymph node invasion. IBC and non-IBC shared similar trends in molecular subtypes among different metastatic organs. The percentage of the hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2–) subtype decreased gradually in patients with lung (IBC 42.5%, non-IBC 55.7%), distant lymph node (IBC 41.5%, non-IBC 54.6%), liver (IBC 31.1%, non-IBC 46.7%), and brain (IBC 30.6%, non-IBC 47.9%) metastases compared with that in patients with bone (IBC 50.8%, non-IBC 69.0%) metastasis in both cohorts. In both the IBC and non-IBC cases, the proportion of visceral metastases increased in the TNBC subtype, especially brain metastasis (IBC 26.4%, non-IBC 21.2%), which had the largest increase. The frequencies of all sites (bone, lung, liver, brain, and distant lymph node) in IBC were much higher than those in non-IBC (bone: IBC 21.1%, non-IBC 3.0%; lung: IBC 11.4%, non-IBC 1.4%; liver: IBC 9.6%, non-IBC 1.2%; brain: IBC 2.6%, non-IBC 0.3%; distant lymph node: IBC 12.9%, non-IBC 1.0%). The most frequent bi-site metastasis was the bone and liver (IBC 2.5%, non-IBC 0.3%), and the most frequent tri-site combination was the bone, lung, and liver (IBC 1.1%, non-IBC 0.2%). Kaplan–Meier curves and multivariate Cox regression models suggested that the IBC cohort had poorer overall survival [hazard ratio (HR) 1.602, 95% confidence interval (CI) 1.496–1.716, p < 0.001] and breast cancer-specific survival (HR 1.511, 95% CI 1.402–1.628, p < 0.001) than the non-IBC cohort. Furthermore, univariate and multivariate analyses indicated that IBC was an independent prognostic factor in patients with different metastatic sites. Conclusion: IBC and non-IBC patients presented with different metastatic frequencies, clinical features and prognostic outcomes. Our findings provide more information for therapeutic decision making and clinical study designs. [ABSTRACT FROM AUTHOR]

Alternaria alternata is the major threat to postharvest storage of jujube (Ziziphus jujuba Mill.) fruit. We found that natural A. alternata infection can cause very typical phenotype of 'green ring' and 'red ring' surrounding the disease spot on the jujube fruit. The phenotype was successfully modeled and constructed on jujubes by artificial inoculation with the pathogen. Furthermore, the pathogenic infection is evidenced essential to the onset of the phenotype. The 'red ring' circle is proved to be pre-fixed to block the 'green ring' area as a battlefield combating the pathogen's attack. We monitored the global transcriptomic profiling of 'green ring' and 'red ring' tissues from jujubes infected with A. alternata, in comparison with the mock-inoculated fruit and the control intact fruit. Large amount of differentially expressed genes were obtained in 'green ring', followed by 'red ring'. Transcriptional alterations associated with the core and peripheral phenylpropanoid and lignin pathways, plant hormonal metabolisms were greatly influenced in the 'green ring' and 'red ring' by the A. alternata infection. The integrated analysis of transcriptomic profiling and metabolic changes revealed the differentially but delicately coordinated activation of these biological processes in the 'green ring' and 'red ring' on jujubes in defensing the fungal infection. [ABSTRACT FROM AUTHOR]

• Different periods were determined according to the pattern of the daily stem cycle. • Interspecific differences in tree water deficit declined with elevations. • Spruce showed greater daily amplitude than larch in spring rehydration rather than summer growth. • Opposite responses of stem water relations to high vapor pressure deficit between the two conifers. Internal water storage in the stem provides additional water for transpiration and photosynthesis and thus ensures tree hydraulic safety and growth under stressed conditions. Comprehensive understandings in elevation- and species-specific patterns of stem water relations and the underlying mechanism could shed light on the physiological foundation of forest conservation and management in the montane area. Here, stem radius variations of co-occurring Larix principis-rupprechtii and Picea meyeri were monitored at three sites of different elevations (2200 m, 2400 m, and 2600 m a.s.L.) in 2018 and 2019 using point dendrometers. The seasonal cycle was divided into four periods: spring rehydration, summer growth, autumn contraction, and winter dormancy. Tree water deficit-induced stem shrinkage (TWD) during the summer growth and daily stem cycles in each period were extracted and compared between species and among elevations, and their responses to environmental factors were determined. The results showed an elevational trend for averaged TWD in L. principis-rupprechtii instead of P. meyeri. TWD in both tree species had a closer relationship with vapor pressure deficit (VPD), while the TWD showed piecewise changes with species-specific differences as the VPD increased. The daily amplitude of L. principis-rupprechtii was smaller than that of P. meyeri in periods of winter dormancy and spring rehydration, however, the comparison was opposite during summer growth and autumn contraction. Furthermore, the daily amplitude of L. principis-rupprechtii and P. meyeri had different responses to the air and soil hydrothermal conditions in different periods over the year. Our study highlights interspecific water-use behaviors between larch and spruce, indicating their contrasting responses to a global increase in drought stress, especially in low elevations. [ABSTRACT FROM AUTHOR]

Introduction: Transforming acidic coiled-coil containing protein 3 (TACC3) exerts a vital role in cancer progression by modulating cell division and facilitating tumor growth. Given the lack of comprehensive research on the pancancer implications of TACC3, our study aimed to analyze the functional role of TACC3 in pancancer and validate it through experimental investigations in lung adenocarcinoma. Methods: We first employed various bioinformatics techniques to investigate the expression and prognostic significance of TACC3 in pancancer. Subsequently, we analyzed the correlation between TACC3 and immune infiltration, immune checkpoints, drug sensitivity, as well as the prediction of immune therapy response. Finally, we validated the association between TACC3 and the proliferation of lung adenocarcinoma, as well as its resistance to docetaxel, through in vitro experiments. Results: Here, TACC3 exhibited high expression in human cancers and was associated with poor prognosis in various cancer types. It was also involved in immune infiltration and demonstrated a strong predictive ability for immune therapy response. Through drug sensitivity prediction, we further identified a potential association between TACC3 and docetaxel resistance, which was subsequently validated in lung adenocarcinoma. Conclusion: Our investigation of TACC3 revealed its potential as a promising target both for immunosuppression and docetaxel resistance in pancancer, especially in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Corrigendum: USP5 Promotes Metastasis in Non-Small Cell Lung Cancer by Inducing Epithelial-Mesenchymal Transition via Wnt/ -Catenin Pathway Keywords: non-small cell lung cancer; metastasis; epithelial-to-mesenchymal transition; ubiquitin-specific protease 5 (USP5); -catenin EN non-small cell lung cancer metastasis epithelial-to-mesenchymal transition ubiquitin-specific protease 5 (USP5) -catenin 1 1 1 06/26/20 20200624 NES 200624 The correspondence order was incorrect in the original article. Non-small cell lung cancer, metastasis, epithelial-to-mesenchymal transition, ubiquitin-specific protease 5 (USP5), -catenin. [Extracted from the article]

Fine-resolution studies of stem radial variation over short timescales throughout the year can provide insight into intra-annual stem dynamics and improve our understanding of climate impacts on tree physiology and growth processes. Using data from high-resolution point dendrometers collected from Platycladus orientalis (Linn.) trees between September 2013 and December 2014, this study investigated the daily and seasonal patterns of stem radial variation in addition to the relationships between daily stem radial variation and environmental factors over the growing season. Two contrasting daily cycle patterns were observed for warm and cold seasons. A daily mean air temperature of 0 °C was a critical threshold that was related to seasonal shifts in stem diurnal cycle patterns, indicating that air temperature critically influences diurnal stem cycles. The annual variation in P. orientalis stem radius variation can be divided into four distinct periods including (1) spring rehydration, (2) the summer growing season, (3) autumn stagnation, and (4) winter contraction. These periods reflect seasonal changes in tree water status that are especially pronounced in spring and winter. During the growing season, the maximum daily shrinkage (MDS) of P. orientalis was positively correlated with air temperature (Ta) and negatively correlated with soil water content (SWC) and precipitation (P). The vapor pressure deficit (VPD) also exhibited a threshold-based control on MDS at values below or above 0.8 kPa. Daily radial changes (DRC) were negatively correlated with Ta and VPD but positively correlated with relative air humidity (RH) and P. These results suggest that the above environmental factors are associated with tree water status via their influence on moisture availability to trees, which in turn affects the metrics of daily stem variation including MDS and DRC. [ABSTRACT FROM AUTHOR]

Investigations on primary and secondary growth in co-occurring species will aid in assessment of the physiological adaptation of species and the prediction of forest stand structure dynamics. To explore the correlation and coordination between primary and secondary growth, we monitored the leaf phenology, shoot elongation, and stem growth of co-occurring Larix principis-rupprechtii Mayr. and Picea meyeri Rehd. et Wils. in an alpine habitat, Luya Mountain (North-Central China), during the growing season of 2014. We measured bud development on terminal branches three days per week by direct observations and intra-annual stem xylem formation at weekly intervals by the microcores method. The onset sequence of three organs was the needle, shoot, and stem, without species-specific differences. Needles appeared one month earlier than stem growth in larch, while it was only one week earlier in spruce. The duration of needle growth was the shortest, followed by the shoot and stem. The timing of primary growth (i.e., onset, end, and maximum growth rate) between the two species was asynchronous, but secondary growth was synchronic with the same date of the maximum growth rate occurrence, potentially indicating species competition for resources. Unlike larch, spruce staggered growth peaks among different organs, which may effectively mitigate trees' internal competition for resources. Soil temperature was positively correlated with both shoot and stem growth in the two species, whereas air temperature and soil water content were positively correlated with needle growth only in larch. Therefore, it can be inferred that the spruce will probably outcompete the larch at cold alpine treeline sites due to its high adaptability to acquiring and allocating resources. These results provide insight into the potential physiological correlation between primary and secondary growth and allow better prediction of future climate change effects on forest ecosystem productivity. [ABSTRACT FROM AUTHOR]

• The Weibull function was used to fit stem radius variations in cold seasons. • Stem shrinkage in Picea meyeri was greater on the forest edge after stem freeze. • The diurnal temperature range regulated the freeze-induced seasonal and diurnal variations in stem size. • Stem freeze or thaw was active when the daily minimum air temperature was around −2.5 °C. Dendrometer-derived stem radius variations (SRV) have been demonstrated as useful tools to test cold acclimation, which could reflect the tree water (ice) balance in winter and thus the frost stress. However, most previous studies focus on stem increment and water relations during growing seasons, stem radius variations in cold seasons and the underlying tree physiological information are not fully exploited, limiting our understanding of the response of mid- and high-latitudinal forests to warming winter. Hourly SRV in spruces (Picea meyeri) across an elevational transect of 700 m were observed over 6 consecutive years (2012–2017) in the present study. Elevation-specific variations in the onset of stem freeze and thaw, and the magnitude of seasonal and diurnal SRV in cold seasons were explored, and ultimately their dominant environmental factors were determined. Before stem freeze, seasonal and diurnal SRV showed linear trends with elevation, which were mainly affected by air and soil water conditions. Whereas, after stem freeze, the seasonal SRV and thus the stem dehydration was greater at the lower and upper limits of the forest belt, and the daily amplitude of freeze-thaw cycles was greater at high elevations. The diurnal air temperature range dominantly controlled the SRV on different time scales after stem freeze. Stem freeze and thaw in P. meyeri was active when the daily minimum air temperature was -2.5 °C in our study region. The onset of stem freeze and thaw advanced and delayed with elevation corresponding to a rate of 5.2 and 7.5 days/ °C when adjusted for the monitored lapse rate of 0.63 °C per 100 m, respectively. Together these findings highlight the value of high-precision variations in stem size to indicate the potential freezing stress, and trees growing at high elevations might suffer greater stress caused by frost dehydration and freeze-thaw under ongoing climate change. [ABSTRACT FROM AUTHOR]

Ilex cornuta Lindl. et Paxt. (Aquifoliaceae family) belongs to the Ilex genus. The leaves of this plant are used for the popular herbal tea "Ku-Ding-Cha" in China due to their health benefits for sore throat, obesity and hypertension. Our previous studies have shown that the extract of Ilex cornuta root exerts cardioprotective effects in rat models of myocardial ischaemic injury, and several new kinds of triterpenoid saponins from Ilex cornuta (TSIC) have protective effects against hydrogen peroxide (H2O2)-induced cardiomyocyte injury. The aim of this study was to clarify the underlying mechanisms by which TSIC protect against H2O2-induced cardiomyocyte injury. An H2O2-treated H9c2 cardiomyocyte line was used as an in vitro model of oxidation-damaged cardiomyocytes to evaluate the effects of TSIC. Apoptosis was detected with CCK-8 and annexin V assays and via analysis of the levels of apoptosis-associated proteins or genes. The underlying mechanisms related to Akt signalling, Ezh2 expression and activity, and ROS were clarified by Western blotting, quantitative PCR, flow cytometry and rescue experiments. TSIC protected H9c2 cells from H2O2-induced apoptosis. This effect of TSIC was attributable to inhibition of Ezh2 activity, as exhibited by attenuation of H2O2-induced Akt signalling-dependent phosphorylation of Ezh2 at serine 21 (pEzh2 S21) upon TSIC pretreatment. In addition, feedback pathway between Akt-dependent Ezh2 phosphorylation and ROS was involved in TSIC-mediated protection of H9c2 cells from apoptosis. Our findings indicate a pivotal role of the pEzh2 S21 network in TSIC-mediated protection against cardiomyocyte apoptosis, potentially providing evidence of the mechanism of TSIC in the treatment and prevention of cardiovascular diseases. Image 1 [ABSTRACT FROM AUTHOR]

The addition of olanzapine to fluoxetine produces an antidepressant effect on fluoxetine nonresponders. Promoting hippocampal neurogenesis is associated with the successful treatment of depression. The present study aimed to investigate the interaction of olanzapine and fluoxetine in regulating neurogenesis. We found that fluoxetine alone does not affect cell proliferation and inhibits the neuronal differentiation of cultured neural stem cells (NSCs), but promotes NSCs proliferation and exerts no effect on neuronal fate when NSCs are cocultured with neurons. In addition, fluoxetine alone also does not alter the neuronal fate of newborn hippocampal cells in vivo. Although fluoxetine treatment elicits different results, our data consistently show that olanzapine alone does not affect the proliferation and neuronal differentiation of NSCs. The combination of olanzapine and fluoxetine has no profound effect on NSCs proliferation compared with fluoxetine alone, but olanzapine add-on treatment produces a greater number and percentage of differentiated neurons from NSCs. Further investigations are needed to explore the underlying mechanisms of the increased neurogenesis caused by the combination of olanzapine with fluoxetine., (© 2022 The Author(s).)

Cathepsin L (CTSL), a lysosomal acid cysteine protease, is found to play a critical role in chemosencitivity and tumor progression. However, the potential roles and molecular mechanisms of CTSL in chemoresistance in neuroblastoma (NB) are still unclear. In this study, the correlation between clinical characteristics, survival and CTSL expression were assessed in Versteeg dataset. The chemoresistant to cisplatin or doxorubicin was detected using CCK-8 assay. Western blot was employed to detect the expression of CTSL, multi-drug resistance proteins, autophagy-related proteins and apoptosis-related proteins in NB cells while knocking down CTSL. Lysosome staining was analyzed to access the expression levels of lysosomes in NB cells. The expression of apoptosis markers was analyzed with immunofluorescence. Various datasets were analyzed to find the potential protein related to CTSL. In addition, a subcutaneous tumor xenografts model in M-NSG mice was used to assess tumor response to CTSL inhibition in vivo . Based on the validation dataset (Versteeg), we confirmed that CTSL served as a prognostic marker for poor clinical outcome in NB patients. We further found that the expression level of CTSL was higher in SK-N-BE (2) cells than in IMR-32 cells. Knocking down CTSL reversed the chemoresistance in SK-N-BE (2) cells. Furthermore, combination of CTSL inhibition and chemotherapy potently blocked tumor growth in vivo . Mechanistically, CTSL promoted chemoresistance in NB cells by up-regulating multi-drug resistance protein ABCB1 and ABCG2, inhibiting the autophagy level and cell apoptpsis. Furthermore, we observed six datasets and found that Serglycin (SRGN) expression was positively associated with CTSL expresssion. CTSL could mediate chemoresistance by up-regulating SRGN expression in NB cells and SRGN expression was positively correlated with poor prognosis of NB patients. Taken together, our findings indicate that the CTSL promotes chemoresistance to cisplatin and doxorubicin by up-regulating the expression of multi-drug resistance proteins and inhibiting the autophagy level and cell apoptosis in NB cells. Thus, CTSL may be a therapeutic target for overcoming chemoresistant to cisplatin and doxorubicin in NB patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Du, Ding, Huang, Li, Yan, Tang, Ding, Zhu and Wang.)

Rationale : Resistance to pemetrexed (PEM)-based chemotherapy is a major cause of progression in non-small cell lung cancer (NSCLC) patients. The deubiquitinating enzyme UCHL1 was recently found to play important roles in chemoresistance and tumor progression. However, the potential roles and mechanisms of UCHL1 in PEM resistance remain unclear. Methods : Bioinformatics analyses and immunohistochemistry were used to evaluate UCHL1 expression in NSCLC specimens. Kaplan-Meier analysis with the log-rank test was used for survival analyses. We established PEM-resistant NSCLC cell lines by exposing them to step-wise increases in PEM concentrations, and in vitro and in vivo assays were used to explore the roles and mechanisms of UCHL1 in PEM resistance using the NSCLC cells. Results : In chemoresistant tumors from NSCLC patients, UCHL1 was highly expressed and elevated UCHL1 expression was strongly associated with poor outcomes. Furthermore, UCHL1 expression was significantly upregulated in PEM-resistant NSCLC cells, while genetic silencing or inhibiting UCHL1 suppressed resistance to PEM and other drugs in NSCLC cells. Mechanistically, UCHL1 promoted PEM resistance in NSCLC by upregulating the expression of thymidylate synthase (TS), based on reduced TS expression after UCHL1 inhibition and re-emergence of PEM resistance upon TS restoration. Furthermore, UCHL1 upregulated TS expression, which mitigated PEM-induced DNA damage and cell cycle arrest in NSCLC cells, and also conferred resistance to PEM and other drugs. Conclusions : It appears that UCHL1 promotes PEM resistance by upregulating TS in NSCLC cells, which mitigated DNA damage and cell cycle arrest. Thus, UCHL1 may be a therapeutic target for overcoming PEM resistance in NSCLC patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Ubiquitin-specific protease 5 (USP5) is a deubiquitinating enzyme that functions as an oncoprotein in a variety of human cancers. However, the expression and role of USP5 in the metastasis of non-small cell lung cancer (NSCLC) have not been addressed. In this study, we examined the expression and prognostic significance of USP5 in NSCLC. The results revealed that USP5 was overexpressed and correlated with metastasis and overall survival in NSCLC tissues. A further in vitro study revealed that the levels of USP5 protein in NSCLC cells were associated with epithelial-mesenchymal transition (EMT) markers. Furthermore, USP5 overexpression significantly enhanced, whereas USP5 silencing significantly decreased the expression of EMT proteins and migration and invasion of NSCLC cells. In addition, the results from western blotting demonstrated that USP5 regulated EMT via the Wnt/β-catenin signaling pathway. Further immunohistochemical analysis revealed that USP5 was significantly associated with the expression of β-catenin and EMT markers in NSCLC tissues. Overall, USP5 upregulation is associated with tumor metastasis and poor prognosis in patients with NSCLC. USP5 promotes EMT and the invasion and migration of NSCLC cells. Therefore, USP5 may serve as a novel prognostic biomarker and provide a potential target for the treatment of metastasis in NSCLC., (Copyright © 2020 Xue, Wu, Wang, Lu, Sun, Jin, Xie, Wang, Tan, Wang, Wang and Ding.)