High-precision multi-spectral radiation thermometry method based on the improved grey wolf optimization algorithm inversion.

In this paper, in order to rapidly measure the temperature of a high-temperature target in real time without emissivity data, a high-precision multispectral radiation temperature measurement method based on the improved grey wolf optimization (IGWO) algorithm is proposed. The method can automatically identify the emissivity models of different trends and realize the simultaneous estimation of temperature and emissivity without the emissivity hypothesis model. The IGWO algorithm is applied to the temperature test of a silicon carbide and tungsten material. The temperature test results show that the absolute and relative errors of the silicon carbide (the tungsten) are less than 3 K (4.5 K) and 0.25% (0.18%), respectively. The average time of the algorithm is 0.28 s. The IGWO algorithm can be expected to be applied to some high-precision temperature measurement scenarios.

Salivary microbiome diversity in Chinese children with various caries states.

OBJECTIVE: This study aimed to explore oral microbiome diversity among children with various caries status based on dmft scores. METHODS: A total of 320 children aged 3-5 years were recruited, with 66 healthy children and 254 children affected by dental caries. According to dmft scores, these children with dental caries were classified as "mild group" (dmft score 1-3), "moderate group" (dmft score 4-6), and "severe group" (dmft score 7-14). Healthy children with dmft score of 0 served as control group. Illumina MiSeq sequencing was employed to analyze all salivary samples collected from these children. RESULTS: The salivary microbial diversity among four groups was similar (p > 0.05). A total of five bacterial genera were highly abundant in the control group including Bergeyella, Acidimicrobiales, Acidimicrobiia, Halomonas, and Blautia (p < 0.05). For mild group, there were nine bacterial genera identified to be predominant: Porphyromonadaceae, Porphyromonas, Enterobacteriales, Enterobacteriaceae, Weissella, Leuconostocaceae, Alphaproteobacteria, Stenotrophomonas, and Rhizobiales (p < 0.05). Only one genus, Aggregatibacter was predominant in moderate group (p < 0.05). There were six bacterial genera (Alistipes, Lachnoclostridium, Escherichia-Shigella, Romboutsia, Sphingomonadales, and Denitratisoma) enriched in severe group (p < 0.05). CONCLUSION: Oral microbial profile was different in children with various caries status based on dmft scores. CLINICAL RELEVANCE: The results might be beneficial to deeply understand microbiological diversity of early childhood caries (ECC) at various stages and inform effective strategies for ECC prevention.

Research progress and clinical application prospects of miRNAs in oral cancer.

Oral cancer is one of the most common malignant tumors worldwide, and it is also one of the most important and difficult clinical problems to be solved. Due to the regional differences in diet culture, some areas have taken the 'hardest hit' of oral cancer cases. However, the existing clinical treatment methods (surgery as the main treatment method, radiotherapy and chemotherapy as the auxiliary ones) do not have satisfactory treatment effects; therefore, new diagnosis and treatment methods need to be developed and utilized. Micro RNAs (miRNAs), as a class of substances that play an important regulatory role in the development of tumors, have an important value in the diagnosis and treatment of various tumors. At the same time, many miRNAs have obvious expression differences in oral cancer tissues compared to normal tissues. Therefore, they may have diagnostic and therapeutic effects on oral cancer. In this review, we evaluate the miRNAs that play a regulatory role in the development of oral cancer and those that are expected to be applied in the diagnosis and treatment of oral cancer. At the same time, we summarize the important challenges that need to be addressed, aiming to provide evidence and suggestions for the application of miRNAs in the diagnosis and treatment of oral cancer.

Combined glycoprotein IIb/IIIa inhibitor therapy with ticagrelor for patients with acute coronary syndrome.

This study was to compare the efficacy and safety of combined glycoprotein IIb/IIIa inhibitor (GPI) and ticagrelor versus ticagrelor in patients with acute coronary syndrome (ACS). An observational study was conducted using the Improving Care for Cardiovascular Disease in China-ACS project. Totally, 13,264 patients with ACS and received combination therapy or ticagrelor therapy were analyzed. The primary outcome was the composite of major cardiovascular events (MACE: all-cause mortality, myocardial infarction [MI], stent thrombosis, cardiogenic shock, and ischemic stroke), and secondary outcomes included all-cause mortality, MI, stent thrombosis, cardiogenic shock, and ischemic stroke. The multivariable adjusted analysis indicated that combination therapy was associated with an increased risk of major cardiovascular events (MACE) (P = 0.001), any bleeding (P<0.001), and major bleeding (P = 0.005). Moreover, the multivariable adjusted for propensity score-matched (PSM) analysis suggested that combination therapy produced additional risk of MACE (P = 0.014), any bleeding (P<0.001), and major bleeding (P = 0.005). Moreover, PSM analysis suggested that combination therapy was associated with greater risk of stent thrombosis (P = 0.012) and intracranial bleeding (P = 0.020). Combined GPI and ticagrelor therapies did not have any beneficial effects on MACE, stent thrombosis, intracranial bleeding, any bleeding, or major bleeding.

Lack of associations between lactoferrin (LTF) and mannose-binding lectin 2 (MBL2) gene polymorphism and dental caries susceptibility.

OBJECTIVE: With the development of human genomics, the genetic factors associated with dental caries have receiving increasing attention. This study was performed to evaluate the relationship between lactoferrin (LTF) and mannose-binding lectin 2 (MBL2) gene single nucleotide polymorphisms (SNPs) and dental caries susceptibility in Chinese children. METHODS: This prospective case-control study included 360 unrelated children (aged 12-15 years) who received oral health examinations and questionnaire surveys. The children were divided into two groups by counting the numbers of decayed, missing, and filled teeth (DMFT/dmft): case group (n = 162, DMFT/dmft ≥ 1) and control group (n = 198, DMFT/dmft = 0); non-invasive saliva samples were collected to extract genomic DNA. Six SNPs (rs2073495C/G, rs1042073C/T, rs10865941C/T, and rs1126477A/G in LTF; rs7096206C/G and rs7095891G/A in MBL2) were tested by mass spectrometry. RESULTS: The study included 360 individuals with (85 boys and 77 girls) and without a history of caries (96 boys and 102 girls). There were no statistically significant differences in alleles and genotypes among the six SNPs between the two groups. CONCLUSION: There is no evidence that polymorphisms of LTF and MBL2 genes are associated with dental caries susceptibility in populations from northwest China; further confirmation is needed with larger sample sizes.

Nanomorphological and mechanical reconstruction of mesenchymal stem cells during early apoptosis detected by atomic force microscopy.

Stem cell apoptosis exists widely in embryonic development, tissue regeneration, repair, aging and pathophysiology of disease. The molecular mechanism of stem cell apoptosis has been extensively investigated. However, alterations in biomechanics and nanomorphology have rarely been studied. Therefore, an apoptosis model was established for bone marrow mesenchymal stem cells (BMSCs) and the reconstruction of the mechanical properties and nanomorphology of the cells were investigated in detail. Atomic force microscopy (AFM), scanning electron microscopy (SEM), laser scanning confocal microscopy (LSCM), flow cytometry and Cell Counting Kit-8 analysis were applied to assess the cellular elasticity modulus, geometry, nanomorphology, cell surface ultrastructure, biological viability and early apoptotic signals (phosphatidylserine, PS). The results indicated that the cellular elastic modulus and volume significantly decreased, whereas the cell surface roughness obviously increased during the first 3 h of cytochalasin B (CB) treatment. Moreover, these alterations preceded the exposure of biological apoptotic signal PS. These findings suggested that cellular mechanical damage is connected with the apoptosis of BMSCs, and the alterations in mechanics and nanomorphology may be a sensitive index to detect alterations in cell viability during apoptosis. The results contribute to further understanding of apoptosis from the perspective of cell mechanics.

FAM163A, a positive regulator of ERK signaling pathway, interacts with 14-3-3ß and promotes cell proliferation in squamous cell lung carcinoma.

PURPOSE: FAM163A, also called neuroblastoma-derived secretory protein (NDSP) or C1ORF76, was newly found on chromosome 1q25.2. Previous studies of FAM163A focused on its expression and function in neuroblastoma. However, using an online database, we found that FAM163A may predict poor prognosis in lung squamous cell carcinomas (LUSC). Therefore, the role of FAM163A plays in LUSC needs to be further clarified. PATIENTS AND METHODS: Western blots, immunofluorescence and immunohistochemistry were used to detect the effect of FAM163A on mediating cell proliferation in vitro and in vivo. Co-immunoprecipitation and immunofluorescence were utilized to evaluate the interaction and co-localization of FAM163A with 14-3-3ß and ERK. RESULTS: In this study, our data revealed that FAM163A overexpression increased the levels of ERK and p90RSK phosphorylation and promoted the expression of cyclin D1. Incorporation with U0126 reversed the effects of FAM163A overexpression. FAM163A directly interacted with both 14-3-3ß and ERK and regulated the phosphorylation of ERK by upregulating the protein level of 14-3-3ß. Immunohistochemistry results also showed that FAM163A expression significantly correlated with larger tumor size (P=0.023), TNM staging (P=0.015) and regional lymph node metastasis (P=0.016). Kaplan-Meier survival analysis implied the mean survival time of patients with positive FAM163A expression (49.72±3.97 months) was much shorter than the patients with negative FAM163A expression (63.36±3.14 months, P=0.011). CONCLUSION: In summary, the present study identified a novel mechanism that FAM163A, through binding and upregulating 14-3-3ß, facilitated ERK phosphorylation that led to an increase of cellular proliferation of LUSC cells. FAM163A may be a useful marker to predict poor prognosis of patients with LUSC.

TIMM50 promotes tumor progression via ERK signaling and predicts poor prognosis of non-small cell lung cancer patients.

TIMM50 (Translocase of the inner mitochondrial membrane 50), also called TIM50, plays an essential role in mitochondrial membrane transportation. The existing literature suggests that TIMM50 may perform as an oncogenetic protein in breast cancer. However, the molecular mechanism, especially in human non-small cell lung cancer (NSCLC), is uncertain to date. In the present study, using immunohistochemistry, we found that TIMM50 expression significantly correlated with larger tumor size (P = 0.049), advanced TNM stage (P = 0.001), positive regional lymph node metastasis (P = 0.007), and poor overall survival (P = 0.001). Proliferation and invasion assay showed that TIMM50 dramatically promoted the ability of proliferation and invasion of NSCLC cells. Subsequent Western blotting results revealed that TIMM50 enhanced the expression of Cyclin D1 and Snail, and inhibited the expression of E-cadherin. Moreover, TIMM50 facilitated the expression of phosphorylated ERK and P90RSK. Incorporation of ERK inhibitor counteracted the upregulating expression of CyclinD1, and Snail, and downregulating expression of E-cadherin expression induced by TIMM50 overexpression. In conclusion, our data indicated that TIMM50 facilitated tumor proliferation and invasion of NSCLC through enhancing phosphorylation of its downstream ERK/P90RSK signaling pathway. We speculated that TIMM50 might be a useful prognosis marker of NSCLC patients.

Zinc finger protein 668 suppresses non-small cell lung cancer invasion and migration by downregulating Snail and upregulating E-cadherin and zonula occludens-1.

Zinc finger protein 668 (ZNF668) is a recently discovered protein and its expression levels, as well as its involvement in the invasion and metastasis of non-small cell lung cancer (NSCLC), are largely unknown. In the present study, immunohistochemical analysis demonstrated that ZNF668 protein expression was decreased in lung tumors (51/167, 30.5%) compared with adjacent normal lung tissues (43/62, 69.4%; P<0.001). Subsequent statistical analysis revealed that ZNF668 expression was negatively associated with increased tumor-node-metastasis stage (P=0.019) and lymph node metastasis (P=0.002). Following ZNF668 downregulation by transfection of a ZNF668-expressing plasmid or small interfering RNA, it was demonstrated that ZNF668 inhibited the invasion and migration of NSCLC cells. Furthermore, restoration of ZNF668 expression downregulated the expression of Snail and increased the protein levels of epithelial (E-)cadherin and zonula occludens-1 (ZO-1). The results of the present study suggest that ZNF668 is downregulated in human NSCLC. Furthermore, restoration of ZNF668 expression was demonstrated to decrease the expression of Snail and increase the expression of E-cadherin and ZO-1, suppressing the invasion and migration of NSCLC cells.

ARHGEF39 promotes tumor progression via activation of Rac1/P38 MAPK/ATF2 signaling and predicts poor prognosis in non-small cell lung cancer patients.

Rho guanine nucleotide exchange factor 39 (ARHGEF39), also called C9orf100, is a new member of the Dbl-family of guanine nucleotide exchange factors. Although ARHGEF39 has been proven to regulate tumor progression in hepatocellular carcinoma, the downstream signaling pathway of ARHGEF39 and its clinical associations in non-small cell lung cancer (NSCLC) are currently unknown. In the present study, using MTT, colony formation, flow cytometry, mice xenografts, wound healing, and transwell assays, we showed that ARHGEF39 promoted tumor proliferation, migration, and invasion. Furthermore, ARHGEF39 promoted the expression of Cyclin A2, Cyclin D1, and MMP2 by activating Rac1, leading to increased phosphorylation of P38 and ATF2. Treatment with a P38 inhibitor counteracted the effect of ARHGEF39 overexpression on the increase in Cyclin A2, Cyclin D1, and MMP2 expression. Moreover, the elevated levels of p-P38 and p-ATF2 caused by ARHGEF39 overexpression could be inhibited by expression of a dominant negative Rac1 mutant (T17N). In addition, the inhibition of the expression of p-P38 and p-ATF2 by ARHGEF39 RNAi could be restored by the expression of a constitutively active Rac1 mutant (Q61L). A similar impact on cell growth and invasion was observed after ARHGEF39 overexpression combined with the P38 inhibitor, Rac1 T17N, or Rac1 Q61L. Using immunohistochemistry, ARHGEF39 expression was observed to correlate positively with larger tumor size in clinical samples from 109 cases of NSCLC (P = 0.008). The Kaplan-Meier test revealed that ARHGEF39 expression significantly affected the overall survival of patients with NSCLC (52.55 ± 6.40 months vs. 64.30 ± 5.40 months, P = 0.017). In conclusion, we identified that ARHGEF39 promotes tumor growth and invasion by activating the Rac1-P38-ATF2 signaling pathway, as well as increasing the expression of Cyclin A2, Cyclin D1, and MMP2 in NSCLC cells. ARHGEF39 may be a useful marker to predict poor prognosis of patients with NSCLC.

Lasp1 promotes malignant phenotype of non-small-cell lung cancer via inducing phosphorylation of FAK-AKT pathway.

Lasp1 (LIM and SH3 domain protein 1) promotes tumor proliferation and invasion in multiple cancer entities including non-small cell lung cancer (NSCLC). However, the molecular mechanism is uncertain to date. In the present study, using immunohistochemistry, we found that Lasp1 expression was significantly correlated with tumor size (P=0.005), advanced TNM stage (P=0.042), positive regional lymph node metastasis (P=0.034) and poor overall survival (P<0.001). Similar results were seen in patients with squamous cell lung carcinoma (P=0.003 for larger tumor size, P=0.017 for advanced TNM stage, P=0.003 for positive lymph node metastasis and P<0.001 for poor overall survival) but not in patients with lung adenocarcinoma (P>0.05). Proliferation and invasion assay showed that Lasp1 dramatically promoted the ability of proliferation and invasion of NSCLC cells. Subsequent western blot results revealed that Lasp1 promoted the expression of Cyclin A2, CyclinB1, and Snail, and inhibited the expression of E-cadherin. Lasp1 directly interacted with FAK and facilitated the expression of phosphorylated FAK (Tyr397) and AKT (Ser473). Incorporation of both FAK inhibitor and AKT inhibitor counteracted the upregulating expression of Cyclin A2, CyclinB1, and Snail, and downregulating expression of E-cadherin expression induced by Lasp1 overexpression. Interestingly, inhibition of FAK signaling pathway attenuated the phosphorylation of AKT, but inhibition of AKT signaling pathway did not affect the phosphorylation of FAK. In conclusion, Lasp1 facilitated tumor proliferation and invasion of NSCLC through directly binding to FAK and enhancing the phosphorylation of FAK (Tyr397) and AKT (Ser473). Lasp1 may be a novel therapeutic target in the treatment of NSCLC patients.

TMEM17 depresses invasion and metastasis in lung cancer cells via ERK signaling pathway.

Transmembrane protein 17(TMEM17) is a newly identified protein, its expression pattern and clinicopathological relevance is still unclear. In this study, western blot assay was performed in 20 paired lung cancer samples and found that TMEM17 protein levels were lower in lung cancer tissues than that in the corresponding normal lung tissues (p=0.010). Immunohistochemistry staining in 143 cases lung cancer specimens also showed that TMEM17 expression in lung cancer tissues were significantly lower than adjacent normal lung tissues (35.7% vs 63.2%, p<0.001). And negative TMEM17 expression was significantly associated with poor histological differentiation (p=0.027), advanced TNM stages (p=0.006), positive lymph node metastasis (p=0.002) and poor prognosis (p=0.002). After overexpressing TMEM17, levels of p-ERK and its downstream molecules, p-P90RSK and Snail, were down-regulated, while levels of Occludin and Zo-1 were up-regulated, which result in the inhibition of invasion and migration ability of lung cancer cells. The effects were reversed by the incorporation of specific ERK inhibitor PD98059. In conclusion, loss of TMEM17 correlates with the development of non-small cell lung cancer (NSCLC) and predicts adverse clinical outcome of NSCLC patients. The effect of TMEM17 on inhibiting invasion and migration may attribute to restoring Occludin and Zo-1 expression through inactivating ERK-P90RSK-Snail pathway.

Alex3 suppresses non-small cell lung cancer invasion via AKT/Slug/E-cadherin pathway.

Alex3, is a newly identified mitochondrial protein, regulates mitochondrial dynamics and is involved in neural development. However, its expression pattern and clinicopathological relevance in human tumors are still unclear. In this study, Immunohistochemistry assay was performed in 109 cases of lung cancer samples and found that Alex 3 expression in lung cancer tissues was significantly lower than adjacent normal lung tissues (28.4% vs 52.6%, p < 0.001). Sequent statistical analysis indicated that negative Alex3 expression was significantly associated with advanced tumor-node-metastasis stages (p = 0.001), positive lymph node metastasis (p = 0.005), and poor prognosis (p = 0.008). After overexpression of Alex3, levels of p-AKT and Slug were downregulated, while level of E-cadherin was upregulated, which results in the inhibition of invasion and migration ability of lung cancer cells. In conclusion, reduction of Alex3 correlates with the development of non-small cell lung cancer and predicts adverse clinical outcome of non-small cell lung cancer patients. The effect of Alex3 on inhibiting invasion and migration may attribute to upregulation of E-cadherin expression through AKT-Slug pathway inactivation.

Lasp2 enhances tumor invasion via facilitating phosphorylation of FAK and predicts poor overall survival of non-small cell lung cancer patients.

Lasp2, as well as Lasp1, is a member of the LIM-protein subfamily of the nebulin group characterized by the combined presence of LIM and SH3 domains. Lasp1 and Lasp2 are highly conserved in their LIM, nebulin-like, and SH3 domains but differ significantly at their linker regions. Lasp1 had been described as an oncogenic protein that was highly expressed in diverse cancer types and facilitated tumor proliferation, invasion, and metastasis process. However, unlike Lasp1, little is known about the functions of Lasp2. In the present study, using immunohistochemistry, we found that Lasp2 expression was significantly correlated with histological type (P = 0.012), advanced TNM stage (P = 0.024), positive regional lymph node metastasis (P = 0.035), and poor overall survival (P = 0.001). Would healing assay and transwell assay results indicated that Lasp2 promoted tumor migration and invasion in NSCLC cells. Furthermore, Lasp2 facilitated Snail expression and inhibited Zo-1. The levels of phosphorylated FAK (Tyr397 and Tyr925) were obviously increased after overexpressing Lasp2 and were downregulated by transfecting Lasp2-siRNA. FAK inhibitor counteracted upregulating Snail expression and downregulating of Zo-1 expression induced by Lasp2 overexpression. Taken together, Lasp2 may facilitate tumor migration and invasion of NSCLCs through FAK-Snail/Zo-1 signaling pathway. Lasp2 may be a potential prognostic predictor of NSCLC patients.

Noxin promotes proliferation of breast cancer cells via P38-ATF2 signaling pathway.

Noxin (also called chromosome 11 open reading frame 82 or DNA damage-induced apoptosis suppressor) is associated with anti-apoptosis and cell proliferation in response to stress signals. However, to our knowledge, the role of Noxin in regulating cell proliferation is still controversial and there are no reports of the function and clinicopathological association in breast cancer. In this study, immunohistochemistry results showed that Noxin expression was significantly correlated with advanced tumor-node-metastasis stage ( p = 0.027), positive regional lymph node metastasis ( p = 0.002), and poor overall survival ( p = 0.002). Proliferation assay results showed that Noxin obviously promoted the ability of proliferation of normal breast cells. Subsequent western blot results revealed that Cyclin D1 and Cyclin E1 were upregulated by overexpressing Noxin, whereas Cyclin D1 and Cyclin E1 were downregulated after depleting Noxin. The levels of phosphorylated P38 and activating transcription factor 2 were obviously increased after overexpressing Noxin, and their expression was downregulated accordingly by transfecting Noxin-small interfering RNA. Moreover, P38 inhibitor counteracted the elevating expression of phosphorylated activating transcription factor 2, Cyclin D1, and Cyclin E1 induced by Noxin overexpression and thereby reversed the effect of Noxin overexpression on facilitating cell growth. Taken together, our studies indicated that Noxin was overexpressed in breast cancer and its positive expression was significantly correlated with advance tumor-node-metastasis stage, positive lymph node metastasis, and poor prognosis. Noxin facilitated the expression of Cyclin D1 and Cyclin E1 through activating P38-activating transcription factor 2 signaling pathway, thus enhanced cell growth of breast cancer.

CCDC106 promotes non-small cell lung cancer cell proliferation.

Coiled-coil domain containing (CCDC) family members enhance tumor cell proliferation, and high CCDC protein levels correlate with unfavorable prognoses. Limited research demonstrated that CCDC106 may promote the degradation of p53/TP53 protein and inhibit its transactivity. The present study demonstrated that CCDC106 expression correlates with advanced TNM stage (P = 0.008), positive regional lymph node metastasis (P < 0.001), and poor overall survival (P < 0.001) in 183 non-small cell lung cancer cases. A549 and H1299 cells were selected as representative of CCDC106-low and CCDC106-high expressing cell lines, respectively. CCDC106 overexpression promoted A549 cell proliferation and xenograft tumor growth in nude mice, while siRNA-mediated CCDC106 knockdown inhibited H1299 cell proliferation. CCDC106 promoted AKT phosphorylation and upregulated the cell cycle-regulating proteins Cyclin A2 and Cyclin B1. Cell proliferation promoted by CCDC106 via Cyclin A2 and Cyclin B1 was rescued by treatment with the AKT inhibitor, LY294002. Our studies revealed that CCDC106 is associated with non-small cell lung cancer progression and unfavorable prognosis. CCDC106 enhanced Cyclin A2 and Cyclin B1 expression and promoted A549 and H1299 cell proliferation, which depended on AKT signaling. These results suggest that CCDC106 may be a novel target for lung cancer treatment.

ZNF452 facilitates tumor proliferation and invasion via activating AKT-GSK3ß signaling pathway and predicts poor prognosis of non-small cell lung cancer patients.

ZNF452 is a zinc-finger protein family member which contains an isolated SCAN (SRE-ZBP, CTfin51, AW-1 and Number 18 cDNA) zinc-finger domain. Despite the SCAN N-terminus domain is known to play a role in transcriptional regulation of genes involved in cell survival and differentiation, there are no precise cellular functions that have been assigned to ZNF452. In the present study, we found that either endogenous or exogenous ZNF452 was overexpressed in the cytoplasm of NSCLC cells and positive ratio of ZNF452 in NSCLC samples (50.8%, 93/183) was significantly higher than that in normal lung tissues (22.4%, 13/58, P<0.001). ZNF452 overexpression was correlated with advanced TNM stage (P=0.033), positive lymph node metastasis (P=0.002) and predicted poor overall survival of NSCLC patients (P<0.001). ZNF452 facilitated tumor growth, colony formation, G1-S phase arrest, migration and invasion through upregulating the levels of CyclinD1, CyclinE1, p-Rb, or Snail, and downregulating the expression of Zo-1. In nude mice xenografts, overexpressing ZNF452 also promoted tumor proliferation and metastasis. Subsequently, we found that the effect of ZNF452 on facilitating tumor proliferation and invasion was through activating its downstream AKT-GSK3ß signaling pathway. Treatment of AKT inhibitor markedly prevented the phosphorylation of AKT and GSK3ß which subsequently counteracted increasing expression of CyclinD1, CyclinE1 or Snail and restored the decreasing expression of Zo-1, as well as the upregulation of tumor proliferation and invasion, caused by ZNF452 overexpression.Taken together, the present study indicated that ZNF452 may be an upstream regulator of AKT-GSK3ß signaling pathway and facilitates proliferation and invasion of NSCLC.

Kctd20 promotes the development of non-small cell lung cancer through activating Fak/AKT pathway and predicts poor overall survival of patients.

Kctd20 (potassium channel tetramerization protein domain containing 20) is a positive regulator of Akt signaling. However, the role of Kctd20 during the course of tumorigenesis and development is unclear. Using immunohistochemistry, we demonstrated that, in non-small cell lung cancer (NSCLC) patients, Kctd20 protein expression significantly correlates with advanced TNM stage (P < 0.001), positive status for regional lymph node metastasis (P = 0.019), and poor overall survival (P = 0.013). Proliferation and invasion assays showed that Kctd20 dramatically promotes the proliferation and invasion of NSCLC cells (P = 0.007 and P < 0.001, respectively). Subsequent Western Blot and qPCR experiments revealed an upregulation of Cyclin D1 and downregulation of E-cadherin in Kctd20-overexpressing cells. After depleting Kctd20, downregulaton of Cyclin D1, and upegulation of E-cadherin was observed. After overexpressing Kctd20, the levels of phosphorylated Fak (Tyr397) and Akt (Thr308) increased, while after transfection with Kctd20-siRNA these phosporylated proteins were downregulated. Moreover, in Kctd20-overexpressing cells, treatment with an Akt inhibitor reduced expression of p-Akt and Cyclin D1, enhanced E-cadherin expression, and did not impact p-Fak levels. When Kctd20-overexpressing cells were treated with a Fak inhibitor, the same effects were seen, and the level of p-Akt was reduced. Our results suggest that Kctd20 impacts proliferation and invasion of NSCLC through enhancing Fak (Tyr397) and Akt (Thr 308) phosphorylation. Kctd20 may predict prognosis and be targeted therapeutically in NSCLC.

Cytosolic THUMPD1 promotes breast cancer cells invasion and metastasis via the AKT-GSK3-Snail pathway.

Human THUMP domain-containing protein 1 (THUMPD1) is a specific adaptor protein that modulates tRNA acetylation through interaction with NAT10. Immunohistochemical analysis of 146 breast cancer specimens (82 triple-negative and 64 non-triple-negative cases) indicated THUMPD1 expression is higher in breast cancer tissues (60.9%, 89/146) than normal breast tissues (28.3%, 15/53; p < 0.001). Overall and cytosolic, but not nuclear, THUMPD1 expression in breast cancer correlated with advanced TNM stage (p = 0.003 and p < 0.001, respectively), lymph node metastasis (p = 0.001 and p < 0.001, respectively), and poor patient prognosis (p = 0.001 and p < 0.001, respectively). THUMPD1 interacted and co-localized with YAP, but did not affect Hippo pathway activity. THUMPD1 overexpression enhanced breast cancer cells invasion and migration in vivo and in vitro, possibly through activation of AKT, GSK3ß and Snail, and inhibition of E-cadherin. Treatment with the AKT inhibitor, LY294002, reduced the effects of THUMPD1 overexpression in breast cancer cells. These results indicate that THUMPD1 promotes breast cancer cells invasion and migration via the AKT-GSK3ß-Snail pathway.

DDIAS promotes invasion and proliferation of non-small cell lung cancer and predicts poor survival of lung cancer patients.

DNA damage-induced apoptosis suppressor (DDIAS), also called hNoxin or C11 or f82, is an anti-apoptotic protein in response to stress. The clinicopathological significance of DDIAS in non-small cell lung cancer patients is largely unknown until now. The purpose of our study is to analyze the clinicopathological association of DDIAS in NSCLC patients. We found that the positive ratio of DDIAS was significantly higher than that in the corresponding non-cancerous lung tissues (P<0.001). Positive DDIAS expression correlated with larger tumor size and positive regional lymph node metastasis (P=0.048 and P=0.018, respectively). Online Kaplan-Meier Plotter tool analysis results and survival analysis results of our cohort revealed that both DDIAS gene level (P=0.0048) and protein level (P<0.001) were associated with adverse outcome in NSCLC patients for overall survival, as well as in multiple subgroups divided by different clinicopathological features. Subsequent univariate and multivariate analysis suggested that only positive DDIAS was an independent prognostic factor for overall survival (P=0.018). In NSCLC cell lines, overexpression of DDIAS enhanced the ability of invasion and proliferation, whereas depleting DDIAS depressed the ability of invasion and proliferation. In conclusion, our results suggest that positive DDIAS expression may be a potent prognostic factor in NSCLC patients. DDIAS promotes proliferation and invasion in NSCLC cells and correlates with progression of NSCLC patients.