Clinical application of bronchoalveolar lavage fluid metagenomics next-generation sequencing in cancer patients with severe pneumonia.

OBJECTIVE: Metagenomic next-generation sequencing (mNGS), as an emerging technique for pathogen detection, has been widely used in clinic. However, reports on the application of mNGS in cancer patients with severe pneumonia remain limited. This study aims to evaluate the diagnostic performance of bronchoalveolar lavage fluid (BALF) mNGS in cancer patients complicated with severe pneumonia. METHODS: A total of 62 cancer patients with severe pneumonia simultaneously received culture and mNGS of BALF were enrolled in this study. We systematically analyzed the diagnostic significance of BALF mNGS. Subsequently, optimization of anti-infective therapy based on the distribution of pathogens obtained from BALF mNGS was also assessed. RESULTS: For bacteria and fungi, the positive detection rate of mNGS was significantly higher than culture method (91.94% versus 51.61%, P < 0.001), especially for poly-microbial infections (70.97% versus 12.90%, P < 0.001). Compared with the culture method, mNGS exhibited a diagnostic sensitivity of 100% and a specificity of 16.67%, with the positive predictive value (PPV) and negative predictive value (NPV) being 56.14% and 100%, respectively. The agreement rate between these two methods was 59.68%, whereas kappa consensus analysis indicated a poor concordance (kappa = 0.171). After receipt of BALF mNGS results, anti-infective treatment strategies in 39 out of 62 cases (62.90%) were optimized. Moreover, anti-tumor therapy was a high-risk factor for mixed infections (87.18% versus 65.22%, P = 0.04). CONCLUSIONS: The present study showed that cancer patients with severe pneumonia, especially those received anti-tumor therapy, were more likely to have poly-microbial infections. BALF mNGS can provide a rapid and comprehensive pathogen distribution of pulmonary infection, making it a promising technique in clinical practice, especially for optimizing therapeutic strategies for cancer patients.

Controlling the sidewall verticality of a CVD diamond in Gaussian laser grooving.

For the specific energy distribution of Gaussian laser, the obtained grooves always fall short in the sidewall verticality. To overcome this problem, the improvement of sidewall inclination in laser grooving of a CVD diamond is undertaken by the surface tilting motion control, where the insufficient material removal at the groove sidewall is relieved. Combined with finite element modelling, the influence of laser energy density, scanning speed, scanning times and scanning pitch on the inclination of sidewall are firstly analyzed, which shows that laser energy density is the main factor that dominates the sidewall inclination. The finite element simulation model (FEM) is established to achieve the contour evolution of the machining area under different tilted angles, where the generation mechanism of 'V' shape or 'W' shape at the bottom of the groove is analyzed. Finally, the inclination degree of the groove sidewall can be effectively controlled by optimizing the relative incident angle under the selected laser energy density.

Long non-coding RNAs in lung cancer: implications for lineage plasticity-mediated TKI resistance.

The efficacy of targeted therapy in non-small-cell lung cancer (NSCLC) has been impeded by various mechanisms of resistance. Besides the mutations in targeted oncogenes, reversible lineage plasticity has recently considered to play a role in the development of tyrosine kinase inhibitors (TKI) resistance in NSCLC. Lineage plasticity enables cells to transfer from one committed developmental pathway to another, and has been a trigger of tumor adaptation to adverse microenvironment conditions including exposure to various therapies. More importantly, besides somatic mutation, lineage plasticity has also been proposed as another source of intratumoural heterogeneity. Lineage plasticity can drive NSCLC cells to a new cell identity which no longer depends on the drug-targeted pathway. Histological transformation and epithelial-mesenchymal transition are two well-known pathways of lineage plasticity-mediated TKI resistance in NSCLC. In the last decade, increased re-biopsy practice upon disease recurrence has increased the recognition of lineage plasticity induced resistance in NSCLC and has improved our understanding of the underlying biology. Long non-coding RNAs (lncRNAs), the dark matter of the genome, are capable of regulating variant malignant processes of NSCLC like the invisible hands. Recent evidence suggests that lncRNAs are involved in TKI resistance in NSCLC, particularly in lineage plasticity-mediated resistance. In this review, we summarize the mechanisms of lncRNAs in regulating lineage plasticity and TKI resistance in NSCLC. We also discuss how understanding these themes can alter therapeutic strategies, including combination therapy approaches to overcome TKI resistance.

A novel 4-gene signature for overall survival prediction in lung adenocarcinoma patients with lymph node metastasis.

BACKGROUND: Lung adenocarcinoma (LUAD) patients experiencing lymph node metastasis (LNM) always exhibit poor clinical outcomes. A biomarker or gene signature that could predict survival in these patients would have a substantial clinical impact, allowing for earlier detection of mortality risk and for individualized therapy. METHODS: With the aim to identify a novel mRNA signature associated with overall survival, we analysed LUAD patients with LNM extracted from The Cancer Genome Atlas (TCGA). LASSO Cox regression was applied to build the prediction model. An external cohort was applied to validate the prediction model. RESULTS: We identified a 4-gene signature that could effectively stratify a high-risk subset of these patients, and time-dependent receiver operating characteristic (tROC) analysis indicated that the signature had a powerful predictive ability. Gene Set Enrichment Analysis (GSEA) showed that the high-risk subset was mainly associated with important cancer-related hallmarks. Moreover, a predictive nomogram was established based on the signature integrated with clinicopathological features. Lastly, the signature was validated by an external cohort from Gene Expression Omnibus (GEO). CONCLUSION: In summary, we developed a robust mRNA signature as an independent factor to effectively classify LUAD patients with LNM into low- and high-risk groups, which might provide a basis for personalized treatments for these patients.

A clinical, biologic and mechanistic analysis of the role of ZNF692 in cervical cancer.

OBJECTIVE: Cervical cancer (CC) is the most common malignancy in women. The zinc finger protein 692 (ZNF692) has been identified as a transcription factor and its aberrant expression participates in tumorigenesis of various cancers. However, its biological function and molecular mechanisms in cervical cancer remain unclear. METHODS: Microarrays were analysed by immunohistochemistry (IHC) to investigate the expression of ZNF692 in cervical cancer and its relationship with clinicopathologic characteristics. siRNAs and expression plasmids were used to reveal the biological function of ZNF692 in CC and subcutaneous xenograft model to examine the role of ZNF692 in vivo. Chromatin Immunoprecipitation and luciferase reporter assay were performed to ascertain whether ZNF692 binds to the promoter region of p27kip1. RESULTS: By analyzing The Cancer Genome Atlas (TCGA) dataset, we confirmed ZNF692 as a potential oncogene in CC. ZNF692 expression was up-regulated in CC tissues compared with that in adjacent normal tissues, and its overexpression was correlated with poor clinicopathologic characteristics. Moreover, ZNF692 promoted the proliferation, migration and invasion of CC cells both in vitro and in vivo. Regarding molecular mechanisms, up-regulation of ZNF692 was found to enhance the G1/S transition via regulating the p27kip1/PThr160-CDK2 signal pathway in CC cells. CONCLUSION: ZNF692 promotes CC cells proliferation and invasion through suppressing p27kip1 transcription by directly binding its promoter region, which suggests that ZNF692 may serve as an underlying therapeutic target and prognostic marker in CC.

ZNF692 promotes proliferation and cell mobility in lung adenocarcinoma.

By analyzing The Cancer Genome Atlas (TCGA) datasets, we discovered that the zinc finger protein 692 (ZNF692) were over-expressed in Lung adenocarcinoma (LUAD) tissues compared to adjacent non-tumor tissues (P < 0.0001). In this study, we investigated the function of ZNF692 in the progression of LUAD. We found that ZNF692 knockdown inhibited LUAD cells proliferation, migration, and invasion both in vitro and in vivo. And LUAD cell apoptosis was induced following the down-regulation of ZNF692. Our results show that ZNF692 is over-expressed in LUAD tissues compared to adjacent normal tissues, and hyper-expression of ZNF692 in LUAD is an independent risk factor for worse overall survival in LUAD patients (HR: 8.800, 95%CI: 1.082-71.560, P = 0.042) by Tissue Microarray stain assay (TMA). GO analysis indicated that most genes were enriched in metabolic process which were associated highly with ZNF692 levels. Collectively, our results suggested that ZNF692 may serve as a potential oncogene and biomarker in LUAD by influencing cell metabolism.

[Secondary Metabolites from Penicillium raistrickii].

OBJECTIVE: To investigate the secondary metabolites from Penicillium raistrickii. METHODS: Compounds were isolated and purified by normal and reverse phase silica gel, Sephadex LH-20 gel column chromatography and RP-HPLC. Their structures were established by means of spectral techniques and physicochemical properties. RESULTS: Twelve compounds were identified as pestafolide A(II), 3-methoxy-4-methyl-2,4-dien-pentanoic acid (2),p-hydroxy phenylacetamide (3),2-(2-hydroxy propanamido) benzamide (4), nicotinic acid (5), thymine (6), uracil (7) cyclo (Gly-Ala) (8), (22E,24R)-3ß,5α,9α-trihydroxy ergosta-7,22-diene-6-one (9), cerevisterol (10), ergosterol (11) and ergosterol peroxide (12). CONCLUSION: All compounds are isolated from Penicillium raistrickii for the first time.

ITPR1-AS1 promotes small cell lung cancer metastasis by facilitating P21HRAS splicing and stabilizing DDX3X to activate the cRaf-MEK-ERK cascade.

The mechanisms underlying the involvement of long non-coding RNAs (lncRNAs) in the metastasis of small cell lung cancer (SCLC) remain largely unknown. Here, we identified that the lncRNA ITPR1-AS1 was upregulated in SCLC and lymph node metastasis tissues and positively correlated with SCLC malignant features. The overexpression of ITPR1-AS1 in SCLC was an independent risk factor for the overall survival of patients with SCLC. Our data confirmed that ITPR1-AS1 induces SCLC cell metastasis both in vitro and in vivo. Mechanistically, ITPR1-AS1 acts as a scaffold to enhance the interaction between SRC-associated in mitosis 68 kDa and heterogeneous nuclear ribonucleoprotein A1, which facilitates the alternative splicing of the H-Ras proto-oncogene (HRAS) pre-mRNA (P21HRAS). Moreover, we observed that ITPR1-AS1 could associate in a complex with and maintain the stability of DEAD-box polypeptide 3 (DDX3X), which inhibited the latter's ubiquitination and degradation. Our data provide evidence that ITPR1-AS1 activates the cRaf-MEK-ERK cascade by upregulating P21HRAS production and stabilizing DDX3X, to promote SCLC metastasis.

Cross-Sectional Profile Evolution of Cu-Ti Gradient Films on C17200 Cu by Vacuum Thermal Diffusion.

To improve the wear resistance and fatigue life of Cu alloys, surface modification by combining the magnetron sputtering of Ti film followed by vacuum thermal diffusion is always applied, where the structure and composition of the fabricated film play a determinant role on the mechanical properties. In the present work, the evolution of the layered structure and the element distribution of the formed multi-phases coating on C17200 Cu alloy are investigated by mathematical calculation based on Fick's law, and the experimental verification by the thermal diffusion of the gradient Cu-Ti film was undertaken under different temperatures and durations. The results show that the layered structure of the fabricated coating is dependent on the Cu-Ti atom concentration, the increasing time and the temperature, where a single or stratified layer is formed due to the generated Cu-Ti intermetallics for the inter-diffusion between the Cu and Ti atoms. The atom distribution by the proposed simulation method based on Fick's law corresponds to the experimental results, which can be applied to designing the structure of the modification layer.

Sulfonylurea receptor 1-expressing cancer cells induce cancer-associated fibroblasts to promote non-small cell lung cancer progression.

Cancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression; however, how CAFs are induced remains elusive. Sulfonylurea receptor 1 (SUR1) is a tumor-enhancer in non-small cell lung carcinoma (NSCLC). Here, we probed the influence of SUR1-expressing cancer cells on CAFs. Results showed that high SUR1 expression positively correlated with α-SMA positive staining of CAFs in tumor tissues and poor prognosis of NSCLC patients. SUR1 contributed to normal fibroblast (NF) transformation into CAFs and facilitated the growth and metastasis of NSCLC in vivo. Conditioned medium (CM) and exosomes from SUR1-expressing cancer cells induced CAFs and promoted fibroblast migration. In cancer cells, SUR1 promoted p70S6K-induced KH-type splicing regulatory protein (KHSRP) phosphorylation at S395 to inhibit the binding of KHSRP with let-7a precursor (pre-let-7a) and decreasing mature let-7a-5p expression in cancer cells and exosomes. Let-7a-5p delivered by exosomes blocked NF transformation into CAFs by targeting TGFBR1 to inactivate the TGF-ß signaling pathway. Glibenclamide, which targets SUR1, restrained CAFs and suppressed tumor growth in patient-derived xenograft models. Furthermore, we found that let-7a-5p was decreased in the tissues and plasma exosomes of NSCLC patients. In summary, SUR1-expressing cancer cells induce NF transformation into CAFs in the tumor microenvironment and promote NSCLC progression by transferring less exosomal let-7a-5p. Glibenclamide is a promising anti-cancer drug, and plasma exosomal let-7a-5p level is a potential diagnostic biomarker for NSCLC patients. These findings provide new therapeutic strategies by targeting SUR1 in NSCLC.

Meiotic nuclear divisions 1 (MND1) fuels cell cycle progression by activating a KLF6/E2F1 positive feedback loop in lung adenocarcinoma.

BACKGROUND: Considering the increase in the proportion of lung adenocarcinoma (LUAD) cases among all lung cancers and its considerable contribution to cancer-related deaths worldwide, we sought to identify novel oncogenes to provide potential targets and facilitate a better understanding of the malignant progression of LUAD. METHODS: The results from the screening of transcriptome and survival analyses according to the integrated Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) data were combined, and a promising risk biomarker called meiotic nuclear divisions 1 (MND1) was selectively acquired. Cell viability assays and subcutaneous xenograft models were used to validate the oncogenic role of MND1 in LUAD cell proliferation and tumor growth. A series of assays, including mass spectrometry, co-immunoprecipitation (Co-IP), and chromatin immunoprecipitation (ChIP), were performed to explore the underlying mechanism. RESULTS: MND1 up-regulation was identified to be an independent risk factor for overall survival in LUAD patients evaluated by both tissue microarray staining and third party data analysis. In vivo and in vitro assays showed that MND1 promoted LUAD cell proliferation by regulating cell cycle. The results of the Co-IP, ChIP and dual-luciferase reporter assays validated that MND1 competitively bound to tumor suppressor Kruppel-like factor 6 (KLF6), and thereby protecting E2F transcription factor 1 (E2F1) from KLF6-induced transcriptional repression. Luciferase reporter and ChIP assays found that E2F1 activated MND1 transcription by binding to its promoter in a feedback manner. CONCLUSIONS: MND1, KLF6, and E2F1 form a positive feedback loop to regulate cell cycle and confer DDP resistance in LUAD. MND1 is crucial for malignant progression and may be a potential therapeutic target in LUAD patients.

Identification of LBX2 as a novel causal gene of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most predominant histological type of lung cancer with a poor prognosis. In this study, we demonstrate that LBX2 regulates cell proliferation, migration and invasion and the potential molecular mechanism in LUAD. METHODS: The Cancer Genome Atlas dataset was accessed to screen for novel genes and immunohistochemistry (IHC) assays were performed to determine the association between LBX2 expression and clinicopathological features of LUAD. 5-ethynyl-2'-deoxyuridine, colony formation and Real Time xCELLigence analysis system were used to evaluate the cell proliferation abilities of LUAD. Wound healing, transwell and Matrigel assays were used to detect cell migration and invasion capacities. Xenograft tumor models were used to assess the oncogenic role of LBX2 in vivo. RESULTS: We found that LBX2 was hyperexpressed in LUAD and correlated with clinicopathological features and poor prognosis in LUAD patients. Knockdown of LBX2 inhibited cell proliferation, migration and invasion of LUAD, whereas ectopic expression of LBX2 enhanced tumor growth, migration, and invasion. We further found that LBX2 might participate in epithelial-to-mesenchymal transition (EMT) progression and influence EMT-related gene expression. CONCLUSIONS: The current study suggests that LBX2 plays an oncogenic role in LUAD and may participate in tumor proliferation, migration, and invasion through EMT progression. KEY POINTS: Significant findings of the study LBX2 might participate in LUAD cell proliferation, migration and invasion via EMT progression. What this study adds LBX2 may represent a potential biomarker and a promising therapeutic target for LUAD.

MNX1 Promotes Malignant Progression of Cervical Cancer via Repressing the Transcription of p21cip1.

Motor neuron and pancreas homeobox 1 (MNX1) is a development-related genes and has been found to be highly expressed in several cancers. However, its biological function in cervical cancer remains largely unexplored. QRT-PCR, western blot, and IHC showed that MNX1 was abnormally overexpressed in cervical cancer tissues and cell lines. The high expression level of MNX1 correlated with poorer clinicopathologic characteristics in cervical cancer patients. Evaluated by RTCA (Real Time Cellular Analysis) proliferation assay, colony formation assay, EdU assay, transwell assay, and matrigel assay, we found that knockdown of MNX1 inhibited proliferation, migration and invasion of cervical cancer in vitro, while overexpression of MNX1 promoted malignant phenotype of cervical cancer. And subcutaneous xenograft model confirmed the malignant phenotype of MNX1 in vivo. Furthermore, flow cytometry, chromatin immunoprecipitation, and luciferase reporter assay indicated that MNX1 accelerated cell cycle transition by transcriptionally downregulating cyclin-dependent kinases p21cip1. In summary, our study revealed that MNX1 exerted an oncogenic role in cervical cancer via repressing the transcription of p21cip1 and thus accelerating cell cycle progression. Our results suggested that MNX1 was a potential diagnostic marker and therapeutic target for cervical cancer patients.

Simulation and Experimental Study on the Surface Generation Mechanism of Cu Alloys in Ultra-Precision Diamond Turning.

The surface generation mechanism of the Cu alloys in ultra-precision diamond turning is investigated by both simulation and experimental methods, where the effects of the cutting parameters on the surface characteristics are explored, including the workpiece spindle speed, the cutting depth, the feed rate and the nose radius of the diamond tool. To verify the built model, the cutting experiments are conducted at selected parameters, where the causes of the error between the simulation and the machining results are analyzed, including the effects of the materials microstructure and the diamond tool wear. In addition, the nanometric surface characteristics of the Cu alloys after the diamond turning are identified, including the finer scratching grooves caused by the tool wear, the formation of the surface burs and the adhesion of graphite. The results show that the built model can be basically used to predict the surface topography for the selection of the appropriate machining parameters in the ultra-precision diamond turning process.

DMBX1 promotes tumor proliferation and regulates cell cycle progression via repressing OTX2-mediated transcription of p21 in lung adenocarcinoma cell.

Lung adenocarcinoma (LUAD) was the predominant histological subtype of lung cancer, with poor prognosis. By analyzing the TCGA dataset, we found that DMBX1 (diencephalon/mesencephalon homeobox 1), a member of the bicoid sub-family of homeodomain-containing transcription factors, was overexpressed in LUAD and correlated with poorer prognosis and more advanced clinicopathological features of LUAD patients. Silencing of DMBX1 inhibited proliferation of LUAD and induced G1/S cell cycle arrest, whereas ectopic expression of DMBX1 enhanced tumor growth of LUAD and promoted G1/S cell cycle exit. Furtherly we found that the function of DMBX1 was dependent on p21 (CDKN1A), a key regulator of G1/S cell cycle progression. Co-IP assay revealed that DMBX1 directly bound to another homeobox transcription factor, OTX2. ChIP and luciferase reporter assay confirmed that OTX2 directly interacted with the promoter region of p21 to enhance its transcription, and DMBX1 repressed OTX2-mediated transcription of p21. Our study reveals that DMBX1 plays an oncogenic role in LUAD by repressing OTX2-mediated transcription of p21 and the results may provide new therapeutic targets for LUAD patients.

Porous coordination/covalent hybridized polymers synthesized from pyridine-zinc coordination compound and their CO2 capture ability, fluorescence and selective response properties.

Currently, porous polymers are mainly synthesized by linking coordination or organic covalent bonds. In this study, we propose the synthesis of a porous coordination/covalent hybridized polymer from di(4-vinylpyridine)-dichloro-zinc (ZnVP2) by "coordination-polymerization" method. The resulting porous polymer demonstrated CO2 capture ability and multi-responsive properties.

SNAP23 suppresses cervical cancer progression via modulating the cell cycle.

OBJECTIVE: Cervical cancer (CC) is one of the most common gynecologic tumors in women worldwide, with poor prognosis and low survival rate. In this study, we identified SNAP23 as a potential tumor suppressor gene in CC. METHODS: The expression of SNAP23 in tissues and cell lines were measured by qRT-PCR, western blot and IHC. Knockdown of SNAP23 by siRNA and ectopic expression of SNAP23 by overexpression plasmid were performed to observe the biological function of SNAP23 in CC. Xenograft nude mice models were established to measure its function in vivo. RESULTS: SNAP23 was downregulated in CC tissues and had a negative correlation with advanced clinical characteristics. Ectopic expression of SNAP23 suppressed malignant phonotype of CC while knockdown of SNAP23 promoted the progression of CC in vitro. The flow cytometry analysis revealed that SNAP23 exerted its tumor suppressor activity via inducing G2/M cell cycle arrest. Moreover, xenograft tumor models showed that SNAP23 suppresses tumor growth in vivo. CONCLUSIONS: Our results revealed that SNAP23 suppressed progression of CC and induced cell cycle G2/M arrest via upregulating p21cip1 and downregulating CyclinB1.

Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients.

OBJECTIVE: Hypomyelinating disorders are a group of clinically and genetically heterogeneous diseases characterized by neurological deterioration with hypomyelination visible on brain MRI scans. This study was aimed to clarify the clinical and genetic features of HMDs in Chinese population. METHODS: 119 patients with hypomyelinating disorders in Chinese population were enrolled and evaluated based on their history, clinical manifestation, laboratory examinations, series of brain MRI with follow-up, genetic etiological tests including chromosomal analysis, multiplex ligation probe amplification, Sanger sequencing, targeted enrichment-based next-generation sequencing and whole exome sequencing. RESULTS: Clinical and genetic features of hypomyelinating disorders were revealed. Nine different hypomyelinating disorders were identified in 119 patients: Pelizaeus-Merzbacher disease (94, 79%), Pelizaeus-Merzbacher-like disease (10, 8%), hypomyelination with atrophy of the basal ganglia and cerebellum (3, 3%), GM1 gangliosidosis (5, 4%), GM2 gangliosidosis (3, 3%), trichothiodystrophy (1, 1%), Pol III-related leukodystrophy (1, 1%), hypomyelinating leukodystrophy type 9 (1, 1%), and chromosome 18q deletion syndrome (1, 1%). Of the sample, 94% (112/119) of the patients were genetically diagnosed, including 111 with mutations distributing across 9 genes including PLP1, GJC2, TUBB4A, GLB1, HEXA, HEXB, ERCC2, POLR3A, and RARS and 1 with mosaic chromosomal change of 46, XX,del(18)(q21.3)/46,XX,r(18)(p11.32q21.3)/45,XX,-18. Eighteen novel mutations were discovered. Mutations in POLR3A and RARS were first identified in Chinese patients with Pol III-related leukodystrophy and hypomyelinating leukodystrophy, respectively. SIGNIFICANCE: This is the first report on clinical and genetic features of hypomyelinating disorders with a large sample of patients in Chinese population, identifying 18 novel mutations especially mutations in POLR3A and RARS in Chinese patients, expanding clinical and genetic spectrums of hypomyelinating disorders.

SNAP23 promotes the malignant process of ovarian cancer.

BACKGROUND: Ovarian cancer (OC) was the primary malignant gynecological cancer and SNARE protein is closely related with tumor progression. Here, we identified SNAP23, a member of SNARE complex, as a potential oncogene in OC. METHODS: We determined the expression of SNAP23 in OC tissues and explored the clinical significance through bioinformatics analysis. The effects of SNAP23 on OC cell proliferation, migration, invasion, cell cycle and apoptosis were then evaluated in vitro. RESULTS: SNAP23 is hyper-expressed in OC tumor tissues compared to normal tissues, and increased expression of SNAP23 is associated with a poor progression free survival (HR = 1.24, 95% CI = 1.07-1.44, p = 0.0042). SNAP23 knock down increases cell apoptosis and inhibits cell proliferation, migration and invasion of OC cells. GO analysis reveals that most genes correlated highly with SNAP23 were enriched in metabolic process. CONCLUSIONS: Our data suggest that SNAP23 may serve as an oncogene promoting tumorigenicity of OC cells by decreasing apoptotic process.

Upregulation of FAM83D promotes malignant phenotypes of lung adenocarcinoma by regulating cell cycle.

The family with sequence similarity 83, member D (FAM83D) gene is upregulated in hepatocellular carcinoma and ovarian cancer, and its overexpression has been reported to positively correlate with tumor progression. However, the clinical significance and biological function of FAM83D in lung adenocarcinoma has not been investigated. We determined the expression profile and clinical significance of FAM83D using The Cancer Genome Atlas (TCGA) and immunohistochemistry (IHC) analysis. Considerable upregulation of FAM83D was observed in LUAD tissues compared with adjacent normal tissues, and its overexpression was significantly associated with more advanced clinicopathological characteristics. Importantly, multivariate Cox regression analysis indicated that a high level of FAM83D expression was an independent risk factor for worse overall survival in LUAD patients (HR = 1.692, P = 0.006). Inhibition of FAM83D suppressed the proliferation of LUAD cells via G1 phase arrest by downregulating cyclin D1 (CCND1) and cyclin E1 (CCNE1). The oncogenic role of FAM83D was also confirmed in vivo. In conclusion, our study demonstrated that FAM83D might exert its oncogenic activity in LUAD by regulating cell cycle, and that it could serve as a novel biomarker and a potential therapeutic target for LUAD.