Inhibition of HIST1H2AB suppresses the proliferation of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is one of the common causes of cancer-related deaths worldwide. Histone cluster 1 H2A family member b (HIST1H2AB) is a member of the histone H2A family. Bioinformatic analyses have revealed that HIST1H2AB is highly expressed in some cancers and might be an oncogene. However, information on the function of HIST1H2AB in lung adenocarcinoma is limited. METHODS: The expression of HIST1H2AB was analyzed in normal lung, lung adenocarcinoma and paracancerous tissues from The Cancer Genome Atlas (TCGA) database and immunohistochemistry staining. It was further verified in the relative cell lines using real-time quantitative polymerase chain reaction (RT-qPCR). When the adenocarcinoma cells lines (A549 and H1299) were successfully transfected with shHIST1H2AB or an empty plasmid packaged into a lentivirus, cell proliferation was detected using Celigo fluorescence cell-counting, colony formation and annexin V-allophycocyanin assays. Twenty nude mice were subcutaneously injected with A549 cells transfected with shHIST1H2AB or empty plasmid; the tumor size was recorded on day 25 and then measured every 3 days thereafter. The final tumor weight was measured on day 37. Significantly differentially expressed genes were analyzed using a human gene expression array. Furthermore, the potentially relevant genes were verified using RT-qPCR and western blotting. RESULTS: HIST1H2AB was highly expressed in lung adenocarcinoma tissues from TCGA database and immunohistochemistry staining. Similar results were seen in the lung adenocarcinoma cells. When the cells were successfully transfected with shHIST1H2AB or an empty plasmid, downregulation of HIST1H2AB inhibited the growth and promoted the apoptosis of lung adenocarcinoma cells. The xenograft results suggested that HIST1H2AB downregulation delayed tumor growth and reduced tumor weight. Moreover, interferon signaling pathway and four genes (HMGB1, FOXM1, F2RL1 and SLC4A7) might be regulated by HIST1H2AB in the development of lung adenocarcinoma as indicated through gene expression array, RT-qPCR and western blotting analyses. CONCLUSIONS: HIST1H2AB acts as an oncogenic protein and HIST1H2AB inhibition suppresses the proliferation of lung adenocarcinoma cells. It may be a novel target for lung adenocarcinoma therapy.

First-line crizotinib therapy is effective for a novel SEC31A-anaplastic lymphoma kinase fusion in a patient with stage IV lung adenocarcinoma: a case report and literature reviews.

Anaplastic lymphoma kinase (ALK) fusion was found in 3-7% of all patients with nonsmall cell lung cancer. The efficacy of ALK-tyrosine kinase inhibitor (ALK-TKI) in EML4-ALK has been extensively studied, whereas little evidence is available on its efficacy in rare ALK fusions. Here, we report the performance of crizotinib in a 50-year-old male lung adenocarcinoma patient with a novel rare SEC31A-ALK fusion. Computed tomography (CT) scan revealed multiple patchy high-density shadows in both lungs. The larger ones are located near the spine in the right lung lower lobe (55 × 34 mm) and the left hilar region (45 × 26 mm), with multiple enlarged mediastinal and axillary lymph nodes. Biopsy by bronchoscopy revealed invasive adenocarcinoma. The pathological stage of T4N3M1b (clinical stage: IVA) was confirmed. Next-generation sequencing revealed SEC31A: exon20~ALK: exon20 fusion, ABCB1 amplification, FGF19 amplification, DAXX p.S213L, MUTYH p.R19*(germline mutation and pathogenic) with tumor mutational burden at 3.2 mutations/Mb, microsatellite stable, proficient mismatch repair and PD-L1 positive [immunohistochemistry, tumor proportion score(TPS) 1-49% (TPS = 25%)]. Based on these findings, crizotinib was recommended for the first-line treatment at 250 mg twice daily. The first CT assessment after 2-month therapy showed partial response (PR) for the two larger lesions, multiple shadows and nodules in both lungs and the mediastinal and axillary lymph nodes. Crizotinib at 250 mg twice a day was applied in the following 9 months. Assessment at every 3 months (up to 1-year after diagnosis) showed further absorption for all lesions (continuous PR). We reported a novel rare ALK fusion SEC31A: EXON20~ALK: exon20 and showed the effectiveness of crizotinib against the fusion. This study provided strong evidence for the efficacy of ALK-TKI for rare ALK fusion.

Inhibition of AHNAK nucleoprotein 2 alleviates pulmonary fibrosis by downregulating the TGF-ß1/Smad3 signaling pathway.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and advanced interstitial lung disease with poor prognosis. AHNAK nucleoprotein 2 (AHNAK2) is a macromolecular protein that is important for cell migration and muscle membrane repair. The protein acts via epithelial-mesenchymal transition (EMT), which is a key mechanism in the pathogenesis of IPF. However, very few studies have elucidated the effect of AHNAK2 in the development of IPF. Therefore, we aimed to determine the role of AHNAK2 in IPF development. METHODS: C57BL/6 mice were induced with bleomycin, while A549 and Beas-2b pulmonary epithelial cell lines were treated with TGF-ß1 to induce IPF model. The expression of AHNAK2 was detected using immunohistochemistry staining in vivo, and real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) in vitro. C57BL/6 mice were injected with adeno-associated virus (AAV)-sh NC or AAV-sh AHNAK2 and the pulmonary function and EMT marker expression were measured. The migratory abilities of the two transforming growth factor beta 1 (TGF-ß1)-induced cell lines were examined using wound-healing and Transwell assays after transfection with si-NC, si-AHNAK2-1 and -2. EMT marker expression was detected using RT-qPCR and WB. Smad3 and phosphorylated-Smad3 of the two cells were examined using WB. Following Smad3 inhibition by Smad3 phosphorylation inhibitor (SIS3), TGF-ß1-induced cell migration and EMT marker expression were evaluated again after different transfections. RESULTS: AHNAK2 expression was higher in the IPF model than in the normal model in vivo and in vitro. Partial inhibition of AHNAK2 suppressed the EMT process and improved pulmonary ventilation and compliance in the mouse model of IPF. Similarly, knockdown of AHNAK2 suppressed the migration of pulmonary epithelial cells and reversed EMT. Furthermore, Smad3 of the two TGF-ß1-induced cell lines was not activated when AHNAK2 was inhibited. When SIS3 inhibited the activation of Smad3, the suppression of AHNAK2 had no effect on A549 and Beas-2b, regardless of TGF-ß1 induction. CONCLUSIONS: Inhibition of AHNAK2 alleviates pulmonary fibrosis and partially reverses EMT by inhibiting the TGF-ß1/Smad3 signaling pathway. Therefore, AHNAK2 is a potential therapeutic target for IPF.

Pulmonary invasive mucinous adenocarcinoma mimicking pulmonary actinomycosis.

BACKGROUND: Primary pulmonary invasive mucinous adenocarcinoma is a rare and distinct subtype of lung adenocarcinoma. CASE PRESENTATION: A 72-year-old woman presented with productive cough for two months and fever for six days. Chest computed tomography (CT) showed a mass in the left lower lobe. Sputum culture tested negative for bacteria, but the sequence of Actinomyces meyeri was detected by metagenomic next generation sequencing from the bronchoalveolar lavage fluid. It was considered a pathogenic bacterium as the normalized number of DNA sequencing reads was 10 times higher than the normal level. The patient's symptoms alleviated quickly, and the chest CT lesion shrank to a third of the original size following treatment with penicillin for two months. However, a repeat chest CT performed after four months of treatment revealed that the lesion had expanded. Positron emission tomography/CT revealed that fluorodeoxyglucose metabolism was increased in the mass with surrounding ground glass density of the left lower lobe. Furthermore, CT-guided percutaneous lung biopsy was performed, and hematoxylin-eosin staining showed columnar tumor cells with abundant mucin in the cytoplasm with a basal nucleus. Finally, the patient was diagnosed with pulmonary invasive mucinous adenocarcinoma and agreed to undergo a thoracoscopic surgery. CONCLUSIONS: Pulmonary invasive mucinous adenocarcinoma is a subset of lung adenocarcinoma with low incidence rate. The clinical features and CT findings are non-specific. A histopathological diagnosis is of fundamental importance in preventing misdiagnosis.

Clinical exome sequencing identifies novel compound heterozygous mutations of the WEE2 gene in primary infertile women with fertilization failure.

OBJECTIVE: The genetic basis of fertilization failure after intracytoplasmic sperm injection (ICSI) is largely unknown and the aim of this study is to investigate the genetic causes of fertilization failure in primary infertile women. METHODS: Six affected women diagnosed with infertility and fertilization failure were recruited. The genetically pathogenic factor of their fertilization failures were investigated by clinical exome sequencing. One hundred healthy controls were verified by Sanger sequencing. RESULTS: Novel compound heterozygous mutations c.625G > T and c.759-2A > G of WEE2 in one affected individual were revealed by clinical exome sequencing. Trios analysis of the mutations represented an autosomal recessive pattern. The nonsense mutation c.625G > T (p.Glu209*) indicated the truncation of the WEE2 protein and c.759-2A > G was predicted to affect the splicing. CONCLUSIONS: The novel variants extend the spectrum of WEE2 mutations, which promotes the prognostic value of testing for WEE2 mutations in infertile women with fertilization failure.

Long noncoding RNA SNHG1 promotes non-small cell lung cancer progression by up-regulating MTDH via sponging miR-145-5p.

Long noncoding RNAs participate in the progression and initiation of non-small cell lung cancer (NSCLC), although the mechanism remains unknown. The lncRNA identified as small nucleolar RNA host gene 1 ( SNHG1) is a novel lncRNA that is increased in multiple human cancers; however, the regulatory mechanism requires further investigation. In this study, we discovered that SNHG1 was markedly up-regulated in NSCLC tissues and cells and that SNHG1 silencing decreased tumor volumes. Moreover, we explored its regulatory mechanism and found that SNHG1 directly bound to microRNA (miRNA)-145-5p, isolating miR-145-5p from its target gene MTDH. Inhibition of SNHG1 suppressed NSCLC cell viability, proliferation, migration, and invasion in vitro, but its effect was rescued by miR-145-5p inhibition. These results demonstrate that SNHG1 contributes to NSCLC progression by modulating the miR-145-5p/ MTDH axis, and it could potentially be a therapeutic target as well as a diagnostic marker.-Lu, Q., Shan, S., Li, Y., Zhu, D., Jin, W., Ren, T. Long noncoding RNA SNHG1 promotes non-small cell lung cancer progression by up-regulating MTDH via sponging miR-145-5p.

Epigenetic association analysis of clinical sub-phenotypes in patients with polycystic ovary syndrome (PCOS).

Polycystic ovarian syndrome (PCOS) is a complex disorder affecting up to 15-20% of reproductive women. PCOS has recently been investigated using genome-wide association studies revealing important mutations and DNA methylation sites associated with the syndrome. As a clinically highly heterogenous condition, studying the molecular basis of the differential manifestation of PCOS is both meaningful concerning individualized management and important for understanding the biology of PCOS. Using genome-wide DNA methylation data collected from PCOS patients, we performed a powerful region-based analysis to detect differentially methylated regions (DMR) by correlating DNA methylation pattern in a genomic region with the level of each PCOS clinical sub-phenotype. We identified seven significant DMRs on chromosome 19 (12877188-12876846 bp) and chromosome 6 (MHC region) associated with prolactin level, as well as chromosomes 11 and 2 associated with metabolic attributes. Functional annotation linked significant DNA methylation patterns to functional genes (HOOK2, BDNFl, HLA-G, HLA-H, HLA-J, RNF39, etc) of metabolic disorders and immunity or novel associations to serve as targets for validation and replication.

miR-34b-5p inhibition attenuates lung inflammation and apoptosis in an LPS-induced acute lung injury mouse model by targeting progranulin.

Inflammation and apoptosis play important roles in the initiation and progression of acute lung injury (ALI). Our previous study has shown that progranulin (PGRN) exerts lung protective effects during LPS-induced ALI. Here, we have investigated the potential roles of PGRN-targeting microRNAs (miRNAs) in regulating inflammation and apoptosis in ALI and have highlighted the important role of PGRN. LPS-induced lung injury and the protective roles of PGRN in ALI were first confirmed. The function of miR-34b-5p in ALI was determined by transfection of a miR-34b-5p mimic or inhibitor in intro and in vivo. The PGRN level gradually increased and subsequently significantly decreased, reaching its lowest value by 24 hr; PGRN was still elevated compared to the control. The change was accompanied by a release of inflammatory mediators and accumulation of inflammatory cells in the lungs. Using bioinformatics analysis and RT-PCR, we demonstrated that, among 12 putative miRNAs, the kinetics of the miR-34b-5p levels were closely associated with PGRN expression in the lung homogenates. The gain- and loss-of-function analysis, dual-luciferase reporter assays, and rescue experiments confirmed that PGRN was the functional target of miR-34b-5p. Intravenous injection of miR-34b-5p antagomir in vivo significantly inhibited miR-34b-5p up-regulation, reduced inflammatory cytokine release, decreased alveolar epithelial cell apoptosis, attenuated lung inflammation, and improved survival by targeting PGRN during ALI. miR-34b-5p knockdown attenuates lung inflammation and apoptosis in an LPS-induced ALI mouse model by targeting PGRN. This study shows that miR-34b-5p and PGRN may be potential targets for ALI treatments.

Lnc-SNHG1 may promote the progression of non-small cell lung cancer by acting as a sponge of miR-497.

Lnc-SNHG1 (small nucleolar RNA host gene 1) is considered an important regulating factor in several types of cancers. However, the biological functions and underlying molecular mechanisms in which lnc-SNHG1 is involved in non-small cell lung cancer (NSCLC) still need to be explored. In this study, we investigated the detailed effects and possible molecular mechanisms. The transcript level of lnc-SNHG1 was higher in lung adenocarcinoma specimens and NSCLC cell lines than in noncancer tissue and cells. The level of expression was positively correlated with invasiveness and was negatively correlated with the level of miR-497 in vivo and in vitro. In exploring the regulatory mechanism, we found that lnc-SNHG1 might modulate tumor growth by sponging miR-497. The inhibitory effect of si-lnc-SNHG1 on NSCLC cell proliferation, migration and invasion could be rescued by miR-497 inhibition, while the overexpression of miR-497 could reverse the effect of lnc-SNHG1 overexpression. Furthermore, our study demonstrated that the lnc-SNHG1 regulated the expression of the insulin-like growth factor 1 receptor (IGF1-R) by acting as a sponge of miR-497 in NSCLC. lnc-SNHG1 could be a novel biomarker as well as a curative target.

miR-145 and miR-497 suppress TGF-ß-induced epithelial-mesenchymal transition of non-small cell lung cancer by targeting MTDH.

BACKGROUND: MicroRNAs (miRNAs) have been reported to play crucial roles in multiple cancers including non-small cell lung cancer (NSCLC). Here, we investigated the role of miR-145 and miR-497 in TGF-ß-induced epithelial-mesenchymal transition (EMT) process of NSCLC. METHODS: We performed quantitative real time PCR (qRT-PCR) to detect the expression level of miR-145 and miR-497 in NSCLC cell lines. Then in the presence/absence of TGF-ß, we transfected miRNA mimics or inhibitor into A549 and H1299 cells and investigated the role of miR-145 and miR-497 in cell migration and invasion using transwell and wound-healing assay. The regulation role of miR-145 and miR-497 on Metadherin (MTDH) was determined by luciferase assay. The expression level of MTDH and EMT markers E-cadherin and vimentin were detected on mRNA and protein level. RESULTS: In our study, our results showed that miR-145 and miR-497 were downregulated in NSCLC cell lines. Overexpression of miR-145 and miR-497 inhibited TGF-ß-induced EMT and suppressed cancer cell migration and invasion, while the opposite results were observed in cells transfected with miR-145 or miR-497 inhibitor. Moreover, the luciferase assay confirmed that miR-145 and miR-497 attenuated MTDH expression by directly binding 3'-UTR of MTDH mRNA and exert the tumor-suppression role. CONCLUSIONS: Overall, we demonstrated that miR-145 and miR-497 functioned as EMT-suppressor in NSCLC by targeting MTDH, provided new evidence that miR-145 and miR-497 as potential therapeutic targets.

The epigenomics of polycystic ovarian syndrome: from pathogenesis to clinical manifestations.

Polycystic ovarian syndrome (PCOS) is a complex condition of ovarian dysfunction and metabolic abnormalities with widely varying clinical manifestations resulting from interference of the genome and the environment through integrative biological mechanisms with the emerging field of epigenetics offering an appealing tool for studying the nature and nurture of the disease. We review the current literature of epigenetic studies on PCOS from disease development to the association analysis of the DNA methylome and to exploratory studies on the molecular mechanisms of disease heterogeneity and comorbidity. Recent data based on profiling of the DNA methylome of PCOS in different tissues provided consistent molecular evidence in support of epidemiological findings on disease comorbidity suggesting a possible autoimmune basis in the pathogenesis of the disease. We show that the field of epigenetics and epigenomics could serve to link molecular regulatory mechanisms with disease development and disease manifestation which could contribute to PCOS prevention and treatment and eventually promote reproductive health in fertile age women. We summarize the up-to-date findings and discuss the implications of various studies and point to new avenues of research on PCOS in the rapidly developing field of epigenetics and epigenomics.

Toosendanin Induces Lung Squamous Cell Carcinoma Cell Apoptosis and Inhibits Tumor Progression via the BNIP3/AMPK Signaling Pathway.

Lung squamous cell carcinoma (LUSC) is the second most common type of non-small cell lung cancer. Toosendanin can target critical cancer cell survival and proliferation. However, the function of toosendanin in LUSC is limited. Cancer cell proliferative capacity is detected using cell morphology, colony formation, and flow cytometry. The invasiveness of the cells is detected by a Transwell assay, western blotting, and RT-qPCR. Nude mice are injected with H226 (1×106) and received an intraperitoneal injection of toosendanin every 2 days for 21 days. RNA sequence transcriptome analysis is performed on toosendanin-treated cells to identify target genes and signaling pathways. With increasing concentrations of toosendanin, the rate of cell proliferation decreases and apoptotic cells increases. The number of migrated cells significantly reduces and epithelial-mesenchymal transition is reversed. Injection of toosendanin in nude mice leads to a reduction in tumor volume, weight, and the number of metastatic tumors. Furthermore, KEGG shows that genes related to the AMPK pathway are highly enriched. BNIP3 is the most differentially expressed gene, and its expression along with phosphorylated-AMPK significantly increases in toosendanin-treated cells. Toosendanin exerts anticancer effects, induces apoptosis in LUSC cells, and inhibits tumor progression via the BNIP3/AMPK signaling pathway.

Quality changes in Chinese high-quality indica rice under different storage temperatures with varying initial moisture contents.

The planting area of high-quality indica rice varieties has been growing rapidly in China. However, the storage characteristics of these varieties remains unclear. In this research, different moisture contents (13.5, 14.5, and 15.5%) of high-quality rice (variety Xiadao No.1) were stored at different temperatures (15, 20, 25, and 30°C) for 360 d, and then evaluated for lipid metabolism, redox enzyme activities, fatty acid composition, and sensory attributes. With the prolongation of storage, rice displayed an upward trend in fatty acid value, malondialdehyde content, and cooked rice hardness and a downward trend in contents of total fat and non-starch lipid, peroxidase and catalase activities, and sensory score of cooked rice. The change trends of these quality parameters were aggravated by elevating storage temperature and moisture content. Linoleic acid content of rice generally decreased with prolonged storage. After 300 d of storage, rice with initial moisture content of 13.5% at 30°C showed a fatty acid value of higher than 30 mg KOH/100 g, while rice of other two initial moisture contents reached similar level at 25°C. After the whole storage period, only rice with initial moisture contents of 13.5 and 14.5% stored at 15°C had a sensory score of higher than 60. These results suggested that the aging process of high-quality rice can be inhibited by decreasing the storage temperature and initial moisture content. These results can provide reference for grain storage enterprises to select proper storage condition to store high-quality rice.

Usenamine A triggers NLRP3/caspase-1/GSDMD-mediated pyroptosis in lung adenocarcinoma by targeting the DDX3X/SQSTM1 axis.

BACKGROUND: Usenamine A (C18H17NO6) is a newly developed, natural anticancer drug that reportedly exerts low toxicity. The therapeutic efficacy and underlying mechanisms of usenamine A in lung adenocarcinoma (LUAD) remain poorly understood. We aimed to explore the therapeutic effects and molecular mechanisms through which usenamine A inhibits LUAD tumorigenesis. METHODS: We used LUAD cell lines H1299 and A549 in the present study. CCK-8 and colony formation assays were performed to analyze cell proliferation. Cell migration, invasion, and apoptosis were evaluated using wound-healing, transwell, and flow cytometric assays, respectively. Levels of reactive oxygen species were measured using a DCFH-DA probe. Inflammatory factors (lactate dehydrogenase, interleukin [IL]-1ß, and IL-18) were detected using enzyme-linked immunosorbent assays. Western blotting was performed to determine the expression of NOD-like receptor pyrin 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) pathway-related proteins. Pyroptosis was detected using transmission electron microscopy. The interaction and co-localization of DDX3X and sequestosome 1 (SQSTM1) were identified using co-immunoprecipitation and immunofluorescence assays, respectively. For in vivo assessment, we established a xenograft model to validate the usenamine A-mediated effects and mechanisms of action in LUAD. RESULTS: Usenamine A inhibited the proliferation, migration, and invasion of LUAD cells. Furthermore, usenamine A induced NLRP3/caspase-1/GSDMD-mediated pyroptosis in LUAD cells. Usenamine A upregulated DDX3X expression to trigger pyroptosis. DDX3X interacted with SQSTM1, which is responsible for inducing pyroptosis. In vivo, usenamine A suppressed LUAD tumorigenesis by triggering NLRP3/caspase-1/GSDMD-mediated pyroptosis via the upregulation of the DDX3X/SQSTM1 axis. CONCLUSIONS: Usenamine A was found to induce NLRP3/caspase-1/GSDMD-mediated pyroptosis in LUAD by upregulating the DDX3X/SQSTM1 axis.

Genetic investigation into ethnic disparity in polycystic ovarian syndrome.

Polycystic ovarian syndrome is universally the most common endocrinopathy in women of reproductive age. It is characterized by composite clinical phenotypes reflecting the reproductive impact of ovarian dysfunction (androgen excess, oligo-/anovulation, polycystic ovary) and metabolic abnormalities (insulin resistance, obesity) with widely varying symptoms among the affected. Studies have shown a clear pattern of disparity in clinical manifestations of its component phenotypes across ethnic populations. Recent genetic association studies suggested differential genetic background that could contribute to the observed ethnic disparity. We summarize the current status in genetic studies of the disorder in different populations with a focus on ethnicity. Especially, we highlight and discuss the applications of recent developments in DNA sequencing, global transcriptional and epigenetic profiling that could help to unravel the molecular basis of the interethnic difference in the pathogenesis of the syndrome. It is hoped that identification and characterization of population-specific structural genetic and functional genomic patterns could help to not only deepen our understanding of the aetiology but also develop more efficient strategies for treatment and prevention of polycystic ovarian syndrome.

TMPOP2 Inhibition Suppresses Pancreatic Cancer Cell Migration and Development by Repressing The JNK/STAT3 Pathway.

Pancreatic cancer is a malignancy with a poor prognosis and high mortality. The lincRNA TMPOP2 is highly expressed in gynecological cancers and may exhibit tumor-promoting functions. However, the function of TMPOP2 in pancreatic cancer is limited. TMPOP2 expression in pancreatic cancer and adjacent tissues is analyzed from The Cancer Genome Atlas (TCGA) and GTEx database. It shows the high expression of TMPOP2 in pancreatic cancer tissues. Similar results are observed in resected pancreatic adenocarcinoma tumors and adjacent tissues from 20 patients and the relative cell lines. When the pancreatic cell lines are transfected with si-TMPOP2, it shows that TMPOP2 downregulation inhibits the cells migration and EMT. Furthermore, the potential mechanism is explored by detecting the expression of c-Jun N-terminal kinase (JNK), phosphorylated JNK, signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3. It suggests that TMPOP2 knockdown inactivates JNK and STAT3 phosphorylation. When a JNK activator (anisomycin) is added to the cells with si-NC or si-TMPOP2, it can partially reverse the migration and EMT inhibition of the cells with inhibited TMPOP2. TMPOP2 inhibition suppresses the migration and EMT of pancreatic cancer by repressing the JNK/STAT3 pathway. Thus, this may be a novel target for pancreatic cancer therapy.

Pulmonary artery aneurysm protruding into the bronchus as an endobronchial mass: A case report.

BACKGROUND: Pulmonary artery (PA) aneurysms are usually diagnosed radiographically and present as small or large lesions resembling inflammation or a neoplasm on chest radiography. It has rarely been reported as an endobronchial mass. CASE SUMMARY: We report the case of a 64-year-old man who presented with recurrent hemoptysis. Bronchoscopy revealed a tumorous protrusion blocking the right middle lobe bronchus, which was confirmed to be a PA aneurysm using endobronchial ultrasound bronchoscopy and computed tomography angiography. CONCLUSION: Although endobronchial PA aneurysms are rare, bronchoscopists need to add this lesion to the list of endobronchial masses for which a biopsy is to be assiduously avoided.

Nucleophosmin promotes lung adenocarcinoma cell proliferation, migration and invasion by activating the EGFR/MAPK signaling pathway.

Lung adenocarcinoma (LUAD) is the main cause of death globally. The present study investigated the prognostic value and functional verification of nucleophosmin (NPM1) in LUAD. LUAD and normal samples from The Cancer Genome Atlas were analyzed to identify whether NPM1 is associated with LUAD prognosis. NPM1 protein expression level was verified by western blotting. Cell proliferation, migration and invasion were detected by Cell Counting Kit­8, wound healing and Transwell assays, respectively. EGFR/MAPK pathway­related proteins [phosphorylated (p)­EGFR/EGFR, p­MEK/MEK, and p­ERK/ERK] expression was measured through western blotting. A xenograft tumor mice model was constructed to perform the in vivo verification. NPM1 was upregulated in LUAD cells, and high­level NPM1 indicated poor prognosis in patients with LUAD. In vitro experiments revealed that NPM1 knockdown inhibited LUAD cell proliferation, migration and invasion. Moreover, protein expression of p­EGFR/EGFR, p­MEK/MEK and p­ERK/ERK was reduced with the NPM1 silencing. Furthermore, EGF, an activator of the EGFR/MAPK pathway, reversed the effects of NPM1. In vivo experiments showed that NPM1 knockdown inhibited tumor growth and protein levels of p­EGFR/EGFR, p­MEK/MEK and p­ERK/ERK. NPM1 is related to the poor prognosis of LUAD and promotes the malignant progression of LUAD by activating the EGFR/MAPK pathway. This discovery provides a new potential therapeutic target for the diagnosis and treatment of LUAD.

Glycoprotein M6A Suppresses Lung Adenocarcinoma Progression via Inhibition of the PI3K/AKT Pathway.

Lung adenocarcinoma is the most common subtype of lung cancer and has high morbidity and mortality. Glycoprotein M6A (GPM6A) is a neuronal membrane glycoprotein reported to be related with cancer. However, studies on GPM6A in lung adenocarcinoma are rare. This study aimed to investigate the role of GPM6A in lung adenocarcinoma and its potential mechanism. GPM6A mRNA expression was analysed in 33 types of cancers using The Cancer Genome Atlas (TCGA) datasets. It was compared among normal lung tissues, lung adenocarcinoma tissues, and adjacent tissues using the Oncomine database. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to detect GPM6A expression in human lung adenocarcinoma cell lines (A549 and H1299) and normal pulmonary epithelial cells (BEAS-2B). When GPM6A was inhibited, cell proliferative capacity was detected by Cell Counting Kit 8 (CCK8), EdU, and colony formation assays. Cell migration ability was detected by wound healing and transwell assays. The expression of epithelial-mesenchymal transition (EMT) markers was detected by Western blotting (WB) and RT-qPCR. When GPM6A was overexpressed, cell proliferation and migration were detected again. Ten nude mice were subcutaneously injected with cells overexpressing GPM6A or empty vector, and the tumor size was recorded on day 14 and then measured every 3 days thereafter. The final tumor weight was measured on day 36. Furthermore, the expressions of phosphoinositide 3-kinase (PI3K), phosphorylated PI3K, AKT, and phosphorylated AKT were detected by WB. Results showed that GPM6A mRNA expression decreased in 15 types of tumors in TCGA dataset. GPM6A expression was lower in lung adenocarcinoma than in normal lung tissues or adjacent tissues in the Oncomine dataset. Similar results were found in lung adenocarcinoma cells. The function study showed that GPM6A downregulation enhanced the proliferation, migration, and EMT of lung adenocarcinoma cells, while GPM6A upregulation inhibited their development. The xenograft results suggested that GPM6A upregulation delayed tumor growth and reduced tumor weight. Moreover, WB showed that GPM6A knockdown activated the PI3K/AKT pathway, while GPM6A upregulation inhibited the activation of the PI3K/AKT pathway. In conclusion, GPM6A suppresses lung adenocarcinoma progression via inhibition of the PI3K/AKT pathway. Thus, GPM6A could be a possible treatment target for lung cancer therapy.

Intravascular large B-cell lymphoma with diffuse ground glass lesion on chest computed tomography diagnosed using transbronchial lung cryobiopsy: a case report.

A 68-year-old man was presented with high fever of unknown origin for 3 weeks and non-productive cough for 1 week. A chest computed tomography (CT) scan revealed multiple nodules and ground glass opacities (GGO) in both lungs. The patient was initially diagnosed with hypersensitivity pneumonitis based on the result of bronchoalveolar lavage fluids (BALF). After treatment with methylprednisolone for 2 weeks, the patient's fever recurred, with no resolution of lesions on chest CT. The patient consented to positron emission tomography (PET)/CT. It showed that fluorodeoxyglucose (FDG) metabolism was significantly increased in the spleen, whole skeleton, and both lungs, suggesting a malignant hematological disease. Large B-cell lymphoma was diagnosed by bone marrow puncture and flow cytometry. Transbronchial lung cryobiopsy was performed to evaluate the diffuse lung lesion. Hematoxylin-eosin (HE) staining showed diffuse infiltration of heterotypic cells in the pulmonary interstitial capillaries. Furthermore, immunohistochemical examination results suggested lung infiltration of B lymphohematopoietic system tumors. The patient was finally diagnosed as intravascular large B-cell lymphoma (IVLBCL). IVLBCL with diffuse lung ground glass lesions is very rare and difficult to diagnose. Transbronchial lung cryobiopsy, as an emerging procedure, plays an important role in the diagnosis of interstitial lung disease and has gained popularity for a lower complication rate and acquisition of more tissue samples.