High CENPM Gene Expression Predict Poor Survival Outcome in Lung Adenocarcinoma

Abstract Introduction: Lung adenocarcinoma is a disease with high morbidity and mortality. The aim of our study was to investigate the relationship between the gene expression of centromere protein M (CENPM) and its prognostic impact in lung adenocarcinoma.Method: By analyzing the data of lung adenocarcinoma in database, the CENPM gene expression in lung adenocarcinoma and its relationship with clinical stage and survival time were analyzed using datasets from The Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO) datasets. Genes associated with CENPM expression were analyzed and subjected to functional and pathway enrichment analysis. Finally, the genetic results and treatment and survival outcomes of 20 patients with lung adenocarcinoma from our hospital were analyzed.Result: CENPM transcripts were found to be highly expressed in lung adenocarcinoma as compared with normal tissues (3.628 VS. 2.227, P < 0.001). CENPM expression was positively associated with tumor stage (3.803 vs. 3.444, p < 0.001) and nodal stage (3.992 vs. 3.573, p < 0.001). Patients with low CENPM expression achieved better progression-free survival (45.9 months vs. 25.7months, p < 0.001) and overall survival (57.5 months vs. 47.5 months, p=0.001). The CENPM expression was negatively correlated with the infiltration of most immune cells in lung adenocarcinoma tissues and positively correlated with PD1 (r = 0.231, p < 0.001) and PD-L1 (r = 0.116, p < 0.007). CENPM-related genes were enriched in the set of genes with poor prognosis as well as the set of cell cycle-related genes in lung adenocarcinoma. CENPM expression was also negatively correlated with T lymphocyte and B lymphocyte signaling pathways. Finally, CENPM-related genes were related in Rho GTPases and ATR signaling pathways.Conclusion: Our findings demonstrate that CENPM gene is highly expressed and is associated with poor prognosis in lung adenocarcinoma.

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Upregulation of GNPNAT1 Predicts Poor Prognosis and Correlates With Immune Infiltration in Lung Adenocarcinoma

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.605754 ◽

2021 ◽

Vol 8 ◽

Author(s):

Wenting Liu ◽

Kaiting Jiang ◽

Jingya Wang ◽

Ting Mei ◽

Min Zhao ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Signaling Pathways ◽

Poor Prognosis ◽

Cox Regression ◽

Clinical Stage ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Clinical Value ◽

Cox Regression Analysis ◽

Normal Tissues

BackgroundGlucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a key enzyme in the hexosamine biosynthetic pathway (HBP), which functions as promoting proliferation in some tumors, yet its potential biological function and mechanism in lung adenocarcinoma (LUAD) have not been explored.MethodsThe mRNA differential expression of GNPNAT1 in LUAD and normal tissues was analyzed using the Cancer Genome Atlas (TCGA) database and validated by real-time PCR. The clinical value of GNPNAT1 in LUAD was investigated based on the data from the TCGA database. Then, immunohistochemistry (IHC) of GNPNAT1 was applied to verify the expression and clinical significance in LUAD from the protein level. The relationship between GNPNAT1 and epigenetics was explored using the cBioPortal database, and the miRNAs regulating GNPNAT1 were found using the miRNA database. The association between GNPNAT1 expression and tumor-infiltrating immune cells in LUAD was observed through the Tumor IMmune Estimation Resource (TIMER). Finally, Gene set enrichment analysis (GSEA) was used to explore the biological signaling pathways involved in GNPNAT1 in LUAD.ResultsGNPNAT1 was upregulated in LUAD compared with normal tissues, which was verified through qRT-PCR in different cell lines (P < 0.05), and associated with patients’ clinical stage, tumor size, and lymphatic metastasis status (all P < 0.01). Kaplan–Meier (KM) analysis suggested that patients with upregulated GNPNAT1 had a relatively poor prognosis (P < 0.0001). Furthermore, multivariate Cox regression analysis indicated that GNPNAT1 was an independent prognostic factor for LUAD (OS, TCGA dataset: HR = 1.028, 95% CI: 1.013–1.044, P < 0.001; OS, validation set: HR = 1.313, 95% CI: 1.130–1.526, P < 0.001). GNPNAT1 overexpression was correlated with DNA copy amplification (P < 0.0001), low DNA methylation (R = −0.52, P < 0.0001), and downregulation of hsa-miR-30d-3p (R = −0.17, P < 0.001). GNPNAT1 expression was linked to B cells (R = −0.304, P < 0.0001), CD4+T cells (R = −0.218, P < 0.0001), and dendritic cells (R = −0.137, P = 0.002). Eventually, GSEA showed that the signaling pathways of the cell cycle, ubiquitin-mediated proteolysis, mismatch repair and p53 were enriched in the GNPNAT1 overexpression group.ConclusionGNPNAT1 may be a potential prognostic biomarker and novel target for intervention in LUAD.

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Characteristics of the Immune Cell Infiltration Landscape in Gastric Cancer to Assistant Immunotherapy

Frontiers in Genetics ◽

10.3389/fgene.2021.793628 ◽

2022 ◽

Vol 12 ◽

Author(s):

Chenlu Li ◽

Jingjing Pan ◽

Yinyan Jiang ◽

Yan Yu ◽

Zhenlin Jin ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Signaling Pathways ◽

Poor Prognosis ◽

Immune Cell ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Therapeutic Responses

Background: Gastric cancer (GC) was usually associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity. It is urgent to screen reliable indices especially immunotherapy-associated parameters that can predict the therapeutic responses to immunotherapy of GC patients.Methods: Gene expression profile of 854 GC patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE84433) with their corresponding clinical and somatic mutation data. Based on immune cell infiltration (ICI) levels, molecular clustering classification was performed to identify subtypes and ICI scores in GC patients. After functional enrichment analysis of subtypes, we further explored the correlation between ICI scores and Tumor Mutation Burden (TMB) and the significance in clinical immunotherapy response.Results: Three subtypes were identified based on ICI scores with distinct immunological and prognostic characteristics. The ICI-cluster C, associated with better outcomes, was characterized by significantly higher stromal and immune scores, T lymphocytes infiltration and up-regulation of PD-L1. ICI scores were identified through using principal component analysis (PCA) and the low ICI scores were consistent with the increased TMB and the immune-activating signaling pathways. Contrarily, the high-ICI score cluster was involved in the immunosuppressive pathways, such as TGF-beta, MAPK and WNT signaling pathways, which might be responsible for poor prognosis of GC. External immunotherapy and chemotherapy cohorts validated the patients with lower ICI scores exhibited significant therapeutic responses and clinical benefits.Conclusion: This study elucidated that ICI score could sever as an effective prognostic and predictive indicator for immunotherapy in GC. These findings indicated that the systematic assessment of tumor ICI landscapes and identification of ICI scores have crucial clinical implications and facilitate tailoring optimal immunotherapeutic strategies.

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DDRE-40. BIOINFORMATICS ANALYSIS OF GRADE I AND III MENINGIOMA GENE EXPRESSION SUGGESTS MMP28 AS A POSSIBLE POSITIVE PROGNOSTIC INDICATOR

Neuro-Oncology ◽

10.1093/neuonc/noab196.324 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi83-vi83

Author(s):

Sharon Michelhaugh ◽

Gregory Dyson ◽

Rouba Ali-Fehmi ◽

Aliccia Bollig-Fischer ◽

Sandeep Mittal ◽

...

Keyword(s):

Gene Expression ◽

Signaling Pathways ◽

Surgical Resection ◽

Poor Prognosis ◽

Molecular Mechanisms ◽

Prognostic Indicator ◽

Pathway Enrichment Analysis ◽

Expression Ratio ◽

Mesenchymal Transition ◽

Grade Iii

Abstract Meningiomas are the most common primary brain tumor. Grade I meningiomas are slow growing with a good prognosis following surgical resection. High grade meningiomas (II and III) are more aggressive with greater rates of recurrence and poor prognosis despite surgical resection and radiotherapy. This study sought to identify key pathways and genes that contribute to the molecular mechanisms that separate these distinct meningioma phenotypes. FFPE specimens were evaluated and graded by a pathologist. Total RNA was extracted from tissue curls and RNA samples were measured with the Illumina DASL whole genome gene expression assay (n = 29,374 probes). A log2 transformation was applied to all of the data and quantile normalization using 21 samples. A t-test of the log2 expression of the 10 grade III samples and 11 grade I samples resulted in 1505 differentially expressed genes. The GeneCard Suite’s GeneAnalytics tool was used to perform pathway enrichment analysis. Similar to other comparable data sets, DNA Damage, Cell Cycle, EGF/EGFR Signaling, TGF-Beta Signaling, and PI3K-AKT Signaling pathways were among the 20 enriched pathways. Notably, matrix metalloprotease 28 (MMP28, also known as epilysin) was down regulated in grade III meningiomas compared to grade I (III/I expression ratio 0.315; P=0.015). MMP28 is expressed in numerous tissues including the nervous system during development and regeneration. In cancer, MMP28 is thought to enhance epithelial to mesenchymal transition by altering the TGF-B signaling pathways. MMP28 is an indicator of poor prognosis for pancreatic, lung, gastric and hepatic cancers as well as glioblastoma. However, MMP28 has also been reported as down regulated during malignant transformation in colon cancer. Our data suggest that MMP28 may have an alternative role in meningioma and serve as a positive prognostic indicator.

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The overexpression of FKBP4 in patients with lung adenocarcinoma predicts poor prognosis and tumor progression

10.21203/rs.3.rs-733351/v1 ◽

2021 ◽

Author(s):

Sha Tian ◽

Shang qing Wang ◽

Piao Zheng ◽

Xu Zhu ◽

Huan Han ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Signaling Pathways ◽

Cancer Progression ◽

Poor Prognosis ◽

Cox Regression ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Clinicopathological Parameters ◽

Poor Overall Survival ◽

Kaplan Meier

Abstract Background: The FK506-binding protein 4 ( FKBP4 ), a tumor-related gene, plays a vital role in tumorigenesis and cancer progression. The study is aimed to clarify the effect of FKBP4 in lung adenocarcinoma (LUAD). Methods: Relying on The Cancer Genome Atlas (TCGA) cohort, the FKBP4 expression difference between LUAD tissues and non-tumor tissues was first detected, and verified with public tissue microarrays (TMAs), clinical LUAD specimen cohort and Gene Expression Omnibus (GEO) cohort. Then, logistic regression analysis and chi-square test were applied to detect the correlation between FKBP4 expression and clinicopathological parameters. Kaplan-Meier survival analysis and Cox regression model were utilized to evaluate the effect of FKBP4 expression on survival. Signaling pathways related to LUAD were obtained via employing Gene Set Enrichment Analysis (GSEA). Results: The FKBP4 expression level in LUAD samples was dramatically higher than that in non-tumor samples. High FKBP4 expression in LUAD is associated with gender, pathological stage, T classification, lymph node metastasis and distant metastasis. The Kaplan-Meier curve indicated a poor prognosis for LUAD patients with high FKBP4 expression. Multivariate analysis suggested that the high FKBP4 expression was a vital independent predictor of poor overall survival (OS). GSEA showed that a total of 15 signaling pathways were enriched in samples with high FKBP4 expression phenotype. Conclusions: FKBP4 may be an oncogene in LUAD, and is promised to become a prognostic indicator and therapeutic target for LUAD.

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Identification of VWF as a Novel Biomarker in Lung Adenocarcinoma by Comprehensive Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.639600 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yi He ◽

Ruijie Liu ◽

Mei Yang ◽

Wu Bi ◽

Liuyin Zhou ◽

...

Keyword(s):

Gene Expression ◽

Extracellular Matrix ◽

Lung Adenocarcinoma ◽

Malignant Tumors ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

High Morbidity ◽

Hub Genes ◽

Normal Tissues ◽

New Biomarkers

Lung adenocarcinoma (LUAD) is one of the most malignant tumors with high morbidity and mortality worldwide due to the lack of reliable methods for early diagnosis and effective treatment. It’s imperative to study the mechanism of its development and explore new biomarkers for early detection of LUAD. In this study, the Gene Expression Omnibus (GEO) dataset GSE43458 and The Cancer Genome Atlas (TCGA) were used to explore the differential co-expressed genes between LUAD and normal samples. Three hundred sixity-six co-expressed genes were identified by differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) method. Those genes were mainly enriched in ameboidal-type cell migration (biological process), collagen-containing extracellular matrix (cell component), and extracellular matrix structure constituent (molecular function). The protein-protein network (PPI) was constructed and 10 hub genes were identified, including IL6, VWF, CDH5, PECAM1, EDN1, BDNF, CAV1, SPP1, TEK, and SELE. The expression level of hub genes was validated in the GEPIA database, compared with normal tissues, VWF is lowly expressed and SPP1 is upregulated in LUAD tissues. The survival analysis showed increased expression of SPP1 indicated unfavorable prognosis whereas high expression of VWF suggested favorable prognosis in LUAD (p < 0.05). Based on the immune infiltration analysis, the relationship between SPP1 and VWF expression and macrophage, neutrophil, and dendritic cell infiltration was weak in LUAD. Quantitative real-time PCR (qRT-PCR) and western blotting were used to validate the expression of VWF and SPP1 in normal human bronchial epithelial (HBE) cell and three LUAD cell lines, H1299, H1975, and A549. Immunohistochemistry (IHC) was further performed to detect the expression of VWF in 10 cases LUAD samples and matched normal tissues. In summary, the data suggest that VWF is a potential novel biomarker for prognosis of LUAD.

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Construction of a Prognostic Model in Lung Adenocarcinoma Based on Ferroptosis-Related Genes

Frontiers in Genetics ◽

10.3389/fgene.2021.739520 ◽

2021 ◽

Vol 12 ◽

Author(s):

Min Liang ◽

Mafeng Chen ◽

Yinghua Zhong ◽

Shivank Singh ◽

Shantanu Singh

Keyword(s):

Gene Expression ◽

Lung Adenocarcinoma ◽

Risk Score ◽

Prognostic Model ◽

Cox Regression ◽

Malignant Tumors ◽

Clinical Stage ◽

Prognostic Significance ◽

Low Risk ◽

The Cancer Genome Atlas

Background: Lung adenocarcinoma is one of the most common malignant tumors of the respiratory system, ranking first in morbidity and mortality among all cancers. This study aims to establish a ferroptosis-related gene-based prognostic model to investigate the potential prognosis of lung adenocarcinoma.Methods: We obtained gene expression data with matching clinical data of lung adenocarcinoma from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The ferroptosis-related genes (FRGs) were downloaded from three subgroups in the ferroptosis database. Using gene expression differential analysis, univariate Cox regression, and LASSO regression analysis, seven FRGs with prognostic significance were identified. The result of multivariate Cox analysis was utilized to calculate regression coefficients and establish a risk-score formula that divided patients with lung adenocarcinoma into high-risk and low-risk groups. The TCGA results were validated using GEO data sets. Then we observed that patients divided in the low-risk group lived longer than the overall survival (OS) of the other. Then we developed a novel nomogram including age, gender, clinical stage, TNM stage, and risk score.Results: The areas under the curves (AUCs) for 3- and 5-years OS predicted by the model were 0.823 and 0.852, respectively. Calibration plots and decision curve analysis also confirmed the excellent predictive performance of the model. Subsequently, gene function enrichment analysis revealed that the identified FRGs are important in DNA replication, cell cycle regulation, cell adhesion, chromosomal mutation, oxidative phosphorylation, P53 signaling pathway, and proteasome processes.Conclusions: Our results verified the prognostic significance of FRGs in patients with lung adenocarcinoma, which may regulate tumor progression in a variety of pathways.

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Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas

Cancers ◽

10.3390/cancers13010158 ◽

2021 ◽

Vol 13 (1) ◽

pp. 158

Author(s):

Valentina Condelli ◽

Giovanni Calice ◽

Alessandra Cassano ◽

Michele Basso ◽

Maria Grazia Rodriquenz ◽

...

Keyword(s):

Gene Expression ◽

Poor Prognosis ◽

Cpg Island ◽

Colon Adenocarcinoma ◽

Gene Signature ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Cpg Island Methylator Phenotype ◽

Prognostic Information ◽

Global Methylation

Epigenetics is involved in tumor progression and drug resistance in human colorectal carcinoma (CRC). This study addressed the hypothesis that the DNA methylation profiling may predict the clinical behavior of metastatic CRCs (mCRCs). The global methylation profile of two human mCRC subgroups with significantly different outcome was analyzed and compared with gene expression and methylation data from The Cancer Genome Atlas COlon ADenocarcinoma (TCGA COAD) and the NCBI GENE expression Omnibus repository (GEO) GSE48684 mCRCs datasets to identify a prognostic signature of functionally methylated genes. A novel epigenetic signature of eight hypermethylated genes was characterized that was able to identify mCRCs with poor prognosis, which had a CpG-island methylator phenotype (CIMP)-high and microsatellite instability (MSI)-like phenotype. Interestingly, methylation events were enriched in genes located on the q-arm of chromosomes 13 and 20, two chromosomal regions with gain/loss alterations associated with adenoma-to-carcinoma progression. Finally, the expression of the eight-genes signature and MSI-enriching genes was confirmed in oxaliplatin- and irinotecan-resistant CRC cell lines. These data reveal that the hypermethylation of specific genes may provide prognostic information that is able to identify a subgroup of mCRCs with poor prognosis.

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Functions and clinical significance of KLRG1 in the development of lung adenocarcinoma and immunotherapy

BMC Cancer ◽

10.1186/s12885-021-08510-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiaodong Yang ◽

Yuexin Zheng ◽

Zhihai Han ◽

Xiliang Zhang

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Lung Adenocarcinoma ◽

Molecular Mechanisms ◽

Killer Cell ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Normal Lung ◽

Using Data ◽

Low Expression

Abstract Background As a marker of differentiation, Killer cell lectin like receptor G1 (KLRG1) plays an inhibitory role in human NK cells and T cells. However, its clinical role remains inexplicit. This work intended to investigate the predictive ability of KLRG1 on the efficacy of immune-checkpoint inhibitor in the treatment of lung adenocarcinoma (LUAD), as well as contribute to the possible molecular mechanisms of KLRG1 on LUAD development. Methods Using data from the Gene Expression Omnibus, the Cancer Genome Atlas and the Genotype-Tissue Expression, we compared the expression of KLRG1 and its related genes Bruton tyrosine kinase (BTK), C-C motif chemokine receptor 2 (CCR2), Scm polycomb group protein like 4 (SCML4) in LUAD and normal lung tissues. We also established stable LUAD cell lines with KLRG1 gene knockdown and investigated the effect of KLRG1 knockdown on tumor cell proliferation. We further studied the prognostic value of the four factors in terms of overall survival (OS) in LUAD. Using data from the Gene Expression Omnibus, we further investigated the expression of KLRG1 in the patients with different responses after immunotherapy. Results The expression of KLRG1, BTK, CCR2 and SCML4 was significantly downregulated in LUAD tissues compared to normal controls. Knockdown of KLRG1 promoted the proliferation of A549 and H1299 tumor cells. And low expression of these four factors was associated with unfavorable overall survival in patients with LUAD. Furthermore, low expression of KLRG1 also correlated with poor responses to immunotherapy in LUAD patients. Conclusion Based on these findings, we inferred that KLRG1 had significant correlation with immunotherapy response. Meanwhile, KLRG1, BTK, CCR2 and SCML4 might serve as valuable prognostic biomarkers in LUAD.

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AB0005 IDENTIFICATION OF KEY GENES AND PATHWAYS FOR PSORIASIS BASED ON GEO DATABASES BY BIOINFORMATICS ANALYSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1773 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1037.2-1038

Author(s):

X. Sun ◽

S. X. Zhang ◽

S. Song ◽

T. Kong ◽

C. Zheng ◽

...

Keyword(s):

Gene Expression ◽

Signaling Pathways ◽

Differentially Expressed Genes ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Shanxi Province ◽

Receptor Interaction ◽

Term Therapy ◽

Pathway Enrichment Analysis ◽

Key Genes

Background:Psoriasis is an immune-mediated, genetic disease manifesting in the skin or joints or both, and also has a strong genetic predisposition and autoimmune pathogenic traits1. The hallmark of psoriasis is sustained inflammation that leads to uncontrolled keratinocyte proliferation and dysfunctional differentiation. And it’s also a chronic relapsing disease, which often necessitates a long-term therapy2.Objectives:To investigate the molecular mechanisms of psoriasis and find the potential gene targets for diagnosis and treating psoriasis.Methods:Total 334 gene expression data of patients with psoriasis research (GSE13355 GSE14905 and GSE30999) were obtained from the Gene Expression Omnibus database. After data preprocessing and screening of differentially expressed genes (DEGs) by R software. Online toll Metascape3 was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs. Interactions of proteins encoded by DEGs were discovered by Protein-protein interaction network (PPI) using STRING online software. Cytoscape software was utilized to visualize PPI and the degree of each DEGs was obtained by analyzing the topological structure of the PPI network.Results:A total of 611 DEGs were found to be differentially expressed in psoriasis. GO analysis revealed that up-regulated DEGs were mostly associated with defense and response to external stimulus while down-regulated DEGs were mostly associated with metabolism and synthesis of lipids. KEGG enrichment analysis suggested they were mainly enriched in IL-17 signaling, Toll-like receptor signaling and PPAR signaling pathways, Cytokine-cytokine receptor interaction and lipid metabolism. In addition, top 9 key genes (CXCL10, OASL, IFIT1, IFIT3, RSAD2, MX1, OAS1, IFI44 and OAS2) were identified through Cytoscape.Conclusion:DEGs of psoriasis may play an essential role in disease development and may be potential pathogeneses of psoriasis.References:[1]Boehncke WH, Schon MP. Psoriasis. Lancet 2015;386(9997):983-94. doi: 10.1016/S0140-6736(14)61909-7 [published Online First: 2015/05/31].[2]Zhang YJ, Sun YZ, Gao XH, et al. Integrated bioinformatic analysis of differentially expressed genes and signaling pathways in plaque psoriasis. Mol Med Rep 2019;20(1):225-35. doi: 10.3892/mmr.2019.10241 [published Online First: 2019/05/23].[3]Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019;10(1):1523. doi: 10.1038/s41467-019-09234-6 [published Online First: 2019/04/05].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

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MicroRNA-3666 inhibits lung cancer cell proliferation, migration, and invasiveness by targeting BPTF

Biochemistry and Cell Biology ◽

10.1139/bcb-2018-0301 ◽

2019 ◽

Vol 97 (4) ◽

pp. 415-422 ◽

Cited By ~ 3

Author(s):

Linqing Pan ◽

Zhipeng Tang ◽

Lina Pan ◽

Ranran Tang

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Lung Adenocarcinoma ◽

Signaling Pathways ◽

Histological Grade ◽

Clinical Stage ◽

Luciferase Reporter ◽

Advanced Clinical Stage ◽

Mesenchymal Transition ◽

Adenocarcinoma Cell

A previous study by our group indicted that overexpression of bromodomain PHD-finger transcription factor (BPTF) occurs in lung adenocarcinoma, and is closely associated with advanced clinical stage, higher numbers of metastatic lymph nodes, the occurrence of distant metastasis, low histological grade, and poor prognosis. Down-regulation of BPTF inhibited lung adenocarcinoma cell proliferation and promoted lung adenocarcinoma cell apoptosis. The purpose of this study is to identify valuable microRNAs (miRNAs) that target BPTF to modulate lung adenocarcinoma cell proliferation. In our results, we found that miR-3666 was notably reduced in lung adenocarcinoma tissues and cell lines. Using an miR-3666 mimic, we discovered that cell proliferation, migration, and invasiveness were suppressed by miR-3666 overexpression, but these were all enhanced when the expression of miR-3666 was reduced. Moreover, bioinformatics analysis using the TargetScan database and miRanda software suggested a putative target site in BPTF 3′-UTR. Furthermore, using a luciferase reporter assay, we verified that miR-3666 directly targets the 3′-UTR of BPTF. Using Western blot we discovered that overexpression of miR-3666 negatively regulates the protein expression of BPTF. Finally, we identified that the PI3K–AKT and epilthelial–mesenchymal transition (EMT) signaling pathways were inhibited by miR-3666 overexpression in lung cancer cells. In conclusion, our data indicate that miR-3666 could play an essential role in cell proliferation, migration, and invasiveness by targeting BPTF and partly inhibiting the PI3K–AKT and EMT signaling pathways in human lung cancers.

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