scholarly journals miR-30a-5p Regulates Viability, Migration, and Invasion of Lung Adenocarcinoma Cells via Targeting ECT2

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Sangsang Chen ◽  
Xuqing Zhu ◽  
Jing Zheng ◽  
Tingting Xu ◽  
Yinmin Xu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Clinical Stage ◽  
Regulatory Gene ◽  
Mature Mirnas ◽  
The Cancer Genome Atlas ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Cancer Genome Atlas ◽  
Mirnas Expression ◽  
Cell Transforming

Objective. The abnormal expression of epithelial cell transforming sequence 2 (ECT2) is often considered the driving factor for the growth and invasion of tumors. This study was performed to investigate the regulatory effect of miR-30a-5p and ECT2 on lung adenocarcinoma (LUAD), which provides a basis for the effective clinical treatment of LUAD. Methods. The mature miRNAs, expression data of mRNAs, and clinical data of LUAD were downloaded from The Cancer Genome Atlas (TCGA). The expression levels of ECT2 mRNA and miR-30a-5p in cancer cell lines were detected by qRT-PCR. Western blot was performed to test the expression of ECT2 protein. The targeting relationship between miR-30a-5p and ECT2 was verified by dual-luciferase assay. The CCK-8 method and Transwell assay were conducted to test the viability, migratory, and invasive abilities of cells. Results. ECT2 expression was upregulated in LUAD and was significantly correlated with the LUAD clinical stage and pathologic T stage, and the expression of its upstream regulatory gene miR-30a-5p was downregulated. miR-30a-5p targeted ECT2 in LUAD. Downregulation of ECT2 could inhibit the viability, migration, and invasion of LUAD cells, which could be reversed by simultaneously suppressing the expression of miR-30a-5p. Conclusion. Our results suggested that miR-30a-5p repressed the malignant progression of LUAD via downregulating ECT2. miR-30a-5p and ECT2 may be effective targets for LUAD patients.

scholarly journals Lymphocyte cytosolic protein 2 is a novel prognostic marker in lung adenocarcinoma

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110596
Author(s):  
Yishan Huo ◽  
Kainan Zhang ◽  
Songtao Han ◽  
Yangchun Feng ◽  
Yongxing Bao
Keyword(s):  
Lung Adenocarcinoma ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Immune Functions ◽  
Cytosolic Protein ◽  
Programmed Death ◽  
Cancer Genome Atlas ◽  
Using Data

Objective Lymphocyte cytosolic protein 2 (LCP2) is often ectopically expressed in various human tumors. However, the clinical significance and role of LCP2 in lung adenocarcinoma (LUAD) remain unclear. This study explored the prognostic significance of LCP2 in LUAD patients. Methods LCP2 expression in LUAD tissues was analyzed using data from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Western blotting was employed to detect LCP2 expression in LUAD. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to explore signaling pathways mediated by LCP2 co-regulatory genes. Immunohistochemistry was used to examine levels of LCP2 and programmed death ligand 1 (PD-L1) in 68 LUAD patients. Associations between LCP2 expression and clinicopathological features, prognoses, and PD-L1 levels among the LUAD in-patients were analyzed. Results Among the 68 LUAD in-patients, LCP2 expression was correlated with clinical stage and lymph node metastasis. LUAD patients with high LCP2 expression were associated with increased overall survival. LCP2 expression may be associated with an enrichment of several immune functions. Moreover, our immunohistochemistry results demonstrated that LCP2 expression was positively correlated with PD-L1 expression in LUAD tissues. Conclusions In the study, LCP2 was found to be a favorable prognostic biomarker in LUAD patients.

scholarly journals Cyanidin-3-glucoside suppresses the progression of lung adenocarcinoma by downregulating TP53I3 and inhibiting PI3K/AKT/mTOR pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaojun Chen ◽  
Weixia Zhang ◽  
Xiuzhen Xu
Keyword(s):  
Lung Adenocarcinoma ◽  
Mammalian Target Of Rapamycin ◽  
A549 Cells ◽  
Mtor Pathway ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Phosphatidylinositol 3 Kinase ◽  
Cell Clones ◽  
Cancer Genome Atlas

Abstract Background The aim of this study is to unravel the role of Cyanidin-3-glucoside (C3G) and its potential mechanisms in lung adenocarcinoma (LUAD). Methods The cell clones, proliferation, apoptosis, migration, and invasion in H1299 and A549 cells were determined by colony formation assay, 5-ethynyl-20 deoxyuridine (EdU) assay, flow cytometry, and transwell assay, respectively. The expression of p53-induced gene 3 (TP53I3) was assessed and the prognostic values of TP53I3 in LUAD via the dataset from the Cancer Genome Atlas (TCGA). In addition, the mRNA and protein expressions were detected by quantitative real-time PCR (qRT-PCR) and western blot. Results C3G inhibited the proliferation, migration, and invasion of, and also promoted the apoptosis in H1299 and A549 cells. The database of TCGA showed TP53I3 was highly expressed in LUAD tissues and correlated with the poor prognosis of LUAD patients. Moreover, we also found that C3G inhibited the proliferation, migration and invasion, and promoted apoptosis in H1299 and A549 cells by downregulating TP53I3. Additionally, C3G could inhibit the activation of phosphatidylinositol 3′-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in H1299 and A549 cells by downregulating TP53I3. Conclusion This study demonstrated that C3G could inhibit the proliferation, migration and invasion, and also facilitate the apoptosis through downregulating TP53I3 and inhibiting PI3K/AKT/mTOR pathway in LUAD.

Identification of predictive biomarker for immunotherapy by associating with CD8+T cell Infiltration in lung adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21177-e21177
Author(s):  
Puyuan Xing ◽  
Teng Li ◽  
Han Wang ◽  
Lin Yang ◽  
Guoqiang Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Predictive Biomarkers ◽  
Tumor Infiltrating Lymphocytes ◽  
Predictive Performance ◽  
Predictive Biomarker ◽  
Pooled Analysis ◽  
The Cancer Genome Atlas ◽  
T Cell Infiltration ◽  
Or Groups ◽  
Cancer Genome Atlas

e21177 Background: Tumor immune microenvironment (TIME) has been proved associated with response to immunotherapy(I/O). We hypothesized that screening potential mutation pattern which could significantly impact the tumor infiltrating lymphocytes(TILs) can help us to identify predictive biomarkers for I/O in Lung adenocarcinoma(LUAD). Methods: Multiple-dimensional data from The Cancer Genome Atlas LUAD cohort (n = 514) was used for building a mathematical model beween mutation signature and CD8+TIL score (based on MCP-counter). An independent public validation cohort (cohort 1: LUAD, n = 598) were used to assess the immunotherapeutic predictive performance of the potential mutation patterns. Results: Top 100 gene associated with CD8+TIL score were selected based on MC+ model which can provides the minimum non-convexity of the penalized loss given the level of bias. Seven TIME genes (SPTA1 coef 0.09; MET coef 0.02; HSD3B1 coef -0.00; STAT4 coef -0.01; EGFR coef -0.08; PIK3CB coef -0.08; KEAP1 coef -0.24) were generated by taking the intersection of the top 100 mutant genes and FoundationOne (F1) CDx NGS 315 genes panel and verified in cohort 1. Survival analysis showed that SPTA1mt was the only one that associated with both significantly longer PFS (median PFS 3.15 vs 2.89 months; HR 0.65; 95% CI 0.45 to 0.93; p = 0.02) and OS (median PFS 15.08 vs 7.36 months; HR 0.59; 95% CI 0.40 to 0.88; p = 0.01) for patients who received I/O compared with chemotherapy(CT) among seven TIME genes. In order to test our hypothesis fully, a pooled analysis of SPTA1mt (a core positive predictors of CD8+TILs) and KEAP1mt (a core negative predictors for CD8+TILs ) were conducted and yielded that co occurrence of SPTA1mt and KEAP1mt had a compound effects for TIME. The validation showed that co mutation with SPTA1mt was accompanied by an decrease HR for I/O vs. CT in both PFS (HR S+K vs. K only 0.59 vs 1.56) and OS (HR S+K vs. K only 0.39 vs 0.80) for KEAP1mt patients. Conclusions: Our data show that it is feasible to identify individuals or groups of individual with specific mutations to immunotherapy responses from TIME view. SPTA1mt was a core predictors for higher CD8+ TILs and can be identified as a predictive biomarker for benefit from I/O compared with CT. Prospective studies are warranted for further investigation.

scholarly journals Visual Display of 5p-arm and 3p-arm miRNA Expression with a Mobile Application

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Chao-Yu Pan ◽  
Wei-Ting Kuo ◽  
Chien-Yuan Chiu ◽  
Wen-chang Lin
Keyword(s):  
Mirna Expression ◽  
Expression Patterns ◽  
Mirna Gene ◽  
Visual Display ◽  
Mature Mirnas ◽  
Mobile App ◽  
The Cancer Genome Atlas ◽  
Rna Seq ◽  
Cancer Genome Atlas ◽  
User Friendly

MicroRNAs (miRNAs) play important roles in human cancers. In previous studies, we have demonstrated that both 5p-arm and 3p-arm of mature miRNAs could be expressed from the same precursor and we further interrogated the 5p-arm and 3p-arm miRNA expression with a comprehensive arm feature annotation list. To assist biologists to visualize the differential 5p-arm and 3p-arm miRNA expression patterns, we utilized a user-friendly mobile App to display. The Cancer Genome Atlas (TCGA) miRNA-Seq expression information. We have collected over 4,500 miRNA-Seq datasets from 15 TCGA cancer types and further processed them with the 5p-arm and 3p-arm annotation analysis pipeline. In order to be displayed with the RNA-Seq Viewer App, annotated 5p-arm and 3p-arm miRNA expression information and miRNA gene loci information were converted into SQLite tables. In this distinct application, for any given miRNA gene, 5p-arm miRNA is illustrated on the top of chromosome ideogram and 3p-arm miRNA is illustrated on the bottom of chromosome ideogram. Users can then easily interrogate the differentially 5p-arm/3p-arm expressed miRNAs with their mobile devices. This study demonstrates the feasibility and utility of RNA-Seq Viewer App in addition to mRNA-Seq data visualization.

scholarly journals Deciphering N6-Methyladenosine-Related Genes Signature to Predict Survival in Lung Adenocarcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Jie Zhu ◽  
Min Wang ◽  
Daixing Hu
Keyword(s):  
Lung Adenocarcinoma ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Consensus Clustering ◽  
Lasso Regression ◽  
Gene Expressions ◽  
Tumor Tissues ◽  
Cancer Genome Atlas ◽  
Selection Operator ◽  
Cox Analysis

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death. Among these, lung adenocarcinoma (LUAD) accounts for most cases. Due to the improvement of precision medicine based on molecular characterization, the treatment of LUAD underwent significant changes. With these changes, the prognosis of LUAD becomes diverse. N6-methyladenosine (m6A) is the most predominant modification in mRNAs, which has been a research hotspot in the field of oncology. Nevertheless, little has been studied to reveal the correlations between the m6A-related genes and prognosis in LUAD. Thus, we conducted a comprehensive analysis of m6A-related gene expressions in LUAD patients based on The Cancer Genome Atlas (TCGA) database by revealing their relationship with prognosis. Different expressions of the m6A-related genes in tumor tissues and non-tumor tissues were confirmed. Furthermore, their relationship with prognosis was studied via Consensus Clustering Analysis, Principal Components Analysis (PCA), and Least Absolute Shrinkage and Selection Operator (LASSO) Regression. Based on the above analyses, a m6A-based signature to predict the overall survival (OS) in LUAD was successfully established. Among the 479 cases, we found that most of the m6A-related genes were differentially expressed between tumor and non-tumor tissues. Six genes, HNRNPC, METTL3, YTHDC2, KIAA1429, ALKBH5, and YTHDF1 were screened to build a risk scoring signature, which is strongly related to the clinical features pathological stages (p<0.05), M stages (p<0.05), T stages (p < 0.05), gender (p=0.04), and survival outcome (p=0.02). Multivariate Cox analysis indicated that risk value could be used as an independent prognostic factor, revealing that the m6A-related genes signature has great predictive value. Its efficacy was also validated by data from the Gene Expression Omnibus (GEO) database.

scholarly journals Kinesin Family Member 18A (KIF18A) Contributes to the Proliferation, Migration, and Invasion of Lung Adenocarcinoma Cells In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Fu-Tao Chen ◽  
Fu-Kuan Zhong
Keyword(s):  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Clinical Stage ◽  
Migration And Invasion ◽  
Expression Levels ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Tumor Growth And Metastasis

Objective. To determine the expression levels of KIF18A in lung adenocarcinoma and its relationship with the clinicopathologic features of patients undergoing radical colectomy and explore the potential role in the progression of lung adenocarcinoma. Methods. Immunohistochemical assays were performed to explore the expression levels of KIF18A in 82 samples of lung adenocarcinoma and corresponding normal tissues. According to the levels of KIF18A expression in lung adenocarcinoma tissue samples, patients were classified into the KIF18A high expression group and low expression group. Clinical data related to the perioperative clinical features (age, gender, smoking, tumor size, differentiation, clinical stage, and lymph node metastasis), the potential correlation between KIF18A expression levels, and clinical features were analyzed, and the effects of KIF18A on lung adenocarcinoma cell proliferation, migration, and invasion were measured by colony formation assay, MTT assay, wound healing assay, and transwell assays. The possible effects of KIF18A on tumor growth and metastasis were measured in mice through tumor growth and tumor metastasis assays in vivo. Results. KIF18A in lung adenocarcinoma tissues. Further, KIF18A was significantly associated to clinical characteristic features including the tumor size (P=0.033) and clinical stage (P=0.041) of patients with lung adenocarcinoma. Our data also investigated that KIF18A depletion dramatically impairs the proliferation, migration, and invasion capacity of lung adenocarcinoma cells in vitro and inhibits tumor growth and metastasis in mice. Conclusions. Our study reveals the involvement of KIF18A in the progression and metastasis of lung adenocarcinoma and provides a novel therapeutic target for the treatment of lung adenocarcinoma.

scholarly journals Abnormally expressed JunB transactivated by IL-6/STAT3 signaling promotes uveal melanoma aggressiveness via epithelial–mesenchymal transition

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Chaoju Gong ◽  
Jie Shen ◽  
Zejun Fang ◽  
Lei Qiao ◽  
Ruifang Feng ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Transcriptional Level ◽  
Mesenchymal Transition ◽  
Stat3 Signaling ◽  
Epithelial Marker ◽  
Cancer Genome Atlas

Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and it carries a high risk of metastasis and mortality. Various proinflammatory cytokines have been found to be significantly increased in the aqueous humor or vitreous fluid of UM patients; however, the role of these cytokines in UM metastasis remains elusive. In the present study, we found that long-term interleukin (IL)-6 exposure promoted the migration and invasion of UM cells, diminished cell–cell adhesion, and enhanced focal adhesion. Moreover, IL-6 treatment decreased the membranous epithelial marker TJP1 and increased the cytoplasmic mesenchymal marker Vimentin. Further investigation demonstrated that JunB played a critical role in IL-6-induced UM epithelial–mesenchymal transition (EMT). In UM cells, the expression of JunB was significantly up-regulated during the IL-6-driven EMT process. Additionally, JunB induction occurred at the transcriptional level in a manner dependent on phosphorylated STAT3, during which activated STAT3 directly bound to the JunB promoter. Importantly, the knockdown of STAT3 prevented the IL-6-induced EMT phenotype as well as cell migration and invasion, whereas JunB overexpression recovered the attenuated aggressiveness of UM cells. Similarly, with IL-6 stimulation, the stable overexpression of JunB strengthened the migratory and invasive capabilities of UM cells and induced the EMT-promoting factors (Snail, Twist1, matrix metalloproteinase (MMP)-2, MMP-14, and MMP-19). Analysis of The Cancer Genome Atlas (TCGA) database indicated that JunB was positively correlated with IL-6 and STAT3 in UM tissues. The present study proposes an IL-6/STAT3/JunB axis leading to UM aggressiveness by EMT, which illustrates the negative side of inflammatory response in UM metastasis.

scholarly journals Overexpression of CLEC18B Associates With the Proliferation, Migration, and Prognosis of Glioblastoma

ASN NEURO ◽  
2018 ◽  
Vol 10 ◽  
pp. 175909141878194 ◽  
Author(s):  
Rui-Ming Guo ◽  
Cheng-Bin Zhao ◽  
Peng Li ◽  
Liang Zhang ◽  
Su-Hua Zang ◽  
...  
Keyword(s):  
Inverse Correlation ◽  
The Cancer Genome Atlas ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Lectin Domain ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
Interfering Rna

C-type lectin domain family 18 member B (CLEC18B), encoding a superfamily of CLEC, has been found to be expressed in some of cancer cells, which possibly indicates it associated with cancer. However, the defined functional characterizations of CLEC18B in glioblastoma multiforme (GBM) progression still remain unclear. To this end, clinical relevance of CLEC18B expression with GBM patients’ prognosis was analyzed both in The Cancer Genome Atlas dataset of 174 tissues and 40 GBM tumor tissues collected from our hospital by using the Kaplan–Meier survival and the Cox proportional hazard model. The role of CLEC18B in GBM was determined by loss-of-function assay using small interfering RNA approach in vitro. Functional and signaling analyses were also performed to understand how CLEC18B facilitated the aggressiveness of GBM at molecular and cellular levels using Cell Counting Kit-8 assay, wound-healing, transwell, and Western blot analyses. Results from our analyses showed that CLEC18B was markedly elevated in both GBM tissues and cells, and exhibited strong inverse correlation with overall survival in GBM patients. Moreover, CLEC18B was identified as an independent predictor of patient survival. Functionally, knockdown of CLEC18B inhibited the growth, migration, and invasion of GBM cells. Mechanistic studies revealed that silencing of CLEC18B resulted in downregulation of Wnt/β-catenin signaling activity. Collectively, our findings provide clinical, molecular, and cellular evidence of CLEC18B as a promising prognostic biomarker and therapeutic target for GBM.

Sign in / Sign up

Export Citation Format

Share Document