scholarly journals HMGA1-Regulating microRNAs Let-7a and miR-26a are Downregulated in Human Seminomas

2020 ◽  
Vol 21 (8) ◽  
pp. 3014 ◽  
Author(s):  
Marco De Martino ◽  
Francesco Esposito ◽  
Simona Pellecchia ◽  
Ricardo Cortez Cardoso Penha ◽  
Gerardo Botti ◽  
...  
Keyword(s):  
Cell Line ◽  
Critical Role ◽  
Germ Cell Tumors ◽  
Inverse Correlation ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Testicular Germ Cell ◽  
Functional Studies ◽  
Hmga1 Expression ◽  
Cancer Genome Atlas

Background: Recent studies have underlined HMGA protein’s key role in the onset of testicular germ cell tumors, where HMGA1 is differently expressed with respect to the state of differentiation, suggesting its fine regulation as master regulator in testicular tumorigenesis. Several studies have highlighted that the HMGA1 transcript is strictly regulated by a set of inhibitory microRNAs. Thus, the aim of this study is to test whether HMGA1 overexpression in human seminomas may be induced by the deregulation of miR-26a and Let-7a—two HMGA1-targeting microRNAs. Methods: HMGA1 mRNA and Let-7a and miR-26a levels were measured in a seminoma dataset available in the Cancer Genome Atlas database and confirmed in a subset of seminomas by qRT-PCR and western blot. A TCam-2 seminoma cell line was then transfected with Let-7a and miR-26a and tested for proliferation and motility abilities. Results: an inverse correlation was found between the expression of miR-26a and Let-7a and HMGA1 expression levels in seminomas samples, suggesting a critical role of these microRNAs in HMGA1 levels regulation. Accordingly, functional studies showed that miR-26a and Let-7a inhibited the proliferation, migration and invasion capabilities of the human seminoma derived cell line TCam-2. Conclusions: these data strongly support that the upregulation of HMGA1 levels occurring in seminoma is—at least in part—due to the downregulation of HMGA1-targeting microRNAs.

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.

LncRNA ELFN1-AS1 promotes esophageal cancer progression by up-regulating GFPT1 via sponging miR-183-3p

2020 ◽  
Vol 401 (9) ◽  
pp. 1053-1061 ◽  
Author(s):  
Chunyan Zhang ◽  
Hongkai Lian ◽  
Linsen Xie ◽  
Ningwei Yin ◽  
Yuanbo Cui
Keyword(s):  
Esophageal Cancer ◽  
Cancer Progression ◽  
Critical Role ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Over Expression ◽  
Fibronectin Type Iii ◽  
Cancer Genome Atlas ◽  
Fibronectin Type Iii Domain

AbstractAccumulating studies highlight the critical role of long non-coding RNAs (lncRNAs) in the development of various human cancers. Extracellular leucine rich repeat and fibronectin type III domain containing 1-antisense RNA 1 (ELFN1-AS1) was shown to be a newly found lncRNA that abnormally expressed in human tumors. However, till now the specific function of this lncRNA in esophageal cancer (ESCA) remains unknown. In this study, we discovered that higher ELFN1-AS1 expression indicated shorter patient survival in pan-cancer, including ESCA, using online The Cancer Genome Atlas (TCGA) tools. The lncRNA ELFN1-AS1 was significantly up-regulated in ESCA tissues and cell lines when compared with the counterparts. Down-regulation of ELFN1-AS1 restrained cell proliferation, migration, and invasion of ESCA in vitro. In addition, we found that the expression of microRNA-183-3p (miR-183-3p) and ELFN1-AS1 or glutamine-fructose-6-phosphate transaminase 1 (GFPT1) were inversely correlated in ESCA. Both ELFN1-AS1 and GFPT1 are direct targets of miR-183-3p in ESCA. The effects of ELFN1-AS1 knockdown on ESCA progression were partially rescued by inhibition of miR-183-3p or over-expression of GFPT1. In summary, the results of this study suggest that the lncRNA ELFN1-AS1 facilitates the progression of ESCA by acting as a competing endogenous RNA (ceRNA) to promote GFPT1 expression via sponging miR-183-3p.

scholarly journals Krüppel-Like Factor 7 is a Marker of Aggressive Gastric Cancer and Poor Prognosis

2017 ◽  
Vol 43 (3) ◽  
pp. 1090-1099 ◽  
Author(s):  
Zhonghua Jiang ◽  
Tingting Yu ◽  
Zhining Fan ◽  
Hongmei Yang ◽  
Xin Lin
Keyword(s):  
Gastric Cancer ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Strong Negative Correlation ◽  
Functional Studies ◽  
Expression Of Genes ◽  
Cancer Genome Atlas

Background/Aims: Krüppel-like factor (KLF) 7 protein is a member of the KLF transcription factor family, which plays important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation and metabolism. However, the role of KLF7 in gastric cancer (GC) is unknown. The aim of this study is to explore the role of KLF7 in GC and its correlation with clinicopathological characteristics and prognosis of GC patients. Methods: We first systematically evaluated dysregulation of the KLF family in The Cancer Genome Atlas (TCGA) GC database. Then, 252 patients who underwent surgery for GC were enrolled to validate the results from the TCGA. Functional studies were also used to explore the role of KLF7 in GC. Results: In the TCGA database, we found that KLF7 was an independent predictor for survival by both univariate and multivariate analysis (P<0.05). In a validation cohort, KLF7 expression was significantly increased in GC tissues compared with adjacent normal controls (P=0.013). High KLF7 expression correlated with inferior prognostic factors, such as T stage (P=0.022), N stage (P =0.005) and lymphovascular invasion (P=0.009). Furthermore, we observed a strong negative correlation between KLF7 expression and 5-year overall survival and disease-free survival in GC patients (P<0.05). Moreover, our in vitro studies showed a notable decrease in migration in KLF7 knockdown cells. Conclusion: KLF7 has an important role in GC progression, as it inhibits GC cell migration and may serve as a prognostic marker.

scholarly journals Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad Signaling

2020 ◽  
Vol 7 ◽  
Author(s):  
Changshui Zhuang ◽  
Ying Liu ◽  
Shengqiang Fu ◽  
Chaobo Yuan ◽  
Jingwen Luo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Line ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Pathological Process ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion

A subset of long non-coding RNAs (lncRNAs), categorized as miRNA-host gene lncRNAs (lnc-miRHGs), is processed to produce miRNAs and involved in cancer progression. This work aimed to investigate the influences and the molecular mechanisms of lnc-miRHGs MIR497HG in bladder cancer (BCa). The miR-497 and miR-195 were derived from MIR497HG. We identified that lnc-miRHG MIR497HG and two harbored miRNAs, miR-497 and miR-195, were downregulated in BCa by analyzing The Cancer Genome Atlas and our dataset. Silencing of MIR497HG by CRISPR/Cas13d in BCa cell line 5637 promoted cell growth, migration, and invasion in vitro. Conversely, overexpression of MIR497HG suppressed cell progression in BCa cell line T24. MiR-497/miR-195 mimics rescued significantly the oncogenic roles of knockdown of MIR497HG by CRISPR/Cas13d in BCa. Mechanistically, miR-497 and miR-195 co-ordinately suppressed multiple key components in Hippo/Yap and transforming growth factor β signaling and particularly attenuated the interaction between Yap and Smad3. In addition, E2F4 was proven to be critical for silencing MIR497HG transcription in BCa cells. In short, we propose for the first time to reveal the function and mechanisms of MIR497HG in BCa. Blocking the pathological process may be a potential strategy for the treatment of BCa.

scholarly journals Distinct telomere length and molecular signatures in seminoma and non-seminoma of testicular germ cell tumor

2018 ◽  
Vol 20 (4) ◽  
pp. 1502-1512 ◽  
Author(s):  
Hua Sun ◽  
Pora Kim ◽  
Peilin Jia ◽  
Ae Kyung Park ◽  
Han Liang ◽  
...  
Keyword(s):  
Germ Cell ◽  
Telomere Length ◽  
Complex Disease ◽  
Expression Profiles ◽  
Germ Cell Tumors ◽  
Telomerase Activity ◽  
The Cancer Genome Atlas ◽  
Testicular Germ Cell ◽  
Telomere Elongation ◽  
Yamanaka Factors

AbstractTesticular germ cell tumors (TGCTs) are classified into two main subtypes, seminoma (SE) and non-seminoma (NSE), but their molecular distinctions remain largely unexplored. Here, we used expression data for mRNAs and microRNAs (miRNAs) from The Cancer Genome Atlas (TCGA) to perform a systematic investigation to explain the different telomere length (TL) features between NSE (n = 48) and SE (n = 55). We found that TL elongation was dominant in NSE, whereas TL shortening prevailed in SE. We further showed that both mRNA and miRNA expression profiles could clearly distinguish these two subtypes. Notably, four telomere-related genes (TelGenes) showed significantly higher expression and positively correlated with telomere elongation in NSE than SE: three telomerase activity-related genes (TERT, WRAP53 and MYC) and an independent telomerase activity gene (ZSCAN4). We also found that the expression of genes encoding Yamanaka factors was positively correlated with telomere lengthening in NSE. Among them, SOX2 and MYC were highly expressed in NSE versus SE, while POU5F1 and KLF4 had the opposite patterns. These results suggested that enhanced expression of both TelGenes (TERT, WRAP53, MYC and ZSCAN4) and Yamanaka factors might induce telomere elongation in NSE. Conversely, the relative lack of telomerase activation and low expression of independent telomerase activity pathway during cell division may be contributed to telomere shortening in SE. Taken together, our results revealed the potential molecular profiles and regulatory roles involving the TL difference between NSE and SE, and provided a better molecular understanding of this complex disease.

scholarly journals ITGA3 Is a Reliable Biomarker and Putative Therapeutic Target for Glioma

2020 ◽  
Author(s):  
Qing Zhang ◽  
Chen Zhu ◽  
Gefei Guan ◽  
Shuai Shen ◽  
Yunhe Han ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Glioma Cells ◽  
The Cancer Genome Atlas ◽  
Integrin Subunit ◽  
Central Nervous System Tumor ◽  
Mesenchymal Transition ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract Background: Glioma is the most prevalent and malignant primary central nervous system tumor in adults. As a member of the integrin alpha chain family of proteins, integrin subunit alpha 3 (ITGA3) has been found to play a critical role in the occurrence and progression of several cancers, including lung, ovarian, and pancreatic cancers. However, the role of ITGA3 in glioma remains unclear.Methods: The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), REMBRANDT, GSE16011, GSE59612, and GSE4290 datasets were used to analyze relevant characteristics of ITGA3 in glioma. R language and GraphPad Prism 7.00 were employed as major tools for statistical analysis and graph manipulation.Results: We identified that ITGA3 expression was upregulated in glioma and related to unfavorable outcomes of glioma patients. Expression of ITGA3 also tended to be enriched in aggressive subtypes of glioma. We demonstrated that expression of ITGA3 was negatively correlated with glioma purity. In gliomas with high ITGA3 expression, the anti-glioma immune response was inhibited. ITGA3 also regulated angiogenesis within the glioma microenvironment and promoted the epithelial–mesenchymal transition (EMT) and autophagy of glioma cells. GSEA analysis revealed that ITGA3 could activate ERK1/2 and PI3K/AKT/mTOR pathways.Conclusion: Our data suggested that ITGA3 promoted the malignant progression of glioma by regulating the immunity of glioma as well as the EMT and autophagy of glioma cells, which could act as a therapeutic target for glioma.

scholarly journals Downregulation of the FBXO43 gene inhibits tumor growth in human breast cancer by limiting its interaction with PCNA

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Rulan Ma ◽  
Kun Zhu ◽  
Dawei Yuan ◽  
Meijun Gong ◽  
Yijun Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Bioinformatics Analysis ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Human Breast ◽  
Cancer Genome Atlas ◽  
Proliferation Assays ◽  
Proliferative Ability

Abstract Background The function and regulatory mechanism of FBXO43 in breast cancer (BC) are still unclear. Here, we intended to determine the role and mechanism of FBXO43 in BC. Methods FBXO43 expression in BC was evaluated by analysis of The Cancer Genome Atlas (TCGA). RT-qPCR and western blotting were utilized to detect FBXO43 expression in BC cell lines. Lentivirus was applied to downregulate FBXO43 in human BC cells. Proliferation assays were performed to evaluate the proliferative ability of BC cells. The apoptosis and cell cycle analysis of BC cells were analyzed by flow cytometry. Cell migration and invasion were investigated via Transwell assays. The function of FBXO43 in vivo was evaluated by constructing a xenograft mouse model. The proteins that might interact with FBXO43 in BC were identified by mass spectrometry, bioinformatics analysis, and co-immunoprecipitation (Co-IP) assays. Finally, rescue experiments were conducted to validate the recovery effects of the proteins interacting with FBXO43. Results FBXO43 was highly expressed in BC and was significantly downregulated after FBXO43 knockdown. The proliferation, migration, and invasion of BC cells were inhibited, and cell apoptosis was induced by FBXO43 knockdown. In addition, an in vivo experiment indicated that FBXO43 knockdown could inhibit the cell growth of BC. The results of the Co-IP assay showed that FBXO43 interacted with PCNA. Further rescue experiments confirmed that overexpression of PCNA significantly reversed the effects of FBXO43 knockdown on BC cells. Conclusion Downregulation of FBXO43 inhibits the tumor growth of BC by limiting its interaction with PCNA. FBXO43 might be a new potential oncogene and a therapeutic target for BC.

scholarly journals Nuclear Localization of PTTG1 Promotes Migration and Invasion of Seminoma Tumor Through Activation of MMP-2.

2020 ◽  
Author(s):  
Emanuela Teveroni ◽  
Fiorella Di Nicuolo ◽  
Giada Bianchetti ◽  
Alan L. Epstein ◽  
Giuseppe Grande ◽  
...  
Keyword(s):  
Subcellular Localization ◽  
Cell Lines ◽  
Nuclear Localization ◽  
Germ Cell Tumors ◽  
Causal Link ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Testicular Germ Cell ◽  
Matrigel Invasion

Abstract Background: Seminoma is the most common subtype of testicular germ cell tumors (TGCTs) and its molecular patterns have not been fully clarified. The pituitary tumor-transforming gene 1 (PTTG1) is a securin, inhibitor of premature sister chromatid segregation during mitosis and is overexpressed in many cancers. PTTG1 shows the ability to sustain the invasiveness of several cancer types through its transcriptional activity. In the present study, we investigate the PTTG1 role on the invasive properties of seminoma.Methods: Three seminoma cell lines showing different proliferation rates and marker expression features were used as an in vitro model. Biochemical and immunofluorescence analyses were performed to evaluate PTTG1 levels and subcellular localization. Functional analyses, including wound healing, matrigel invasion assays and zymography were applied to study migratory and invasive capability of the cell lines. RNA interference studies and overexpression experiments were performed to address the PTTG1 role in seminoma cell lines invasiveness. Finally, the Atlas database was interrogated to study PTTG1 subcellular localization in seminoma and non-seminomas testicular tumors in order to analyze the PTTG1 and matrix metalloproteinase-2 (MMP-2) levels in these groups.Results: We found that PTTG1 was highly and differentially expressed in the seminoma cell lines. PTTG1 nuclear localization was positively correlated to the aggressive phenotype. Modulation of PTTG1 expression uncovered a direct causal link between PTTG1 and seminoma cell line invasiveness. Importantly, analysis of the human Atlas database revealed that PTTG1 was localized in the nucleus exclusively in seminoma compared with non-seminoma tumors and showed that MMP-2 levels was significant higher in seminomas.Conclusions: The results of the present research elucidate the role of nuclear PTTG1 in promoting invasiveness and metastatic process of seminoma cell lines. Analysis from the Atlas database strongly supported these results, revealing an exclusive PTTG1 nuclear localization and an increase of MMP-2 levels in seminoma versus non-seminoma tumors. Overall, these data lead to the hypothesis that nuclear PTTG1 is an eligible prognostic factor in seminomas.

scholarly journals ATG101 as a Novel Prognostic Biomarker Related to Immunotherapy in Pan-cancer

2021 ◽  
Author(s):  
Zijian Zhang ◽  
Jinggang Mo ◽  
Chong Jin ◽  
Hao Jiang ◽  
Zhongtao Liu ◽  
...  
Keyword(s):  
Critical Role ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Integrated Analysis ◽  
Tumour Immunity ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
The Relationship ◽  
Pan Cancer

Abstract Background: ATG101 plays a significant role in the occurrence and development of tumours by regulating autophagy. Our study aimed to research the correlation between the expression of ATG101 and tumour prognosis and its role in tumour immunity. Methods: First, integrated analysis of The Cancer Genome Atlas and Genotype-Tissue Expression portals were used to analyse the expression of ATG101. Then, we used Kaplan–Meier curves for survival analysis. Next, we analysed the relationship between ATG101 expression and six immune cells, the immune microenvironment and immune checkpoints. Besides, we analysed the relationship between the expression of ATG101 and methyltransferase. Finally, we used GSEA to study the function of ATG101 in COAD and LIHC. Results: Integrated analysis showed that ATG101 was overexpressed in different tumours. Kaplan–Meier curves found that ATG101 was associated with poor prognosis in most tumours. We found that that ATG101 can be used as a target and prognostic marker of tumour immunotherapy for different tumours. We also found that ATG101 regulates DNA methylation. GSEA analysis showed that ATG101 may play a critical role in COAD and LIHC.Conclusions: Our study highlights the significance of ATG101 in the study of tumour immunity from a pan-cancer perspective.

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