ALKBH4 promotes tumourigenesis with a poor prognosis in non-small-cell lung cancer

AbstractThe human AlkB homolog family (ALKBH) of proteins play a critical role in some types of cancer. However, the expression and function of the lysine demethylase ALKBH4 in cancer are poorly understood. Here, we examined the expression and function of ALKBH4 in non-small-cell lung cancer (NSCLC) and found that ALKBH4 was highly expressed in NSCLC, as compared to that in adjacent normal lung tissues. ALKBH4 knockdown significantly induced the downregulation of NSCLC cell proliferation via cell cycle arrest at the G1 phase of in vivo tumour growth. ALKBH4 knockdown downregulated E2F transcription factor 1 (E2F1) and its target gene expression in NSCLC cells. ALKBH4 and E2F1 expression was significantly correlated in NSCLC clinical specimens. Moreover, patients with high ALKBH4 expression showed a poor prognosis, suggesting that ALKBH4 plays a pivotal tumour-promoting role in NSCLC.

Download Full-text

Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000488166 ◽

2018 ◽

Vol 45 (6) ◽

pp. 2213-2224 ◽

Cited By ~ 19

Author(s):

Meng Zhao ◽

Yahui Liu ◽

Ran Liu ◽

Jin Qi ◽

Yongwang Hou ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Small Cell ◽

Small Cell Lung ◽

Mesenchymal Transition

Background/Aims: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11’s role in NSCLC and the detailed mechanism behind it. Methods: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial–mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. Results: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial–mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. Conclusions: Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.

Download Full-text

Expression and function of the insulin-like growth factor I system in human non-small-cell lung cancer and normal lung cell lines

International Journal of Cancer ◽

10.1002/ijc.2910560618 ◽

1994 ◽

Vol 56 (6) ◽

pp. 858-866 ◽

Cited By ~ 35

Author(s):

Roberto E. Favoni ◽

Alessandra De Cupis ◽

Federica Ravera ◽

Claudia Cantoni ◽

Paolo Pirani ◽

...

Keyword(s):

Lung Cancer ◽

Growth Factor ◽

Small Cell Lung Cancer ◽

Cell Lines ◽

Cell Lung Cancer ◽

Small Cell ◽

Normal Lung ◽

Small Cell Lung ◽

Factor I ◽

And Function

Download Full-text

Cross-Species Functional Analysis of Cancer-Associated Fibroblasts Identifies a Critical Role for CLCF1 and IL-6 in Non–Small Cell Lung Cancer In Vivo

Cancer Research ◽

10.1158/0008-5472.can-12-1097 ◽

2012 ◽

Vol 72 (22) ◽

pp. 5744-5756 ◽

Cited By ~ 52

Author(s):

Silvestre Vicent ◽

Leanne C. Sayles ◽

Dedeepya Vaka ◽

Purvesh Khatri ◽

Olivier Gevaert ◽

...

Keyword(s):

Lung Cancer ◽

Functional Analysis ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Critical Role ◽

Small Cell ◽

Cancer Associated Fibroblasts ◽

Small Cell Lung

Download Full-text

Effect of friend leukemia virus integration 1 on tumorigenesis of small cell lung cancer cells and activation of the miR-17-92 pathway.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20015 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20015-e20015

Author(s):

Jiuwei Cui ◽

Lingyu Li ◽

Wei Song ◽

Jifan Hu ◽

Wei Li ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Leukemia Virus ◽

Small Cell ◽

Normal Lung ◽

Small Cell Lung ◽

Friend Leukemia ◽

Virus Integration

e20015 Background: Small cell lung cancer (SCLC) is regarded as the most devastative type of human lung malignancies, mostly due to their rapid and disseminated growth pattern. However, the molecular factors that drive rapid progression of SCLC remain unclear. Friend leukemia virus integration 1( FLI1),an Ets transcription factor family member, was identified as a proto-oncogene in some tumors via regulation of different target genes. In this study, we explored the potential role of FLI1 in SCLC. Methods: FLI1 protein expression was evaluated by immunohistochemistry in 67 primary SCLC, 20 non-small cell lung cancer (NSCLC) and 20 normal lung specimens. Correlation between FLI1 expression and clinical characteristics was evaluated with the logistic regression. Cell proliferation, cell cycle, apoptosis, colony formation assays in vitro and tumorigenesis assay in vivo were used to explore the function of FLI1 in SCLC cells. Use the miR-17-92 promoter/luciferase reporter assay to identify the regulation of FLI1 on miR-17-92 cluster promoter. Results: Immunohistochemical staining data showed that FLI1 was significantly upregulated in SCLC tissues compared to that in NSCLC and normal lung tissues ( p< 0.01). The expression score of FLI1 oncoprotein was associated with the extensive stage of SCLC and the overexpressed Ki67. Knockdown of FLI1 promoted apoptosis and induced repression of cell proliferation, tumor colony formation and in vivo tumorigenicity in highly aggressive SCLC cell lines. Importantly, we discovered that FLI1 promoted tumorigenesis by activating the miR-17-92 cluster family transcritption. Conclusions: This study uncovers that FLI1 is an important driving factor that promotes tumor growth in SCLC through the miR-17-92 pathway, and may serve as an attractive target for therapeutic intervention of SCLC.

Download Full-text

α,1,6-Fucosyltransferase (FUT8) regulates cancer-promoting capacities of cancer-associated fibroblasts (CAFs) through the modification of EGFR core fucosylation in non-small cell lung cancer

10.21203/rs.2.18620/v1 ◽

2019 ◽

Author(s):

Fengzhou Li ◽

Shilei Zhao ◽

Yanwei Cui ◽

Jiaqi Qiang ◽

Tao Guo ◽

...

Keyword(s):

Lung Cancer ◽

Tumor Microenvironment ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Normal Lung ◽

Cancer Associated Fibroblasts ◽

Small Cell Lung ◽

Nsclc Patients

Abstract BackgroundCancer-associated fibroblasts (CAFs), the main component of the tumor microenvironment (TME) of NSCLC, are activated by phenotypic transformation into myofibroblasts. α,1,6-fucosyltransferase (FUT8), the key enzyme catalyzing core α,1,6-fucosylation (CF), plays important roles in multiple malignancies. In the current study, we investigated the functions and mechanism of CF mediated by FUT8 in CAFs in NSCLC through bioinformatics analysis, retrospective clinical studies and in vitro/in vivo laboratory experiments.MethodsBioinformatics was used to reveal the relationship between FUT8 and CAFs. Resected specimens, clinical data and prognostic information from 135 NSCLC patients were analyzed to assess the prognostic value of FUT8 in CAFs. Primary CAFs and normal lung fibroblasts were extracted from NSCLC patients and cocultured with NSCLC cell lines in a novel noncontact coculture device produced by 3D printing. In vivo, CAF/NSCLC coinjection tumorigenesis assay was performed in nude mice to study the function of FUT8/CF in TME. The mechanisms of FUT8/CF in CAFs regulating the cocultured NSCLC cells were investigated in cell and molecular experiments. ResultsFUT8 in CAFs is an independent risk factor for prognosis. FUT8/CF in CAFs is essential for CAFs to maintain their ability to promote NSCLC. FUT8/CF in CAFs is responsible for the cancer-promoting capacities of CAFs and lead to a malignant tumor microenvironment. CF modification enhances tyrosine phosphorylation of EGFR in CAFs, which causes activation of downstream signalings of EGFR and maintains cancer-promoting properties of CAFs.ConclusionFUT8 regulates cancer-promoting capacities of CAFs via the modification of EGFR CF in non-small cell lung cancer.

Download Full-text

LIFE SPAN PREDICTION AT METASTATIC NON-SMALL CELL LUNG CANCER

Problems in oncology ◽

10.37469/0507-3758-2018-64-4-522-527 ◽

2018 ◽

Vol 64 (4) ◽

pp. 522-527

Author(s):

Aleksey Shutko ◽

Viktor Mus

Keyword(s):

Lung Cancer ◽

Stem Cells ◽

Small Cell Lung Cancer ◽

Life Span ◽

Cell Lung Cancer ◽

Poor Prognosis ◽

Small Cell ◽

Hemopoietic Stem Cells ◽

Small Cell Lung ◽

Individual Life

Individual parameters of circulating hemopoietic stem cells (HSC) lymphoid origin were measured by cytofluorometry before treatment of patients with metastatic non-small cell lung cancer and were retrospectively compared with individual life span's (LS). The possibility of poor prognosis of treatment's results (LS

Download Full-text

The Key microRNAs Regulated the Development of Non-small Cell Lung Cancer by Targeting TGF-β-induced epithelial–mesenchymal Transition

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190410151945 ◽

2019 ◽

Vol 22 (4) ◽

pp. 238-244 ◽

Cited By ~ 2

Author(s):

Gang Chen ◽

Bo Ye

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lines ◽

Cell Lung Cancer ◽

Small Cell ◽

Nsclc Cell ◽

Normal Lung ◽

Migration And Invasion ◽

Small Cell Lung ◽

Mesenchymal Transition

Purpose: Epithelial-to-Mesenchymal Transition (EMT) was reported to play a key role in the development of Non-Small Cell Lung Cancer (NSCLC). The process of EMT is regulated by the changes of miRNAs expression. However, it is still unknown which miRNA changed the most in the process of canceration and whether these changes played a role in tumor development. Methods: A total of 36 SCLC patients treated in our hospital between 11th, 2015 and 10th, 2017 were enrolled. The samples of cancer tissues and paracancer tissues of patients were collected and analyzed. Then, the miRNAs in normal lung cells and NSCLC cells were also analyzed. In the presence of TGF-β, we transfected the miRNA mimics or inhibitor into NSCLC cells to investigate the role of the significantly altered miRNAs in cell migration and invasion and in the process of EMT. Results: MiR-330-3p was significantly up-regulated in NSCLC cell lines and tissues and miRNA- 205 was significantly down-regulated in NSCLC cell lines and NSCLC tissues. Transfected miRNA-205 mimics or miRMA-330-3p inhibitor inhibited the migration and invasion of NCIH1975 cell and restrained TGF-β-induced EMT in NSCLC cells. Conclusion: miRNA-330-3p and miRNA-205 changed the most in the process of canceration in NSCLC. Furthermore, miR-330-3p promoted cell invasion and metastasis in NSCLC probably by promoting EMT and miR-205 could restrain NSCLC likely by suppressing EMT.

Download Full-text