scholarly journals TNFAIP3 Suppresses Lung Cancer Progression via Regulating Cell Proliferation and Apoptosis

2020 ◽  
Author(s):  
Han Chen ◽  
Jie Gao ◽  
Yongsheng Yu ◽  
Qian Zhou ◽  
Shan yongqi
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Colony Formation ◽  
The Cancer Genome Atlas ◽  
Lung Cancer Cells ◽  
Protein Levels ◽  
Cancer Tissues

Abstract Background: The ubiquitin-editing enzyme TNF inducible protein 3 (TNFAIP3) is a crucial regulator of inflammation and immunity. It is also involved in tumorigenesis of various cancers such as lymphomas, colorectal tumors and breast cancer. In this study, we aimed to explore the role and regulatory mechanism of TNFAIP3 in lung cancer. Methods: The expression of TNFAIP3 was determined in the Cancer Genome Atlas (TCGA) database. The levels of TNFAIP3 in lung cancer tissues was determined by immunohistochemistry (IHC) assay. TNFAIP3 knockdown and overexpression were performed, followed by further evaluation of cell viability, cell cycle and apoptosis. Cell cycle and apoptosis were observed by using flow cytometry and the key regulatory proteins were detected by western blotting. Colony formation assessment and EdU assay were adopted to check cell proliferation. Results: TNFAIP3 expression was downregulated in lung cancer tissues at both mRNA and protein levels, comparing with that in adjacent non-tumor tissues. Consequently, the colony formation ability of lung cancer cells was enhanced, and the number of EdU positive lung cancer cells was increased. By contrast, elevated TNFAIP3 expression resulted in decreased colony formation ability of lung cancer cells. Mechanistically, TNFAIP3 overexpression rendered cell cycle of lung cancer cells halted at G0/G1 phase and caused apoptosis of lung cancer cells.Conclusion: Our data suggested that TNFAIP3 exhibits tumor suppressive roles in lung cancer.

scholarly journals POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ronggang Luo ◽  
Yi Zhuo ◽  
Quan Du ◽  
Rendong Xiao
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Cancer Tissues

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

scholarly journals KLF8 overexpression promotes the growth of human lung cancer cells by promoting the expression of JMJD2A

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dongjie Ma ◽  
Hongsheng Liu ◽  
Yingzhi Qin ◽  
Zhenhuan Tian ◽  
Shanqing Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Colony Formation ◽  
Human Lung ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Small Cell Lung

Abstract Background Non-small-cell lung cancer (lung cancer) has become one of the leading causes worldwide and the underlying mechanism is not fully understood. The transcriptional factor Kruppel like factor 8 (KLF8) is involved in the initiation, progression, transformation, and metastasis of diverse cancers. However, the roles of KLF8 in human non-small cell lung cancer remain unknown. Methods CCK-8 kit and colony formation assay were performed to determine the cell growth of lung cancer cells. Flow cytometry analysis was used to evaluate apoptosis and cell cycle of lung cancer cells. Luciferase reporter assay was used to examine the activation of JMJD2A promoter by KLF8. Chromatin immunoprecipitation assay was performed to evaluate the binding of KLF8 to JMJD2A promoter. Western blot and polymerase chain reaction were applied to analyze the expression of interested genes. Results The mRNA and protein levels of KLF8 in human non-small cell lung cancer tissues were overexpressed compared with the non-cancer tissues. KLF8 was knocked down with lentivirus-mediated short-hairpin RNA (shRNA) in human lung cancer cells (A549 and H1299 cells). The phenotypic results showed that KLF8 knockdown decreased the proliferation rate and colony formation of lung cancer cells. By contrast, lentivirus-mediated KLF8 overexpression promoted the growth of lung cancer cells (A549 and H1299 cells) and non-cancerous bronchial epithelial cell line BEAS-2B. Next, we showed that KLF8 regulated cell cycle at the G0 phase but not regulates cellular apoptosis of lung cancer cells. KLF8 regulated the expression of the cell cycle regulators P21 and CDK4 in a JMJD2A-dependent manner and JMJD2A knockdown significantly blocked the functions of KLF8 in regulating cell cycle and proliferation of lung cancer cells. Finally, we observed that KLF8 bound the promoter of JMJD2A and facilitated the expression of JMJD2A. Conclusions Our evidence demonstrated that KLF8 upregulation in human lung cancer promotes the cell proliferation and colony formation of lung cancer cells. KLF8 binds to the promoter of JMJD2A and subsequently regulates the expression of P21 and CDK4, which contributes to the regulation of cell cycle by KLF8. KLF8 may serve as a target for the treatment of human lung cancer.

MiR-302a-3p, Sponged by HOXA-AS2, Suppresses Cell Proliferation and Invasion in Lung Cancer Cells

2019 ◽  
Vol 9 (12) ◽  
pp. 1644-1652
Author(s):  
Xueqin Pan ◽  
Dongchun Ma
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cell Apoptosis ◽  
Lung Cancer Cells ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion

Lung cancer is one of the most common malignant cancers with a poor survival rate and high mortality worldwide. MiRNAs have been evaluated as crucial regulators of human gene expression, and exerted vital role involved in cancer progression. MiR-302a-3p was aberrant expressed in cancers that include pancreatic cancer and hepatocellular cancer, but its biological role in lung cancer remains elusive. This study aimed to discover the role and potential mechanism of miR-302a-3p in lung cancer. The lung cancer cell line with the highest expression of miR-302a-3p was selected, which was then subjected to transfection of miR-302a-3p mimic. Quantitative RT-PCR was performed to detect gene expression. Western blot assay was performed to determine corresponding genes that related to cell proliferation, apoptosis and invasion. Cell Counting Kit (CCK)-8 assay, flow cytometry analysis, wound healing and Transwell assay were performed to detect cell proliferation, apoptosis, migration and invasion, respectively. Luciferase reporter assay was carried out to identify the targeting relationship of miR-302-3p and HOXA-AS2. MiR-302a-3p was downregulated in lung cancer cells, and overexpression of miR-302a-3p significantly suppressed cell proliferation, migration, invasion and promoted cell apoptosis. HOXA-AS2 was a direct target of miR-302a-3p and was regulated by miR-302a-3p. HOXA-AS2 was upregulated in lung cancer cells. Upregulated HOXA-AS2 could reverse the effect that overexpression of miR-302a-3p caused on cell proliferation, apoptosis, migration and invasion. Overall, miR-302a-3p exhibited anti-oncogenic activity by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis in lung cancer by targeting HOXA-AS2, disclosing the role and regulatory mechanism of miR-302a-3p, which provided a promising therapeutic target for the clinical application of lung cancer treatment.

scholarly journals LSR Promotes Cell Proliferation and Invasion in Lung Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Min Zhang ◽  
Cui Ma
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Biological Effects ◽  
The Cancer Genome Atlas ◽  
Lung Cancer Cells ◽  
Tumor Promoter ◽  
Migration And Invasion ◽  
Poor Prognostic Factor ◽  
Potential Biomarker

The lipolysis-stimulated lipoprotein receptor (LSR) displays an important regulatory role in cancer. However, the association between LSR and lung cancer is still elusive. Here, the candidate oncogene LSR on Ch.9q was obtained and assessed by bioinformatics analysis of The Cancer Genome Atlas (TCGA) dataset of lung cancer. We conducted clinical pathology and survival analysis based on the lung cancer database. We assessed the biological effects of LSR in lung cancer cells on cell proliferation. Our data indicated that LSR was upregulated in lung cancer cells. Meanwhile, LSR was identified in this study to be a poor prognostic factor, and its high expression exhibited relations with grades, stages, and nodal metastasis status. Using in vitro analysis, our data revealed that LSR could promote lung cancer progression by regulating cell proliferation, migration, and invasion. In our study, our data demonstrated that LSR was a tumor promoter for lung cancer and was a potential biomarker and target for lung cancer prognosis and treatment.

scholarly journals HMGB1 Promotes the Proliferation and Metastasis of Lung Cancer by Activating the Wnt/β-Catenin Pathway

2020 ◽  
Vol 19 ◽  
pp. 153303382094805 ◽  
Author(s):  
Xiao-hui Wang ◽  
Shu-ying Zhang ◽  
Mei Shi ◽  
Xiao-peng Xu
Keyword(s):  
Lung Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Colony Formation ◽  
Lung Cancer Cells ◽  
Mesenchymal Transition ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

The aim of this study was to investigate the role of high mobility group protein-1 (HMGB1) in the proliferation and migration of lung cancer cells. CCK-8 assays and colony formation assays were used to evaluate the effect of HMGB1 regulation on cancer cell viability and colony formation. Trans-well assays and wound healing assays were also performed. Our data showed that HMGB1 is upregulated in clinical lung cancer tissues compared with non-cancer tissues, and it is differentially expressed in lung cancer cell lines. The knockdown of HMGB1 in A549 lung cancer cells significantly reduced cell proliferation, viability and motility. In contrast, overexpression of HMGB1 in lung cancer H1299 cells significantly increased cell viability and motility. Western blotting showed that HMGB1 could promote epithelial-mesenchymal transition. The Wnt/β-catenin pathway was activated after overexpression of HMGB1 in H1299 cells, while it was inactivated by knocking down HMGB1 in A549 cells. These data suggest that HMGB1 promotes the proliferation and migration of lung cancer cells in vitro. The carcinogenic behavior of HMGB1 can be achieved by activating the Wnt/β-catenin pathway.

scholarly journals Cytoplasmic APE1 promotes lung cancer aggressiveness and cisplatin resistance via the COX-2/Akt/β-catenin signaling pathway

2020 ◽  
Author(s):  
Zhimin Zhang ◽  
Xiaojuan Lian ◽  
Xiaona Su ◽  
Maojun Liao ◽  
Chuan Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Clinical Effects ◽  
Cancer Aggressiveness ◽  
Cox 2 ◽  
Cancer Tissues

Abstract BACKGROUND Cisplatin is commonly used in lung cancer therapy, but cisplatin resistance in lung cancer cells remains an unsolved problem. Here, we report that cytoplasmic APE1 contributes to cisplatin resistance, cell proliferation and migration in lung cancer cells. METHODS Immunofluorescence, western blot analysis, lentivirus transfection and scratch assays, and transwell migration and invasion assays were carried out on the cell lines A549 and Calu-1. A total of 124 samples of lung cancer tissues were evaluated to determine the clinical effects of cytoplasmic APE1 and COX-2. RESULTS We found that cytoplasmic APE1 expression was lower in cisplatin sensitive cells than in cisplatin-resistant cells, and the upregulation of cytoplasmic APE1 significantly reduced cisplatin sensitivity in lung cancer cells. Gain-of-function studies demonstrated that cytoplasmic APE1 promoted lung cancer cell proliferation, migration and invasion in vitro and tumor growth in vivo, which were inhibited after cisplatin treatment. In patient samples, cytoplasmic APE1 in lung cancer tissues was an independent indicator of overall survive (OS) for lung cancer patients (P < 0.001). Mechanistic studies revealed that cytoplasmic APE1 promotes lung cancer malignancy by activating the COX-2/Akt/β-catenin pathway. Furthermore, the mutation of the APE1-C65 site caused upregulation of cytoplasmic APE1 and inhibited cell growth, migration and invasion of lung cancer cells. CONCLUSION We suggest that modulating cytoplasmic APE1 in lung cancer is a promising novel strategy for overcoming cisplatin resistance.

Peniciketal A, A Novel Spiroketal Compound, Exerts Anticancer Effects by Inhibiting Cell Proliferation, Migration and Invasion of A549 Lung Cancer Cells

2019 ◽  
Vol 18 (11) ◽  
pp. 1573-1581 ◽  
Author(s):  
Xue Gao ◽  
Yuming Zhou ◽  
Xiaoqi Zheng ◽  
Hongliu Sun ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Normal Fibroblast ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Anticancer Effects ◽  
A549 Lung

Background: Peniciketal A (Pe-A) is a spiroketal compound isolated from saline soil-derived fungus Penicillium raistrickii. However, its role for biological processes has not been clarified. In this study, we for the first time investigated the anticancer effects and the underlying mechanisms of Pe-A in A549 lung cancer cells. Metheds: Cell proliferation was tested by MTT assay and colony formation assay. Flow cytometry was performed to examine the cell cycle, apoptosis and mitochondrial membrane potential. Invasion and migration were analyzed using transwell assay and wound healing analysis. Immunofluorescence staining and western blotting were used to evaluate the protein expression. Results: Pe-A effectively inhibited proliferation, with IC50 values was 22.33 μM for 72 h. Mechanistic studies revealed that Pe-A caused cell cycle arrest at the G0-G1 phase by decreasing cyclinD1 expression and induced apoptosis through accelerating the mitochondrial apoptotic pathway. Moreover, Pe-A significantly inhibited A549 cell migration and invasion by reducing the protein levels of MMP-2 and MMP-9, while the Epithelial- Mesenchymal Transition (EMT) property was also changed. Importantly, Pe-A exhibited much lower toxicity towards L02, normal liver cells, and MRC5, normal fibroblast cells, compared to A549 cells. Conclusion: Collectively, the current results indicate that Pe-A may offer effective potentials and insights for lung cancer treatment and drug design.

scholarly journals Zebrafish xenograft model of human lung cancer for studying the function of LINC00152 in cell proliferation and invasion

2020 ◽  
Author(s):  
Wenyi Shen ◽  
Juan Pu ◽  
Jing Sun ◽  
Bing Tan ◽  
Wei Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cultured Cells ◽  
Human Cancer ◽  
Xenograft Model ◽  
Lung Cancer Cells ◽  
Proliferation And Invasion

Abstract Background: Numerous studies show that long non-coding RNAs take important roles in human cancer progression. Although zebrafish xenograft become a novel in vivo model for human cancer research recently, whether it can be used for studying the function of lncRNAs remains unknown.Methods: In vitro studies validated the roles of LINC00152 in the proliferation and invasion of lung cancer cells. In vivo studies by using zebrafish xenograft also confirmed these roles of LINC00152. In vivo confocal imaging was also used to evaluate the function of LINC00152 in cell proliferation and migration more accurately. Pharmacology experiments were further performed to study the potential tumor treatment of LINC00152 downregulation combined with EGFR inhibitor in cultured cells and zebrafish xenograft.Results: Silencing of LINC00152 suppressed cell proliferation and invasion in SPCA1 and A549 lung cancer cell lines in vitro . In zebrafish xenograft model, knockdown of LINC00152 reduced the proliferation and migration of lung cancer cells by two imaging methods at different magnification. Moreover, knocking-down LINC00152 enhanced the inhibition effect of afatinib for lung cancer progression in cultured cells and zebrafish xenograft model.Conclusion: Our study reveals the oncogenic roles and potential tumor treatment target of LINC00152 in lung cancer cells by zebrafish xenograft models, suggesting that this model could be used for the functional and application study of human lncRNA in tumor biology.* Wenyi Shen and Juan Pu contributed equally to this work.

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