scholarly journals The Human Positive Cofactor 4 is a Promising Chemotherapeutic Target in Lung Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Tianyu Sun ◽  
Jingge Zhang ◽  
Xiaoqing Fan ◽  
Tan Long ◽  
Shaolin Tao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Chemotherapy Resistance ◽  
Cell Sensitivity ◽  
Adenocarcinoma Cell ◽  
Cellular Processes ◽  
Upstream Regulator ◽  
Adenocarcinoma Cells ◽  
Multiple Drugs

Reduced sensitivity to chemotherapeutic drugs is almost inevitable in lung adenocarcinoma patients. Thus, understanding the relevant mechanisms is urgent. Positive cofactor 4 (PC4) was at first revealed to be a coactivator of basal transcription. Previous research has shown that PC4 participates in various cellular processes in normal and malignant cells. However, it is still unknown whether PC4 participates in altering the lung adenocarcinoma cell sensitivity to chemotherapy, and the relevant mechanisms remain to be explained. In this study, we discovered that PC4 was overexpressed in cisplatin-resistant lung adenocarcinoma cells. PC4 decreased cisplatin’s cytotoxic effects on lung adenocarcinoma in vivo and in vitro. Furthermore, PC4 positively correlated with SOX9 in multiple cancers. PC4 was an upstream regulator of SOX9 in lung adenocarcinoma. Furthermore, PC4 mediated lung adenocarcinoma cell sensitivity to the HIF-PH inhibitor DMOG and the mTOR inhibitor rapamycin, and PC4 mediated the synergistic effect of DMOG and cisplatin. Finally, PC4 destabilized HIF-1α upon cisplatin treatment. Our research showed that PC4 participates in mediating lung adenocarcinoma cell sensitivity to multiple drugs. Mechanistically, PC4 governs multiple downstream pathways associated with chemotherapy resistance, including the SOX9 and HIF-1α pathways. Thus, PC4 is a promising chemotherapeutic target in lung adenocarcinoma.

scholarly journals Lung adenocarcinoma cell-derived exosomal miR-328 promote osteoclastogenesis by targeting Nrp2

2021 ◽  
Author(s):  
Cheng Cheng Zhang ◽  
Jingru Qin ◽  
Lu Yang ◽  
Zhiyao Zhu ◽  
Xinle Qian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Bone Resorption ◽  
Lung Adenocarcinoma ◽  
Adenocarcinoma Cell ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Bone metastasis of lung cancer and detailed mechanisms are still elusive, and the roles of exosomes derived from lung adenocarcinoma cells in this process have attracted much attention. In this study, we found that lung adenocarcinoma cell-derived exosomes (LCC-Exos) promoted osteogenesis and bone resorption in vitro. Furthermore, LCC-Exos target bone in vivo and promoted bone resorption in vivo. Mechanistically, LCC-Exosomal miR-328 promoted bone resorption by targeting Nrp2 and LCC-ExosmiR-328 Inhibitors inhibited bone resorption in vivo. Thus, LCC-Exosomal miR-328 promote osteoclastogenesis by targeting Nrp2 and LCC-ExosmiR-328 Inhibitors may serve as a potential nanomedicine for the treatment of bone metastasis.

scholarly journals RETRACTED ARTICLE: Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma

2016 ◽  
Vol 7 (9) ◽  
pp. e2388-e2388 ◽  
Author(s):  
Shuang Wei ◽  
Zun-yi Zhang ◽  
Sheng-ling Fu ◽  
Jun-gang Xie ◽  
Xian-sheng Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitor ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Adenocarcinoma Cell ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Abstract Our previous study revealed that Ku80 was overexpressed in lung cancer tissues and hsa-miR-623 regulated the Ku80 expression; however, the detailed function of hsa-miR-623 in lung cancer was unclear. We identified that hsa-miR-623 bound to the 3'-UTR of Ku80 mRNA, thus significantly decreasing Ku80 expression in lung adenocarcinoma cells. Hsa-miR-623 was downregulated in lung adenocarcinoma tissues compared with corresponding non-tumorous tissues, and its expression was inversely correlated with Ku80 upregulation. Downregulation of hsa-miR-623 was associated with poor clinical outcomes of lung adenocarcinoma patients. Hsa-miR-623 suppressed lung adenocarcinoma cell proliferation, clonogenicity, migration and invasion in vitro. Hsa-miR-623 inhibited xenografts growth and metastasis of lung adenocarcinoma in vivo. Ku80 knockdown in lung adenocarcinoma cells suppressed tumor properties in vitro and in vivo similar to hsa-miR-623 overexpression. Further, hsa-miR-623 overexpression decreased matrix metalloproteinase-2 (MMP-2) and MMP-9 expression levels, with decreased ERK/JNK phosphorylation. Inhibition of hsa-miR-623 or overexpression of Ku80 promoted lung adenocarcinoma cell invasion, activated ERK/JNK phosphorylation and increased MMP-2/9 expressions, which could be reversed by ERK kinase inhibitor or JNK kinase inhibitor. In summary, our results showed that hsa-miR-623 was downregulated in lung adenocarcinoma and suppressed the invasion and metastasis targeting Ku80 through ERK/JNK inactivation mediated downregulation of MMP-2/9. These findings reveal that hsa-miR-623 may serve as an important therapeutic target in lung cancer therapy.

scholarly journals PD-L1 lncRNA splice promotes lung adenocarcinoma progression via enhancing c-Myc activity

2020 ◽  
Author(s):  
Shuang Qu ◽  
Zichen Jiao ◽  
Geng Lu ◽  
Bing Yao ◽  
Ting Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Great Promise ◽  
Non Coding Rna ◽  
Adenocarcinoma Cells ◽  
T Cell Immune Responses ◽  
Lung Adenocarcinoma Cells ◽  
Novel Strategy ◽  
L1 Protein

ABSTRACTAlthough blockade of programmed death-ligand 1 (PD-L1) to enhance T cell immune responses shows great promise in tumor immunotherapy, the efficacy of such immune-checkpoint inhibition strategy is limited for patients with solid tumors. The mechanism underlying the limited efficacy of PD-L1 inhibitors remains unclear. Here, we show that human lung adenocarcinoma, regardless of PD-L1 protein positive or negative, all produce a long non-coding RNA isoform of PD-L1 (PD-L1-lnc) via alternative splicing, which promotes lung adenocarcinoma proliferation and metastasis. PD-L1-lnc in various lung adenocarcinoma cells is significantly upregulated by IFNγ in a manner similar to PD-L1 mRNA. Both in vitro and in vivo studies demonstrate that PD-L1-lnc increases proliferation and invasion but decreases apoptosis of lung adenocarcinoma cells. Mechanistically, PD-L1-lnc directly binds to c-Myc and enhances c-Myc transcriptional activity downstream in lung adenocarcinoma cells. Our results provide targeting PD-L1-lnc−c-Myc axis as a novel strategy for lung cancer therapy.

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 GPR87 Promotes Metastasis through the AKT-eNOS-NO Axis in Lung Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 19
Author(s):  
Hye-Mi Ahn ◽  
Eun-Young Choi ◽  
Youn-Jae Kim
Keyword(s):  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
The Public ◽  
Adenocarcinoma Cells ◽  
No Signaling ◽  
Tcga Dataset ◽  
Patient Prognosis

Lung adenocarcinoma is one of the leading causes of cancer-related deaths. Despite the availability of advanced anticancer drugs for lung cancer treatment, the prognosis of patients still remains poor. There is a need to explore novel oncogenic mechanisms to overcome these therapeutic limitations. The functional experiments in vitro and in vivo were performed to evaluate the role of GPR87 expression on lung adenocarcinoma metastasis. The public lung adenocarcinoma TCGA dataset was used to determine the clinical relevance of GPR87 expression in patients with lung adenocarcinoma. GPR87 is upregulated in various cancer; however, the biological function of GPR87 has not yet been established in lung adenocarcinoma. In this study, we found that GPR87 expression is upregulated in lung adenocarcinoma and is associated with poor patient prognosis. Additionally, we showed that GPR87 overexpression promotes invasiveness and metastasis of lung adenocarcinoma cells. Furthermore, we demonstrated that AKT-eNOS-NO signaling is a novel downstream pathway of GPR87 in lung adenocarcinoma. Conversely, we confirmed that silencing of GPR87 expression suppressed these phenotypes. Our results reveal the oncogenic function of GPR87 in cancer progression and metastasis through the activation of eNOS as a key mediator. Therefore, we propose that targeting eNOS could be a novel therapeutic strategy to improve the clinical treatment of lung adenocarcinoma.

scholarly journals Anti-Tumor Effects of Biomimetic Sulfated Glycosaminoglycans on Lung Adenocarcinoma Cells in 2D and 3D In Vitro Models

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2595
Author(s):  
Nada Al Matari ◽  
George Deeb ◽  
Hiba Mshiek ◽  
Ansam Sinjab ◽  
Humam Kadara ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
In Vitro Models ◽  
Trypan Blue Exclusion ◽  
Cell Functions ◽  
Adenocarcinoma Cells ◽  
Diphenyltetrazolium Bromide ◽  
And Migration ◽  
Sphere Formation

Lung cancer development relies on cell proliferation and migration, which in turn requires interaction with extracellular matrix (ECM) components such as glycosaminoglycans (GAGs). The mechanisms through which GAGs regulate cancer cell functions are not fully understood but they are, in part, mediated by controlled interactions with cytokines and growth factors (GFs). In order to mechanistically understand the effect of the degree of sulfation (DS) of GAGs on lung adenocarcinoma (LUAD) cells, we synthesized sulfated alginate (AlgSulf) as sulfated GAG mimics with DS = 0.0, 0.8, 2.0, and 2.7. Human (H1792) and mouse (MDA-F471) LUAD cell lines were treated with AlgSulf of various DSs at two concentrations 10 and 100 µg/mL and their anti-tumor properties were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), trypan blue exclusion, and wound healing assays for 2D models and sphere formation assay for the 3D model. The proliferation and number of live MDA-F471 cells at the concentration of 100 µg/mL decreased significantly with the increase in the DS of biomimetic GAGs. In addition, the increase in the DS of biomimetic GAGs decreased cell migration (p < 0.001 for DS = 2.0 and 2.7 compared to control) and decreased the diameter and number of spheres formed (p < 0.001). The increased DS of biomimetic GAGs attenuated the expression of cancer stem cell (CSC)/progenitor markers in the 3D cultures. In conclusion, GAG-mimetic AlgSulf with increased DS exhibit enhanced anti-proliferative and migratory properties while also reducing growth of KRAS-mutant LUAD spheres in vitro. We suggest that these anti-tumor effects by GAG-mimetic AlgSulf are possibly due to differential binding to GFs and consequential decreased cell stemness. AlgSulf may be suitable for applications in cancer therapy after further in vivo validation.

DOdFMG, a genistein derivative, as effective anti lung adenocarcinoma cell agents in vitro and in vivo

2008 ◽  
Vol 32 (3) ◽  
pp. S28-S29
Author(s):  
Bo Peng ◽  
Cao Jian Guo ◽  
Cheng Kun Wang ◽  
Sha Sha Fan ◽  
Zhi Min He
Keyword(s):  
Lung Adenocarcinoma ◽  
Adenocarcinoma Cell

scholarly journals C/EBPα Suppresses Lung Adenocarcinoma Cell Invasion and Migration by Inhibiting β-Catenin

2017 ◽  
Vol 42 (5) ◽  
pp. 1779-1788 ◽  
Author(s):  
Jinchang Lu ◽  
Chunling Du ◽  
Junxia Yao ◽  
Bo Wu ◽  
Yanhong Duan ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Lung Adenocarcinoma ◽  
Cell Invasion ◽  
Migration And Invasion ◽  
Adenocarcinoma Cell ◽  
Invasion And Migration ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
And Migration

Background/Aims: The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) is a basic leucine zipper transcription factor that plays essential roles in tumor progression. Although decreased or absent C/EBPα expression in many cancers suggests a possible role for C/EBPα as a tumor suppressor, the functions of C/EBPα in lung adenocarcinoma remain unclear. Methods: Here, C/EBPα expression levels in 26 lung adenocarcinoma and para-carcinoma tissue samples were detected by qRT-PCR and immunohistochemistry. Cell transwell assays, wound healing assay and three-dimensional spheroid invasion assay were performed to assess the effects of C/EBPα on migration and invasion in lung adenocarcinoma cells in vitro. Western blotting was applied to analyze the potential mechanisms. Results: C/EBPα was found to be decreased in lung adenocarcinoma tissues compared to para-carcinoma tissues. Overexpression of C/EBPα significantly inhibited the migration and invasion of lung adenocarcinoma cells. In addition, C/EBPα overexpression suppressed the epithelial–mesenchymal transition (EMT) that was characterized by a gain of epithelial and loss of mesenchymal markers. Further study showed that C/EBPα suppressed the transcription of β-catenin and downregulated the levels of its downstream targets. Conclusion: Our data suggest that C/EBPα inhibits lung adenocarcinoma cell invasion and migration by suppressing β-catenin-mediated EMT in vitro. Thus, C/EBPα may be helpful as a potential target for treatment of lung adenocarcinoma.

Gracilaria edulis exhibit antiproliferative activity against human lung adenocarcinoma cell line A549 without causing adverse toxic effect in vitro and in vivo

2016 ◽  
Vol 7 (2) ◽  
pp. 1155-1165 ◽  
Author(s):  
Ravi Sakthivel ◽  
Samuthirapandi Muniasamy ◽  
Govindaraju Archunan ◽  
Kasi Pandima Devi
Keyword(s):  
Lung Adenocarcinoma ◽  
Antiproliferative Activity ◽  
Human Lung ◽  
Adenocarcinoma Cell Line ◽  
Gracilaria Edulis ◽  
Adenocarcinoma Cell ◽  
Lung Adenocarcinoma Cell Line ◽  
Human Lung Adenocarcinoma Cell

In the present study, the antiproliferative potential of various solvent extracts ofGracilaria edulis(GE) was tested against various cancer cell lines.

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