HOXA4-Dependent Transcriptional Activation of AXL Promotes Cisplatin- Resistance in Lung Adenocarcinoma Cells

2019 ◽  
Vol 18 (14) ◽  
pp. 2062-2067 ◽  
Author(s):  
Shuo Yu ◽  
Hui Ren ◽  
Yang Li ◽  
Xuan Liang ◽  
Qian Ning ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Transcriptional Regulation ◽  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Cisplatin Resistance ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Encoding Gene

Background: Lung cancer is one of the most leading causes of cancer-related deaths in adults worldwide. Non-Small Cell Lung Cancer (NSCLC), which comprises 80 to 85% of all lung cancers, is the most lethal subtype of lung cancer with a 5-year survival of less than 13%. In this study, we identified a poorly-studied kinase PDK4 as the most up-regulated kinase encoding gene in Cisplatin resistant lung adenocarcinoma. Methods: In vitro cell viability assay and in vivo tumor xenograft assay were used in the detection of cell proliferation. RNA isolation, quantitative Real-Time PCR, Western blot analysis, immunohistochemistry were used to investigate the expression of RNA and protein. Lentivirus infection was used to regulate gene expression. Luciferase assays were used to monitor EPAS1 promoter activity. Results: In vivo PDK4 expression was elevated in a Cisplatin-resistant population of lung adenocarcinoma cells, PDK4-dependent Cisplatin-resistance promotes tumor growth of lung adenocarcinoma in vivo and in vitro, clinically PDK4 expression was associated with poor prognosis in lung adenocarcinoma patients, mechanically PDK4 promoted cell growth and Cisplatin-resistance of lung adenocarcinoma via transcriptional regulation of endothelial PAS domain-containing protein 1 (EPAS1). Conclusion: PDK4 is the most up-regulated kinase encoding gene in Cisplatin resistant lung adenocarcinoma and PDK4-dependent Cisplatin-resistance promotes tumor growth of lung adenocarcinoma mainly through transcriptional regulation of EPAS1. Enriched PDK4 expression was correlated with the poor prognosis of lung cancer patients, indicating that PDK4 could be a potential therapeutic target for Cisplatin-resistant 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.

STK33-dependent transcriptional regulation of SFTA3 induces Cisplatin-resistance in lung adenocarcinoma

2019 ◽  
Vol 19 ◽  
Author(s):  
Kuilong Zhou ◽  
Runzhi Dong ◽  
Zhiheng Wang ◽  
Zhian Tang ◽  
Xuezhen Gao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Transcriptional Regulation ◽  
Lung Adenocarcinoma ◽  
Cisplatin Resistance ◽  
Serine Threonine Kinase ◽  
Lung Cancer Patients ◽  
Threonine Kinase ◽  
Signaling Axis

: Drug-resistance has become a major obstacle for Cisplatin usage in non-small cell lung cancer. In this study, we identified a poorly-studied kinase Serine/Threonine Kinase 33 (STK33) as the most up-regulated kinase encoding gene in Cisplatin resistant lung adenocarcinoma. Additionally, STK33-dependent Cisplatin-resistance promotes tumor growth of lung adenocarcinoma both in vitro and in vivo. Clinically, STK33 expression was enriched in lung adenocarcinoma and was correlated to poor prognosis of lung cancer patients. Mechanically, STK33 promoted cell growth and Cisplatin-resistance of lung adenocarcinoma via transcriptional regulation of surfactant associated 3 (SFTA3), indicating that STK33-SFTA3 signaling axis could be a potential therapeutic target for Cisplatin-resistant lung adenocarcinoma.

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 Hsa_circ_0020850 promotes the malignant behaviors of lung adenocarcinoma by regulating miR-326/BECN1 axis

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaoju Li ◽  
Shengtian Su ◽  
Dan Ye ◽  
Zhigao Yu ◽  
Wenjing Lu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Mice Model ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Abstract Background Circular RNAs (circRNAs) are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma. However, the function and underlying mechanism of circ_0020850 in lung adenocarcinoma remain unknown. Methods The levels of circ_0020850, microRNA-326 (miR-326), and Beclin1 (BECN1) were analyzed by real-time quantitative polymerase chain reaction and western blot analyses. The migration and invasion were determined by wound healing and transwell assays, respectively. Colony formation assay was used to assess cell proliferation ability. The angiogenic ability was analyzed by Matrigel angiogenesis assay. The apoptosis rate was calculated by flow cytometry assay. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were conducted to confirm the interaction relationship among circ_0020850, miR-326, and BECN1. A xenograft mice model was established to assess the role of circ_0020850 in vivo. Results We found that circ_0020850 was obviously overexpressed in lung adenocarcinoma tissues and cells. Knockdown of circ_0020850 inhibited migration, invasion, proliferation, and angiogenesis but induced apoptosis in lung adenocarcinoma cells in vitro, as well as curbed tumor growth in vivo. MiR-326 was a target of circ_0020850, and knockdown of miR-326 abolished the suppression effect of circ_0020850 on the malignant behaviors of lung adenocarcinoma cells. Additionally, miR-326 could negatively regulate BECN1 expression, thereby regulating lung adenocarcinoma cell phenotypes. Importantly, circ_0020850 could directly bind to miR-326 and thus relieve miR-326-mediated inhibition on BECN1. Conclusion Circ_0020850 promoted the malignant development of lung adenocarcinoma by regulating miR-326/BECN1 axis, indicating that circ_0020850 might serve as a promising target for the diagnosis and treatment of lung adenocarcinoma patients.

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