scholarly journals P2‐33: Blocking MMP‐12‐modulated epithelial‐mesenchymal transition by repurposing penfluridol retsrains lung adenocarcinoma metastasis via UPA/UPAR/TGF‐Β/AKT pathway

Respirology ◽  
2021 ◽  
Vol 26 (S3) ◽  
pp. 126-126
Keyword(s):  
Lung Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Akt Pathway ◽  
Mesenchymal Transition

scholarly journals CNTN-1 Enhances Chemoresistance in Human Lung Adenocarcinoma Through Induction of Epithelial-Mesenchymal Transition by Targeting the PI3K/Akt Pathway

2017 ◽  
Vol 43 (2) ◽  
pp. 465-480 ◽  
Author(s):  
Ruijie Zhang ◽  
Shenghua Sun ◽  
Fuyun Ji ◽  
Chun Liu ◽  
Hua Lin ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cisplatin Resistance ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Malignant Progression ◽  
Akt Pathway ◽  
Vimentin Expression ◽  
Mesenchymal Transition

Background/Aims: Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1) is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. Methods: EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin) expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression) by using real-time time PCR and Western blotting. Other methods, including CNTN-1 overexpression in A549 cells and CNTN-1 knockdown in A549/DDP cells, were also used to investigate the role of CNTN-1 in mediating the EMT phenotype and thr resulting cisplatin resistance and malignant progression of cancer cells in vitro and in vivo. Results: A549/DDP cells exhibited an EMT phenotype and aggravated malignant behaviors. CNTN-1 knockdown in A549/DDP cells partly reversed the EMT phenotype, increased drug sensitivity, and attenuated the malignant progression whereas CNTN-1 overexpression in A549 cells resulted in the opposite trend. Furthermore, the PI3K/Akt pathway was involved in the effects of CNTN-1 on EMT progression in A549/DDP cells, verified by the xenograft mouse model. Conclusion: CNTN-1 promotes cisplatin resistance in human cisplatin-resistant lung adenocarcinoma through inducing the EMT process by activating the PI3K/Akt signaling pathway. CNTN-1 may be a potential therapeutic target to reverse chemoresistance in cisplatin-resistant lung adenocarcinoma.

scholarly journals Upregulation of LINC01426 promotes the progression and stemness in lung adenocarcinoma by enhancing the level of SHH protein to activate the hedgehog pathway

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Xiaoli Liu ◽  
Zuwei Yin ◽  
Linping Xu ◽  
Huaimin Liu ◽  
Lifeng Jiang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Bioinformatics Analysis ◽  
Epithelial Mesenchymal Transition ◽  
Mrna Level ◽  
Hedgehog Pathway ◽  
Biological Processes ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Functional Roles ◽  
Rip Assay

AbstractLong noncoding RNAs (lncRNAs) play crucial roles in regulating a variety of biological processes in lung adenocarcinoma (LUAD). In our study, we mainly explored the functional roles of a novel lncRNA long intergenic non-protein coding RNA 1426 (LINC01426) in LUAD. We applied bioinformatics analysis to find the expression of LINC01426 was upregulated in LUAD tissue. Functionally, silencing of LINC01426 obviously suppressed the proliferation, migration, epithelial–mesenchymal transition (EMT), and stemness of LUAD cells. Then, we observed that LINC01426 functioned through the hedgehog pathway in LUAD. The effect of LINC01426 knockdown could be fully reversed by adding hedgehog pathway activator SAG. In addition, we proved that LINC01426 could not affect SHH transcription and its mRNA level. Pull-down sliver staining and RIP assay revealed that LINC01426 could interact with USP22. Ubiquitination assays manifested that LINC01426 and USP22 modulated SHH ubiquitination levels. Rescue assays verified that SHH overexpression rescued the cell growth, migration, and stemness suppressed by LINC01426 silencing. In conclusion, LINC01426 promotes LUAD progression by recruiting USP22 to stabilize SHH protein and thus activate the hedgehog pathway.

scholarly journals CircRNA PIP5K1A promotes the progression of glioma through upregulation of TCF12/PI3K/AKT pathway by sponging miR-515-5p

2020 ◽  
Author(s):  
Kebin Zheng ◽  
Haipeng Xie ◽  
Xiaosong Wu ◽  
Xichao Wen ◽  
Zhaomu Zeng ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Cell Model ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Circular Rnas ◽  
Rt Pcr ◽  
Mesenchymal Transition ◽  
Normal Tissues

Abstract BackgroundIncreasing studies have revealed that circular RNAs (CircRNAs) make great contribution to regulating tumor progression. Therefore, we intended to explore the expression characteristics, function, and related mechanisms of a novel type of circRNA, PIP5K1A in glioma. MethodsFirstly, RT-PCR was carried out to examine CircPIP5K1A expression in glioma tissues and adjacent normal tissues, and the correlation between CircPIP5K1A level and the clinical pathological indicators of glioma was analyzed. Then, the CircPIP5K1A expression in various glioma cell lines was detected, and a cell model of CircPIP5K1A overexpression and knockdown was constructed. Subsequently, cell proliferation and viability were detected by CCK8 method and BrdU staining, apoptosis was detected by flow cytometry, and cell invasion was examined by Transwell assay. The expression of TCF12, PI3K/AKT pathway apoptotic related proteins (including Caspase3, Bax and Bcl2) and epithelial-mesenchymal transition (EMT) markers (including E-cadherin, Vimentin and N-cadherin) by western blot or RT-PCR. ResultsThe results manifested that CircPIP5K1A was obviously upregulated in glioma tissues (compared with that in normal adjacent tissues), and overexpressed CircPIP5K1A was distinctly related to glioma volume and histopathological grade. Functionally, overexpressing CircPIP5K1A notably elevated the proliferation, invasion, EMT of glioma cells, and inhibited apoptosis both in vivo and in vitro. Besides, CircPIP5K1A also upregulated TCF12 and PI3K/AKT pathway activation. Bioinformatics analysis testified that miR-515-5p was a common target of CircPIP5K1A and TCF12, while dual luciferase reporter assay and RNA immunocoprecipitation (RIP) experiment further confirmed that CircPIP5K1A targeted miR-515-5p, which bound the 3'-untranslated region (UTR) of TCF12. ConclusionsAltogether, the study illustrated that CircPIP5K1A is a potential prognostic marker in glioma and regulates the development of glioma through the modulating miR-515-5p mediated TCF12/PI3K/AKT axis.

scholarly journals lncCRLA enhanced chemoresistance in lung adenocarcinoma that underwent epithelial-mesenchymal transition

2021 ◽  
Author(s):  
Weili Min ◽  
Liangzhang Sun ◽  
Burong Li ◽  
Xiao Gao ◽  
Shuqun Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Metastatic Potential ◽  
Caspase 8 ◽  
Mesenchymal Transition ◽  
Adenocarcinoma Cells ◽  
Signaling Axis ◽  
Lung Adenocarcinoma Cells ◽  
Paclitaxel Liposome

EMT confers increased metastatic potential and the resistance to chemotherapies to cancer cells. However, the precise mechanisms of EMT-related chemotherapy resistance remain unclear. c-Src-mediated Caspase-8 phosphorylation essential for EMT in lung adenocarcinoma cell lines preferentially occurs in cells with the mesenchymal phenotype, resulting in chemoresistance to cisplatin plus paclitaxel inpatients with resectable lung adenocarcinoma and a significantly worse 5-year PFS. Cisplatin killed lung adenocarcinoma cells regardless of Caspase-8. Paclitaxel-triggered necroptosis in lung adenocarcinoma cells was dependent on the phosphorylation or deficiency of Caspase-8, during which FADD interacted with RIPK1 to activateRIPK1/RIPK3/MLKL signaling axis. Accompanied with c-Src-mediated Caspase-8 phosphorylation to trigger EMT, a novel lncRNA named lncCRLA was markedly upregulated and inhibited RIPK1-induced necroptosis by impairing RIPK1-RIPK3 interaction via binding to the intermediate domain of RIPK1. Dasatinib mitigated c-Src-mediated phosphorylation of Caspase-8-induced EMT and enhanced necroptosis in mesenchymal-like lung adenocarcinoma cells treated with paclitaxel, while c-FLIP knockdown predominantly sensitized the mesenchymal-like lung adenocarcinoma cells to paclitaxel+dasatinib. c-Src-Caspase-8 interaction initiates EMT and chemoresistance viaCaspase-8 phosphorylation and lncCRLA expression, to which the dasatinib/paclitaxel liposome+siFLIP regimen was lethal.

scholarly journals MicroRNA-32-5p inhibits epithelial-mesenchymal transition and metastasis in lung adenocarcinoma by targeting SMAD family 3

2021 ◽  
Vol 12 (8) ◽  
pp. 2258-2267
Author(s):  
Jin-Xing Zhang ◽  
Wei Yang ◽  
Jun-Zheng Wu ◽  
Chun Zhou ◽  
Sheng Liu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

Radiological features of resected lung adenocarcinoma with epithelial–mesenchymal transition

2020 ◽  
Author(s):  
Taichi Matsubara ◽  
Tetsuzo Tagawa ◽  
Gouji Toyokawa ◽  
Takeshi Kamitani ◽  
Kazuki Takada ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Radiological Features
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