miR‑197‑3p‑induced downregulation of lysine 63 deubiquitinase promotes cell proliferation and inhibits cell apoptosis in lung adenocarcinoma cell lines

e22051 Background: Treatment of non-small cell lung cancer remains a clinical challenge despite the migration from cytotoxic chemotherapies to targeted agents. Myosin light chain kinase (MLCK) is a protein involved in phosphorylation of regulatory chains of myosin, thereby regulating the contraction of myosin II. The 210 KDa non-muscle MLCK isoform (nmMLCK), expressed in endothelial cells, regulates cell shape and motility, and increases EGFR-mediated proliferation of hepatocytes. Furthermore, inhibitors of MLCK such as ML-7 and ML-9 have been shown to decrease invasiveness of pancreatic prostate cancer cell lines. Clinically, levels of MLCK gene (MYLK) mRNA correlate with increased risk of disease recurrence and development of distant metastasis in lung cancer. These data suggest a potential role for MLCK in lung cancer tumorigenesis and metastasis. Methods: H-23 and H-441 human lung adenocarcinoma cell lines were treated for 12hrs with MLCK chemical inhibitor, ML-7 (20uM), and harvested at 24hr, 48hr, and 72hr for MTS Assay. Cell proliferation was assessed with MTS Assay per manufacturer protocol (Promega). H-23 cells were transiently transfected with a FLAG-tagged (WT) nmMLCK overexpression vector using Fugene Transfection Kit per manufacturer protocol (Promega). Results: While no significant difference in proliferation was noted in A-549 cells, both H-23 and H-441 cells showed a decrease in cell proliferation with inhibition of MLCK. H-23 cells also showed an increase in proliferation when transiently transfected with an MLCK-overexpression vector. Conclusions: Inhibition of endogenous nmMLCK decreases H-23 and H-441 proliferation. Conversely, an increase in nmMLCK expression in vitro increases cell proliferation in H23 cells. These results suggest that MLCK/MYLK may participate in regulation of lung adenocarcinoma cell proliferation.

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Faculty Opinions recommendation of MiR-374a suppresses lung adenocarcinoma cell proliferation and invasion by targeting TGFA gene expression.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726373646.793522732 ◽

2016 ◽

Author(s):

Robert Coffey ◽

Bhuminder Singh

Keyword(s):

Gene Expression ◽

Cell Proliferation ◽

Lung Adenocarcinoma ◽

Adenocarcinoma Cell ◽

Proliferation And Invasion

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LncRNA SGMS1‐AS1 regulates lung adenocarcinoma cell proliferation, migration, invasion, and EMT progression via miR‐106a‐5p/MYLI9 axis

Thoracic Cancer ◽

10.1111/1759-7714.14043 ◽

2021 ◽

Author(s):

Ting Liu ◽

Chunli Yang ◽

Weizhen Wang ◽

Chunmei Liu

Keyword(s):

Cell Proliferation ◽

Lung Adenocarcinoma ◽

Adenocarcinoma Cell

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PLAUR Confers Resistance to Gefitinib Through EGFR/P-AKT/Survivin Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000491071 ◽

2018 ◽

Vol 47 (5) ◽

pp. 1909-1924 ◽

Cited By ~ 8

Author(s):

Jian Zhou ◽

Kwang Joo Kwak ◽

Zuoren Wu ◽

Dawei Yang ◽

Jing Li ◽

...

Keyword(s):

Cell Proliferation ◽

Membrane Potential ◽

Tyrosine Kinase ◽

Lung Adenocarcinoma ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Mitochondrial Membrane ◽

Human Lung ◽

Nsclc Patients ◽

Gefitinib Resistance

Background/Aims: Tyrosine kinase inhibitor gefitinib significantly improves the survival of patients with non-small-cell lung cancer (NSCLC) by inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase. However, patients eventually develop resistance to gefitinib through uncharacterized mechanisms. It is known that plasminogen activator urokinase receptor (PLAUR) plays an important role in cell proliferation, migration and apoptosis. However, the role of PLAUR, particularly exosomal PLAUR in gefitinib resistance in NSCLC has not been reported. The aim of this study is to determine the relationship between PLAUR and gefitinib resistance. Methods: In this study, a tethered cationic lipoplex nanoparticle (TCLN) biochip containing molecular beacons was used as probes to detect PLAUR mRNA in plasma exosomes from patients with gefitinib-sensitive and -resistant NSCLC. In vitro, Real-time PCR was used to examine the expression of PLAUR mRNA and Western blot was applied to examine the expression of related proteins. The gene knockdown was achieved by Lentivirus based RNA silence technique. The cell counting kit-8 assay and EdU incorporation were used to examine cell proliferation. The flow cytometry was applied to determine cell apoptosis and cell cycle, while the mitochondrial membrane potential was measured by JC-1 dye assay. Signaling pathway affected by PLAUR knockdown was identified by cDNA Microarray. The effect of PLAUR knockdown on tumorigenesis was analyzed in vivo. Results: We found that the exosomal PLAUR mRNA in the plasma of gefitinib-resistant NSCLC patients was significantly increased compared to that of gefitinib-sensitive NSCLC patients. The PLAUR mRNA and soluble PLAUR protein were also significantly increased in gefitinib-resistant human lung adenocarcinoma PC9R cells compared to gefitinib-sensitive PC9 cells. Silencing PLAUR in PC9R cells impaired mitochondrial membrane potential and increased cell apoptosis via EGFR/p-AKT/survivin signaling pathway. Furthermore, EGFR was upregulated in the geftinib-resistant PC9R cells, and knockdown of EGFR significantly increased cell apoptosis. Conclusions: Taken together, our results demonstrated that PLAUR induces geftinib-resistance through EGFR/p-AKT/survivin signaling pathway in gefitinib-resistant human lung adenocarcinoma cells. PLAUR could be a novel therapeutic target for gefitinib-resistant NSCLC patients.

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Characterization of the Mucin Differentiation in Human Lung Adenocarcinoma Cell Lines

American Journal of Respiratory Cell and Molecular Biology ◽

10.1165/ajrcmb/7.2.161 ◽

1992 ◽

Vol 7 (2) ◽

pp. 161-171 ◽

Cited By ~ 36

Author(s):

Pan-Chyr Yang ◽

Kwen-Tay Luh ◽

Reen Wu ◽

Cheng-Wen Wu

Keyword(s):

Lung Adenocarcinoma ◽

Cell Lines ◽

Human Lung ◽

Adenocarcinoma Cell ◽

Human Lung Adenocarcinoma ◽

Human Lung Adenocarcinoma Cell

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Human lung adenocarcinoma cell lines with different lung colonization potential (LCP), and a correlation between expression of sialosyl dimeric Lex (defined by MAb FH6) and LCP

Clinical & Experimental Metastasis ◽

10.1007/bf01753728 ◽

1991 ◽

Vol 9 (3) ◽

pp. 245-257 ◽

Cited By ~ 30

Author(s):

H. Inufusa ◽

N. Kojima ◽

M. Yasutomi ◽

S. Hakomori

Keyword(s):

Lung Adenocarcinoma ◽

Cell Lines ◽

Human Lung ◽

Adenocarcinoma Cell ◽

Human Lung Adenocarcinoma ◽

Lung Colonization ◽

Colonization Potential ◽

Human Lung Adenocarcinoma Cell

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MicroRNA-3666 inhibits lung cancer cell proliferation, migration, and invasiveness by targeting BPTF

Biochemistry and Cell Biology ◽

10.1139/bcb-2018-0301 ◽

2019 ◽

Vol 97 (4) ◽

pp. 415-422 ◽

Cited By ~ 3

Author(s):

Linqing Pan ◽

Zhipeng Tang ◽

Lina Pan ◽

Ranran Tang

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Lung Adenocarcinoma ◽

Signaling Pathways ◽

Histological Grade ◽

Clinical Stage ◽

Luciferase Reporter ◽

Advanced Clinical Stage ◽

Mesenchymal Transition ◽

Adenocarcinoma Cell

A previous study by our group indicted that overexpression of bromodomain PHD-finger transcription factor (BPTF) occurs in lung adenocarcinoma, and is closely associated with advanced clinical stage, higher numbers of metastatic lymph nodes, the occurrence of distant metastasis, low histological grade, and poor prognosis. Down-regulation of BPTF inhibited lung adenocarcinoma cell proliferation and promoted lung adenocarcinoma cell apoptosis. The purpose of this study is to identify valuable microRNAs (miRNAs) that target BPTF to modulate lung adenocarcinoma cell proliferation. In our results, we found that miR-3666 was notably reduced in lung adenocarcinoma tissues and cell lines. Using an miR-3666 mimic, we discovered that cell proliferation, migration, and invasiveness were suppressed by miR-3666 overexpression, but these were all enhanced when the expression of miR-3666 was reduced. Moreover, bioinformatics analysis using the TargetScan database and miRanda software suggested a putative target site in BPTF 3′-UTR. Furthermore, using a luciferase reporter assay, we verified that miR-3666 directly targets the 3′-UTR of BPTF. Using Western blot we discovered that overexpression of miR-3666 negatively regulates the protein expression of BPTF. Finally, we identified that the PI3K–AKT and epilthelial–mesenchymal transition (EMT) signaling pathways were inhibited by miR-3666 overexpression in lung cancer cells. In conclusion, our data indicate that miR-3666 could play an essential role in cell proliferation, migration, and invasiveness by targeting BPTF and partly inhibiting the PI3K–AKT and EMT signaling pathways in human lung cancers.

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