scholarly journals miR-449a Suppresses LDHA-Mediated Glycolysis to Enhance the Sensitivity of Non-Small Cell Lung Cancer Cells to Ionizing Radiation

2018 ◽  
Vol 26 (4) ◽  
pp. 547-556 ◽  
Author(s):  
Liang Li ◽  
Huijuan Liu ◽  
Lianjiang Du ◽  
Pan Xi ◽  
Qian Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Ionizing Radiation ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
A549 Cells ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung

MicroRNA dysregulation contributes to malignant progression, dissemination, and profound treatment resistance in multiple cancers. miR-449a is recognized as a tumor suppresser. However, the roles of miR-449a in lung cancer initiation and progression are largely unknown. Our study aims to investigate the roles and underlying mechanism of miR-449a in modulating sensitivity to ionizing radiation (IR) in non-small cell lung cancer (NSCLC). Lung cancer cells were transfected with miR-449a mimics or negative control and exposed to IR; the levels of target protein, glycolysis, cell viability, apoptosis, and DNA damage were examined. miR-449a was suppressed in lung cancer tissues and cancer cells (A549 and H1299). IR exposure significantly increased the expression of miR-449a in A549 cells at doses ranging from 4 to 8 Gy at 24 h, whereas no significant change in miR-449a was found in H1299 cells after IR. When A549 cells were exposed to IR at a dose of 8 Gy, the miR-449a level only had an acute increase within 12 h. miR-449a restoration dramatically suppressed IR-induced cell apoptosis and DNA damage in both A549 and H1299 cells. Bioinformatics analysis indicated that lactate dehydrogenase A (LDHA) was a potential target of miR-449a. miR-449a mimic transfection substantially suppressed the LDHA expression and production of lactate catalyzed by LDHA as well as glucose uptake. We confirmed that miR-449a could bind to the 3′-UTR of LDHA mRNA using luciferase reporter assay. LDHA siRNA-transfected cells showed enhanced cell apoptosis and DNA damage in response to IR exposure. miR-449a upregulation enhanced IR sensitivity of lung cancer cells by suppressing LDHA and the subsequent glycolysis.

Nrf2/ARE pathway activation is involved in negatively regulating heat-induced apoptosis in non-small cell lung cancer cells

2020 ◽  
Vol 52 (4) ◽  
pp. 439-445
Author(s):  
Wenyue Xie ◽  
Benxu Tan ◽  
Zhenzhou Yang ◽  
Xian Yu ◽  
Lingxiu Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Heat Stress ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung ◽  
Nrf2 Activation

Abstract Hyperthermia, particularly in combination with chemoradiotherapy, is widely used to treat various cancers. However, hyperthermia treatment is often insufficient due to thermo-tolerance. To date, the detailed mechanism underlying thermo-tolerance has not been clarified. The nuclear factor erythroid 2-related factor 2 (Nrf2)/ antioxidant response element (ARE) pathway is an important cellular cytoprotective defense system that is activated by various stresses. In this study, using immunocytochemistry and western blot analysis, we demonstrated that heat stress induced Nrf2/ARE activation through the nuclear translocation of Nrf2 in non-small cell lung cancer cells. Luciferase activity was also increased. Additionally, antioxidant enzymes were increased through Nrf2 activation after heat stress. Transfection of lung cancer cells with siRNA directed against Nrf2 increased heat cytotoxicity and cell apoptosis. Heat stress could induce reactive oxygen species (ROS) accumulation, while the antioxidant NAC obviously reduced cell apoptosis ratio, indicating that heat stress induced cell apoptosis in a ROS-dependent manner. Knockdown of Nrf2 led to an abnormal elevation of ROS, and the antioxidant NAC could increase Nrf2 activation, indicating that ROS and Nrf2 act within a negative feedback loop. Taken together, these results demonstrated that Nrf2 pathway is important for maintaining resistance to heat stress, and we postulated that Nrf2 may represent a potential therapeutic target for hyperthermia in lung cancer.

scholarly journals miR-149 Inhibits Non-Small-Cell Lung Cancer Cells EMT by Targeting FOXM1

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yang Ke ◽  
Weiyong Zhao ◽  
Jie Xiong ◽  
Rubo Cao
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung ◽  
Mesenchymal Transition

MicroRNAs (miRNAs) have been implied to play crucial roles for epithelial-to-mesenchymal transition (EMT) of non-small-cell lung cancer cells (NSCLC cells). Here we found that the expression of miR-149, downregulated in lung cancer, was inversely correlated with invasive capability and the EMT phenotype of NSCLC cells. miR-149 inhibited EMT in NSCLC cells. Furthermore, we demonstrated that miR-149 directly targeted Forkhead box M1 (FOXM1), and FOXM1 was involved in the EMT induced by TGF-β1 in A549 cells. Overexpression of FOXM1 restored EMT process inhibited by miR-149. Our work suggested that miR-149 might be an EMT suppressor in NSCLC cells.

scholarly journals Iodide sensitizes genetically modified non-small cell lung cancer cells to ionizing radiation

2005 ◽  
Vol 13 (1) ◽  
pp. 74-81 ◽  
Author(s):  
L Zhang ◽  
S Sharma ◽  
J M Hershman ◽  
G A Brent ◽  
S M Dubinett ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Ionizing Radiation ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Genetically Modified ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung

Overexpression of Calcium Activated Chloride Channel A4 Suppressed the Proliferation, Invasion and Gemcitabine Resistance of Non-Small Cell Lung Cancer Cells

2020 ◽  
Vol 10 (4) ◽  
pp. 435-442
Author(s):  
Ruowen Zhang ◽  
Aihua Ren ◽  
Zhaohui Wang ◽  
Dawei Wang
Keyword(s):  
Lung Cancer ◽  
Wound Healing ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Small Cell Lung

Lung cancer is one kind of the malignant tumor with high mortality. And non-small cell lung cancer is the main subtype of lung cancer. And the proteins of CLCA family (CLCA1, CLCA2 and CLCA4) played an inhibitory role in the occurrence and development of multiple types of tumors. However, the effect of CLCA4 on non-small cell lung cancer cells remains unclear. In our study, we used the lentivirus to establish the overexpressed CLCA4 A549 cells. Next, the CCK-8 and clone formation assays were performed to detect the changes of proliferation of A549 cells. The wound healing and transwell assays were performed to determine the changing of the migration and invasion of A549 cells. Then gemcitabine was used to treat these cells and the CCK-8, wound healing and transwell assays were carried out to detect the effect of the combination of gemcitabine and the overexpression of CLCA4 on the proliferation, migration and invasion of A549 cells. After the overexpression of CLCA4, the clone formation and mobility of A549 cells was enhanced. Furthermore, the overexpression of CLCA4 induced the apoptosis of A549 cells and promoted the expression of apoptosis related proteins. The combination of gemcitabine and the overexpression of CLCA4 further suppressed the proliferation, migration and invasion of A549 cells. CLCA4 inhibited the proliferation, migration and invasion of non-small cell lung cancer cells. CLCA4 also strengthened the sensitivity of non-small cell lung cancer cells for gemcitabine.

scholarly journals MiR-222-3p Promotes Cell Proliferation and Inhibits Apoptosis by Targeting PUMA (BBC3) in Non-Small Cell Lung Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382092255
Author(s):  
Weijun Chen ◽  
Xiaobo Li
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung ◽  
Binding Component

MicroRNAs have been demonstrated to be critical regulators in tumor progression, including non-small cell lung cancer. MicroRNA-222-3p has been reported to function as a tumor suppressor or oncogene in several types of cancer, but its function role in non-small cell lung cancer has not been uncovered. In this study, we first found the expression of microRNA-222-3p was significantly increased in non-small cell lung cancer tissues and cell lines. MicroRNA-222-3p inhibitor decreased the activity of non-small cell lung cancer cells to proliferate and increased cell apoptosis using cell counting kit-8, flow cytometry, and caspase-3 activity analysis. Overexpressed microRNA-222-3p in non-small cell lung cancer cells promoted cell proliferation, but decreased cell apoptosis. Moreover, Bcl-2-binding component 3 was the target gene of microRNA-222-3p, and its knockdown weakened the regulatory effect of microRNA-222-3p inhibitor on cell proliferation and apoptosis in non-small cell lung cancer cells. In conclusion, microRNA-222-3p plays a significant role in the regulation of Bcl-2-binding component 3 expression and might be a promising target for clinical non-small cell lung cancer therapy.

scholarly journals Inhibitory Effects of Furanocoumarins From the Roots of Angelica dahurica on Ionizing Radiation-Induced Migration of A549 Human Non-Small Cell Lung Cancer Cells

2020 ◽  
Vol 15 (4) ◽  
pp. 1934578X2091503
Author(s):  
Sang Hoon Lee ◽  
Ah-Reum Han ◽  
Unwoo Kang ◽  
Jin-Baek Kim ◽  
Eun Kyoung Seo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Ionizing Radiation ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Cancer Metastasis ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Angelica Dahurica ◽  
Small Cell Lung

Radiation therapy is a very effective tool for the treatment of advanced human lung cancers. However, as one of its malignancy-promoting behaviors, ionizing radiation (IR) increases cell migration and radiation resistance in several lung cancer cells, including non-small cell lung cancer (NSCLC) cells. As part of our ongoing search for potent radiotherapy enhancers from medicinal herbs, a chloroform-soluble fraction of the roots of Angelica dahurica was subjected to phytochemical investigation, leading to the isolation of 8 furanocoumarins. Of these, psoralen (1), xanthotoxin (2), and bergapten (3) inhibited IR-induced migration at a non-cytotoxic concentration (50 μM) in human NSCLC A549 cells. This study is the first to report on the inhibitory activities of these constituents of A. dahurica against IR-induced cancer metastasis.

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