microRNA-451 (miR-451) Regulates the Apoptosis of Non-Small Cell Lung Cancer Cells by Targeting Macrophage Migration Promoting Factors

2021 ◽  
Vol 11 (7) ◽  
pp. 1388-1393
Author(s):  
Caihong Wei ◽  
Dan Guo ◽  
Huayun Pu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
Cell Number ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Blank Group ◽  
High Expression Group

MicroRNA (miRNA) participates in cellular activities. This article mainly discusses whether miR-451 has a role in the apoptosis of non-small cell lung cancer (NSCLC) cells. A549 cell was divided into blank group, miR-451 overexpression group and NC group followed by analysis of level of miR-451, MIF mRNA, MIF, NF-κB, and nuclear expression of NF-κB by immunofluorescence, clone formation, cell apoptosis rate and cell cycle. miR-451 overexpression significantly inhibited MIF and NF-κB expression. In the case of miR-451 overexpression, NSCLC clone formation was inhibited time-dependently The nuclear NF-κB expression in miR451 group was significantly inhibited, indicating inhibition of MIF by miR-451, leading to inhibition of NSCLC cell proliferation. Further results showed that cell apoptotic rate of miR-451 high expression group was elevated with increased cell number in G2 phase, confirming that miR-451 overexpression promoted NSCLC cell apoptosis. miR-451 over-expression can inhibit MIF level by inhibiting NF-κB signaling pathway, thereby promoting NSCLC cell apoptosis, providing a new therapeutic approach for the clinical targeted therapy.

scholarly journals GDC-0349 inhibits non-small cell lung cancer cell growth

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Han Yang ◽  
Jun Zhao ◽  
Mengjing Zhao ◽  
Lihao Zhao ◽  
Li-na Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
A549 Cells ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Jnk Activation

Abstract Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related human mortality with a clear need for new therapeutic intervention. GDC-0349 is a potent and selective ATP-competitive mTOR inhibitor. In A549 cells and primary human NSCLC cells, GDC-0349 inhibited cell growth, proliferation, cell cycle progression, migration and invasion, while inducing significant apoptosis activation. Although GDC-0349 blocked Akt-mTORC1/2 activation in NSCLC cells, it also exerted cytotoxicity in Akt1-knockout A549 cells. Furthermore, restoring Akt-mTOR activation by a constitutively-active Akt1 only partially attenuated GDC-0349-induced A549 cell apoptosis, indicating the existence of Akt-mTOR-independent mechanisms. In NSCLC cells GDC-0349 induced sphingosine kinase 1 (SphK1) inhibition, ceramide accumulation, JNK activation and oxidative injury. Conversely, N-acetylcysteine, the JNK inhibitor and sphingosine 1-phosphate alleviated GDC-0349-induced NSCLC cell apoptosis. In vivo, daily oral administration of GDC-0349 potently inhibited NSCLC xenograft growth in mice. Akt-mTOR in-activation, SphK1 inhibition, JNK activation and oxidative stress were detected in NSCLC xenograft tissues with GDC-0349 administration. In summary, GDC-0349 inhibits NSCLC cell growth via Akt-mTOR-dependent and Akt-mTOR-independent mechanisms.

The Key microRNAs Regulated the Development of Non-small Cell Lung Cancer by Targeting TGF-β-induced epithelial–mesenchymal Transition

2019 ◽  
Vol 22 (4) ◽  
pp. 238-244 ◽  
Author(s):  
Gang Chen ◽  
Bo Ye
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Purpose: Epithelial-to-Mesenchymal Transition (EMT) was reported to play a key role in the development of Non-Small Cell Lung Cancer (NSCLC). The process of EMT is regulated by the changes of miRNAs expression. However, it is still unknown which miRNA changed the most in the process of canceration and whether these changes played a role in tumor development. Methods: A total of 36 SCLC patients treated in our hospital between 11th, 2015 and 10th, 2017 were enrolled. The samples of cancer tissues and paracancer tissues of patients were collected and analyzed. Then, the miRNAs in normal lung cells and NSCLC cells were also analyzed. In the presence of TGF-β, we transfected the miRNA mimics or inhibitor into NSCLC cells to investigate the role of the significantly altered miRNAs in cell migration and invasion and in the process of EMT. Results: MiR-330-3p was significantly up-regulated in NSCLC cell lines and tissues and miRNA- 205 was significantly down-regulated in NSCLC cell lines and NSCLC tissues. Transfected miRNA-205 mimics or miRMA-330-3p inhibitor inhibited the migration and invasion of NCIH1975 cell and restrained TGF-β-induced EMT in NSCLC cells. Conclusion: miRNA-330-3p and miRNA-205 changed the most in the process of canceration in NSCLC. Furthermore, miR-330-3p promoted cell invasion and metastasis in NSCLC probably by promoting EMT and miR-205 could restrain NSCLC likely by suppressing EMT.

scholarly journals Midazolam increases cisplatin-sensitivity in non-small cell lung cancer (NSCLC) via the miR-194-5p/HOOK3 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tingting Sun ◽  
Jing Chen ◽  
Xuechao Sun ◽  
Guonian Wang
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
Cisplatin Resistance ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Cisplatin Sensitivity

Abstract Backgrounds As previously reported, midazolam anesthesia exerts tumor-suppressing effects in non-small cell lung cancer (NSCLC), but the regulating effects of this drug on cisplatin-resistance in NSCLC have not been studied. Thus, we designed this study to investigate this issue and preliminarily delineate the potential molecular mechanisms. Methods We performed MTT assay and trypan blue staining assay to measure cell proliferation and viability. Cell apoptosis was examined by FCM. qRT-PCR and immunoblotting were performed to determine the expression levels of genes. The targeting sites between genes were predicted by bioinformatics analysis and were validated by dual-luciferase reporter gene system assay. Mice tumor-bearing models were established and the tumorigenesis was evaluated by measuring tumor weight and volume. Immunohistochemistry (IHC) was used to examine the pro-proliferative Ki67 protein expressions in mice tumor tissues. Results The cisplatin-resistant NSCLC (CR-NSCLC) cells were treated with high-dose cisplatin (50 μg/ml) and low-dose midazolam (10 μg/ml), and the results showed that midazolam suppressed cell proliferation and viability, and promoted cell apoptosis in cisplatin-treated CR-NSCLC cells. In addition, midazolam enhanced cisplatin-sensitivity in CR-NSCLC cell via modulating the miR-194-5p/hook microtubule-tethering protein 3 (HOOK3) axis. Specifically, midazolam upregulated miR-194-5p, but downregulated HOOK3 in the CR-NSCLC cells, and further results validated that miR-194-5p bound to the 3’ untranslated region (3’UTR) of HOOK3 mRNA for its inhibition. Also, midazolam downregulated HOOK3 in CR-NSCLC cells by upregulating miR-194-5p. Functional experiments validated that both miR-194-5p downregulation and HOOK3 upregulation abrogated the promoting effects of midazolam on cisplatin-sensitivity in CR-NSCLC cells. Conclusions Taken together, this study found that midazolam anesthesia reduced cisplatin-resistance in CR-NSCLC cells by regulating the miR-194-5p/HOOK3 axis, implying that midazolam could be used as adjuvant drug for NSCLC treatment in clinical practices.

scholarly journals Tin Mesoporphyrin Selectively Reduces Non-Small-Cell Lung Cancer Cell Line A549 Proliferation by Interfering with Heme Oxygenase and Glutathione Systems

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 917
Author(s):  
Valeria Sorrenti ◽  
Agata Grazia D’Amico ◽  
Ignazio Barbagallo ◽  
Valeria Consoli ◽  
Salvo Grosso ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Heme Oxygenase ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Antioxidant Systems ◽  
Nsclc Cell Line ◽  
Small Cell Lung

In order to maintain redox homeostasis, non-small-cell lung cancer (NSCLC) increases the activation of many antioxidant systems, including the heme-oxygenase (HO) system. The overexpression of HO-1 has been often associated with chemoresistance and tumor aggressiveness. Our results clearly showed an overexpression of the HO-1 protein in A549 NSCLC cell lines compared to that in non-cancerous cells. Thus, we hypothesized that “off-label” use of tin mesoporphyrin, a well-known HO activity inhibitor clinically used for neonatal hyperbilirubinemia, has potential use as an anti-cancer agent. The pharmacological inhibition of HO activity caused a reduction in cell proliferation and migration of A549. SnMP treatment caused an increase in oxidative stress, as demonstrated by the upregulation of reactive oxygen species (ROS) and the depletion of glutathione (GSH) content. To support these data, Western blot analysis was performed to analyze glucose-6-phosphate dehydrogenase (G6PD), TP53-induced glycolysis and the apoptosis regulator (TIGAR), and the glutamate cysteine ligase catalytic (GCLC) subunit, as they represent the main regulators of the pentose phosphate pathway (PPP) and glutathione synthesis, respectively. NCI-H292, a subtype of the NSCLC cell line, did not respond to SnMP treatment, possibly due to low basal levels of HO-1, suggesting a cellular-dependent antitumorigenic effect. Altogether, our results suggest HO activity inhibition may represent a potential target for selective chemotherapy in lung cancer subtypes.

scholarly journals Small-molecule inhibition of APE1 induces apoptosis, pyroptosis, and necroptosis in non-small cell lung cancer

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Kaili Long ◽  
Lili Gu ◽  
Lulu Li ◽  
Ziyu Zhang ◽  
Enjie Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Molecular Compound ◽  
Small Cell Lung

AbstractApurinic/apyrimidinic endonuclease 1 (APE1) plays a critical role in the base excision repair (BER) pathway, which is responsible for the excision of apurinic sites (AP sites). In non-small cell lung cancer (NSCLC), APE1 is highly expressed and associated with poor patient prognosis. The suppression of APE1 could lead to the accumulation of unrepaired DNA damage in cells. Therefore, APE1 is viewed as an important marker of malignant tumors and could serve as a potent target for the development of antitumor drugs. In this study, we performed a high-throughput virtual screening of a small-molecule library using the three-dimensional structure of APE1 protein. Using the AP site cleavage assay and a cell survival assay, we identified a small molecular compound, NO.0449-0145, to act as an APE1 inhibitor. Treatment with NO.0449-0145 induced DNA damage, apoptosis, pyroptosis, and necroptosis in the NSCLC cell lines A549 and NCI-H460. This inhibitor was also able to impede cancer progression in an NCI-H460 mouse model. Moreover, NO.0449-0145 overcame both cisplatin- and erlotinib-resistance in NSCLC cell lines. These findings underscore the importance of APE1 as a therapeutic target in NSCLC and offer a paradigm for the development of small-molecule drugs that target key DNA repair proteins for the treatment of NSCLC and other cancers.

scholarly journals Comprehensive analysis of prognostic value and immune infiltration of kindlin family members in non-small cell lung cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiaoshan Su ◽  
Ning Liu ◽  
Weijing Wu ◽  
Zhixing Zhu ◽  
Yuan Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Immune Infiltration

Abstract Background Kindlin Family Members have been reported to be aberrantly expressed in various human cancer types and involved in tumorigenesis, tumor progression, and chemoresistance. However, their roles in non-small cell lung cancer (NSCLC) remain poorly elucidated. Methods We analyzed the prognostic value and immune infiltration of Kindlins in NSCLC through Oncomine, GEPIA, UALCAN, CCLE, Kaplan‑Meier plotter, cBioPortal, TIMER, GeneMANIA, STRING, and DAVID database. Additionally, the mRNA expression levels of Kindlins were verified in 30 paired NSCLC tissues and NSCLC cell lines by real-time PCR. Results The expression level of FERMT1 was remarkably increased in NSCLC tissues and NSCLC cell lines, while FERMT2 and FERMT3 were reduced. Kindlins expressions were associated with individual cancer stages and nodal metastasis. We also found that higher expression level of FERMT1 was obviously correlated with worse overall survival (OS) in patients with NSCLC, while higher FERMT2 was strongly associated with better overall survival (OS) and first progression (FP). Additionally, the expression of FERMT2 and FERMT3 were obviously correlated with the immune infiltration of diverse immune cells. Functional enrichment analysis has shown that Kindlins may be significantly correlated with intracellular signal transduction, ATP binding and the PI3K-Akt signaling pathway in NSCLC. Conclusions The research provides a new perspective on the distinct roles of Kindlins in NSCLC and likely has important implications for future novel biomarkers and therapeutic targets in NSCLC.

scholarly journals Expression Profiles of microRNAs in Drug-Resistant Non-Small Cell Lung Cancer Cell Lines Using microRNA Sequencing

2018 ◽  
Vol 51 (6) ◽  
pp. 2509-2522 ◽  
Author(s):  
Shousen Hu ◽  
Yongliang Yuan ◽  
Zhizhen Song ◽  
Dan Yan ◽  
Xiangzhen Kong
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Expression Profiles ◽  
Small Cell ◽  
Nsclc Cell ◽  
Drug Resistant ◽  
Small Cell Lung

Background/Aims: Drug resistance remains a main obstacle to the treatment of non- small cell lung cancer (NSCLC). The aim of this study was to identify the expression profiles of microRNAs (miRNAs) in drug-resistant NSCLC cell lines. Methods: The expression profiles of miRNAs in drug-resistant NSCLC cell lines were examined using miRNA sequencing, and the common dysregulated miRNAs in these cell lines were identified and analyzed by bioinformatics methods. Results: A total of 29 upregulated miRNAs and 36 downregulated miRNAs were found in the drug-resistant NSCLC cell lines, of which 26 upregulated and 36 downregulated miRNAs were found to be involved in the Ras signaling pathway. The expression levels, survival analysis, and receiver operating characteristic curve of the dysregulated miRNAs based on The Cancer Genome Atlas database for lung adenocarcinoma showed that hsa-mir-192, hsa-mir-1293, hsa-mir-194, hsa-mir-561, hsa-mir-205, hsa-mir-30a, and hsa-mir-30c were related to lung cancer, whereas only hsa-mir-1293 and hsa-mir-561 were not involved in drug resistance. Conclusion: The results of this study may provide novel biomarkers for drug resistance in NSCLC and potential therapies for overcoming drug resistance, and may also reveal the potential mechanisms underlying drug resistance in this disease.

scholarly journals Circular RNA circPVT1 Promotes Proliferation and Invasion Through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer

2018 ◽  
Vol 51 (5) ◽  
pp. 2324-2340 ◽  
Author(s):  
Xiuyuan Li ◽  
Zenglei Zhang ◽  
Hua Jiang ◽  
Qiang Li ◽  
Ruliang Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Promoter Region ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Proliferation And Invasion

Background/Aims: Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers, however its role in non-small cell lung cancer (NSCLC) tumorigenesis is not well understood. The aim of this study is to identify the expression level of circPVT1 in NSCLC and further investigated its functional relevance with NSCLC progression both in vitro and in vivo. Methods: Quantative real-time PCR was used for the measurement of circPVT1 in NSCLC specimens and cell lines. Fluorescence in situ hybridization analysis (FISH) assay was used for the identification of sublocation of circPVT1 in NSCLC cells. Bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to verify the binding of c-Fos at circPVT1 promoter region, and the direct interaction between circPVT1 and miR-125b. Gain- or loss-function assays were performed to evaluate the effects of circPVT1 on cell proliferation and invasion. Western blot and immunohistochemistry assays were performed to detect the protein levels involved in E2F2 pathway. Results: We found that circPVT1 was upregulated in NSCLC specimens and cells. The transcription factor c-Fos binded to the promoter region of circPVT1, resulting in the overexpression of circPVT1 in NSCLC. Knockdown of circPVT1 suppressed NSCLC cell proliferation, migration and invasion, and increased apoptosis. In addition, circPVT1 mediated NSCLC progression via the regulation of E2F2 signaling pathway. More importantly, circPVT1 was predominantly abundant in the cytoplasm of NSCLC cells, and circPVT1 could serve as a competing endogenous RNA to regulate E2F2 expression and tumorigenesis in a miR-125b-dependent manner, which is further verified by using an in vivo xenograft model. Conclusion: circPVT1 promotes NSCLC cell growth and invasion, and may serve as a promising therapeutic target for NSCLC patients. Therefore, silence of circPVT1 could be a future direction to develop a novel treatment strategy.

scholarly journals High levels of MESP1 expression in non-small cell lung cancer can facilitate cell proliferation, metastasis and suppresses cell apoptosis

2020 ◽  
Vol 9 (10) ◽  
pp. 5956-5968
Author(s):  
Lei Wang ◽  
Chunyan Yang ◽  
Fangfang Li ◽  
Dengcai Mu ◽  
Pengzhan Ran ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
Small Cell ◽  
Small Cell Lung
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