ID: 130: NOVEL ROLE FOR LYSOCARDIOLIPIN ACYLTRANSFERASE (LYCAT) IN NON-SMALL CELL LUNG CANCER

2016 ◽  
Vol 64 (4) ◽  
pp. 971.1-971 ◽  
Author(s):  
MM Van Scoyk ◽  
S Avasarala ◽  
RA Winn ◽  
R Bikkavilli ◽  
V Natarajan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Epithelial Cell ◽  
Cell Lines ◽  
Mitochondrial Dynamics ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Epithelial Cell Lines

Lung cancer is the leading cause of deaths in United States and non-small cell lung cancer (NSCLC) accounts for ∼85% of all lung cancers with a 5-year survival rate of approximately ∼16%. Therefore there is an immediate need to develop new strategies for early detection and more effective treatments options. Mitochondrial dysfunction including but not limited to defects in mitochondrial genomics and dynamics has long been implicated to play a role in human health and disease particularly in cancer initiation, progression and treatment options since it plays a pivotal role in cell death and survival. Lysocardiolipin acyltransferase (LYCAT), a Cardiolipin remodeling enzyme regulating the 18:2 linoleic acid pattern of mammalian mitochondrial cardiolipin, plays a crucial role in maintaining normal mitochondrial function and vascular development. LYCAT was shown to be up-regulated in cancers; however, the role of LYCAT in lung cancer is yet unclear. Probing the protein expression of LYCAT in lung cancer specimens, non-transformed bronchial epithelial cell lines and 5 lung cancer cell lines revealed increased LYCAT expression and activity in all the lung cancer samples and cell lines tested in comparison to the control lung tissues and non-transformed epithelial cell lines. To determine the role of LYCAT in lung cancer, NSCLC cell lines H2122 and H23 were transfected with either scrambled or LYCAT shRNA and differences in serum-induced cell proliferation, migration, clonogenecity and mitochondrial dynamics were determined. Our results demonstrated that down-regulation of LYCAT by shRNA significantly attenuated cell migration, proliferation, and invasion in NSCLC cell lines compared to control cell lines. Furthermore knockdown of LYCAT expression in NSCLC cell lines inhibited mitochondrial fragmentation and enhanced mitochondrial fusion. Taken together, these data demonstrate a strong association between increased LYCAT expression and cell proliferation, motility, invasion and mitochondrial dynamics in NSCLC cells. Thus, development of targeted therapies to reduce LYCAT expression in NSCLC should be beneficial. This work in part was supported by funds from the College of Medicine, UIC and NIH HL98050 to VN.

scholarly journals MiR-761 Promotes Progression and Metastasis of Non-Small Cell Lung Cancer by Targeting ING4 and TIMP2

2015 ◽  
Vol 37 (1) ◽  
pp. 55-66 ◽  
Author(s):  
An Yan ◽  
Chunyu Yang ◽  
Zhibo Chen ◽  
Chunhong Li ◽  
Li Cai
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Proliferation And Metastasis ◽  
Metastatic Activity

Background/Aims: The aim of this study was to investigate the role of microRNA miR-761 in the progression and metastasis of non-small cell lung cancer (NSCLC), and the mechanisms by which miR-761 regulates cell proliferation and metastatic activity of NSCLC cell lines. Methods: Quantitative real-time PCR (qRT-PCR) was used to assess miR-761 expression in NSCLC serum and tissue. MTT, wound healing, and transwell assays were performed to examine the role of miR-761 in regulation of cell proliferation and metastatic activity in NSCLC cell lines. In addition, the correlations of miR-761 expression with clinical-pathologic factors were statistically analyzed. Finally, we investigated whether miR-761 promotes proliferation and metastasis in NSCLC cell lines by targeting ING4 (inhibitor of growth family, member 4) and TIMP2 (tissue inhibitor of metalloproteinase 2). Results: MiR-761 was significantly upregulated in both NSCLC serum and tissues as compared to normal participants and paired noncancerous tissues respectively. Ectopic expression of miR-761 promoted cell proliferation and metastasis in H460 cells, while miR-761 inhibitor reduced proliferation rates and metastasis in H23 cells. Furthermore, luciferase reporter assay and functional analyses indicated that miR-761 directly targeted ING4 and TIMP2. Conclusion: miR-761 promotes progression and metastasis of NSCLC by targeting ING4 and TIMP2.

scholarly journals Nicotine promotes the development of non-small cell lung cancer through activating LINC00460 and PI3K/Akt signaling

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Hongying Zhao ◽  
Yu Wang ◽  
Xiubao Ren
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Akt Signaling ◽  
Small Cell ◽  
Nsclc Cell ◽  
Expression Level ◽  
In Vitro Experiments ◽  
Small Cell Lung

Abstract Objective: Nicotine, the main ingredient in tobacco, is identified to facilitate tumorigenesis and accelerate metastasis in tumor. Studies in recent years have reported that long intergenic non-protein coding RNA 460 (LINC00460) is strongly associated with lung cancer poor prognosis and nicotine dependence. Nonetheless, it is unclear whether nicotine promotes the development of lung cancer through activation of LINC00460. Methods: We determined that LINC00460 expression in lung cancer tissues and the prognosis in patients with non-small cell lung carcinoma (NSCLC) using Gene Expression Profiling Interactive Analysis (GEPIA) website and The Cancer Genome Atlas (TCGA) database. Through in vitro experiments, we studied the effects of nicotine on LINC00460 in NSCLC cells lines using Cell Counting Kit-8 (CCK-8), transwell test, flow cytometry, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot assays. Results: We identified the significant up-regulated expression level of LINC00460 in NSCLC tissues and cell lines, especially, the negative correlation of LINC00460 expression level with overall survival (OS). In in vitro experiments, LINC00460 was overexpressed in NSCLC cell lines under nicotine stimulation. Nicotine could relieve the effect of LINC00460 knockdown on NSCLC cell proliferation, migration and apoptosis. The same influence was observed on PI3K/Akt signaling pathway. Conclusions: In summary, this is the first time to examine the potential roles of LINC00460 in lung cancer cell proliferation, migration and apoptosis induced by nicotine. This may help to develop novel therapeutic strategies for the prevention and treatment of metastatic tumors from cigarette smoke-caused lung cancer by blocking the nicotine-activated LINC00460 pathway.

scholarly journals Long noncoding RNA HOXA-AS2 promotes non-small cell lung cancer progression by regulating miR-520a-3p

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Yunpeng Liu ◽  
Xingyu Lin ◽  
Shiyao Zhou ◽  
Peng Zhang ◽  
Guoguang Shao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract Background: The HOXA cluster antisense RNA 2 (HOXA-AS2) has recently been discovered to be involved in carcinogenesis in multiple cancers. However, the role and underlying mechanism of HOXA-AS2 in non-small cell lung cancer (NSCLC) yet need to be unraveled. Methods: HOXA-AS2 expression in NSCLC tissues and cell lines was detected using quantitative real-time PCR (qRT-PCR). Furthermore, the effects of HOXA-AS2 on NSCLC cell proliferation, apoptosis, migration, and invasion were assessed by MTS, flow cytometry, wound healing and transwell invasion assays, respectively. Starbase2.0 predicted and luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the association of HOXA-AS2 and miR-520a-3p in NSCLC cells. Results: Our results revealed that HOXA-AS2 in NSCLC tissues were up-regulated and cell lines, and were associated with poor prognosis and overall survival. Further functional assays demonstrated that HOXA-AS2 knockdown significantly inhibited NSCLC cell proliferation, induced cell apoptosis and suppressed migration and invasion. Starbase2.0 predicted that HOXA-AS2 sponge miR-520a-3p at 3′-UTR, which was confirmed using luciferase reporter and RIP assays. miR-520a-3p expression was inversely correlated with HOXA-AS2 expression in NSCLC tissues. In addition, miR-520a-3p inhibitor attenuated the inhibitory effect of HOXD-AS2-depletion on cell proliferation, migration and invasion of NSCLC cells. Moreover, HOXA-AS2 could regulate HOXD8 and MAP3K2 expression, two known targets of miR-520a-3p in NSCLC. Conclusion: These findings implied that HOXA-AS2 promoted NSCLC progression by regulating miR-520a-3p, suggesting that HOXA-AS2 could serve as a therapeutic target for NSCLC.

scholarly journals KPNB1-mediated nuclear translocation of PD-L1 promotes non-small cell lung cancer cell proliferation via the Gas6/MerTK signaling pathway

2020 ◽  
Author(s):  
Wenwen Du ◽  
Jianjie Zhu ◽  
Yuanyuan Zeng ◽  
Ting Liu ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung

Abstract In addition to the role of programmed cell death ligand 1 (PD-L1) in facilitating tumour cells escape from immune surveillance, it is considered as a crucial effector in transducing intrinsic signals to promote tumour development. Our previous study has pointed out that PD-L1 promotes non-small cell lung cancer (NSCLC) cell proliferation, but the mechanism remains elusive. Here we first demonstrated that PD-L1 expression levels were positively correlated with p-MerTK levels in patient samples and NSCLC cell lines. In addition, PD-L1 knockdown led to the reduced phosphorylation level of MerTK in vitro. We next showed that PD-L1 regulated NSCLC cell proliferation via Gas6/MerTK signaling pathway in vitro and in vivo. To investigate the underlying mechanism, we unexpectedly found that PD-L1 translocated into the nucleus of cancer cells which was facilitated through the binding of Karyopherin β1 (KPNB1). Nuclear PD-L1 (nPD-L1), coupled with transcription factor Sp1, regulated the synthesis of Gas6 mRNA and promoted Gas6 secretion to activate MerTK signaling pathway. Taken together, our results shed light on the novel role of nPD-L1 in NSCLC cell proliferation and reveal a new molecular mechanism underlying nPD-L1-mediated Gas6/MerTK signaling activation. All above findings provide the possible combinational implications for PD-L1 targeted immunotherapy in the clinic.

scholarly journals Overexpression of Wnt7a enhances radiosensitivity of non-small-cell lung cancer via the Wnt/JNK pathway

Biology Open ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. bio050575
Author(s):  
Pingping Ai ◽  
Xianhua Xu ◽  
Shijie Xu ◽  
Zhixia Wei ◽  
Shun Tan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

ABSTRACTThe Wingless-type protein 7a (Wnt7a) plays an antiproliferative role in non-small-cell lung cancer (NSCLC). Previous studies have indicated that Wnt7a expression was downregulated in radiation-resistant NSCLC cells. However, little is known about its biological functions and molecular mechanisms in radiosensitivity of NSCLC. Thus, NSCLC cell proliferation and apoptosis in response to Wnt7a overexpression and/or radiation were determined by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl-tertazolium bromide (MTT) assay and flow cytometry, respectively. The activation of the Wnt/cJun N-terminal kinase (JNK) and Wnt/β-catenin signaling pathways were further examined by western blot in NSCLC cell lines H1650 and A549. Wnt7a overexpression combined with radiation-inhibited cell proliferation and induced apoptosis in NSCLC cell lines compared to Wnt7a overexpression or radiotherapy alone. In addition, the phosphorylation of JNK, but not β-catenin, was congruent with the changes in Wnt7a overexpression and/or radiation. Moreover, the Wnt/JNK pathway could induce the apoptosis of NSCLC cells through the mitochondrial pathway. Inhibition of the Wnt/JNK signaling pathway by SP600125, a JNK inhibitor, contributed to proliferation induction in NSCLC cells. Taken together, these results showed that Wnt7a overexpression sensitized NSCLC cell lines to radiotherapy through the Wnt/JNK signaling pathway.

scholarly journals SRPX2 promotes cell proliferation and invasion via activating FAK/SRC/ERK pathway in non-small cell lung cancer

2020 ◽  
Author(s):  
Xiujuan Li ◽  
Jing Liu ◽  
Hong Sun ◽  
Yong Zou ◽  
Juan Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Underlying Mechanism ◽  
Small Cell ◽  
Migration And Invasion ◽  
Erk Pathway ◽  
Small Cell Lung

Background: Recent studies showed that sushi repeat containing protein X linked 2 (SRPX2) could participate in the development of various malignant tumors. However, its role in non-small cell lung cancer (NSCLC) was unknown. The aim of the study was to prospectively investigate the role of SRPX2 in NSCLC cell proliferation, migration and invasion and reveal the underlying mechanism. Material and methods: Quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry – IHC) were used to measure detect the mRNA and protein levels, respectively, in NSCLC tissues and cell lines. Cell Counting Kit-8 (CCK-8), colony formation, wound healing and transwell assays were utilized to assess cell proliferation, migration and invasion. In vivo subcutaneous xenograft tumor model was established to detect the tumorigenic function of SRPX2, and IHC assay was performed to measure protein expression. Results: SRPX2 expression was upregulated in NSCLC tissues and cell lines, and positively correlated with tumor size, lymph node metastasis, distant metastasis and clinical stage. High SRPX2 expression also predicted poor prognosis. In vitro experiments indicated that overexpression of SRPX2 promoted the proliferation, migration, and invasion of SPC-A1 cells while knockdown of SRPX2 caused the opposite effects in A549 cells. Specifically, SRPX2 activated FAK/SRC/ERK pathway and its downstream effectors and promoted epithelial-mesenchymal transition (EMT). Conclusion: Taken together, our findings revealed a functional role of SRPX2 in NSCLC cell proliferation, migration and invasion. The underlying mechanism was, at least partially, the activation of FAK/SRC/ERK pathway. This study provides the molecular basis for targeting SRPX2 in potential clinical application for NSCLC.

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.

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