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 MicroRNA-510 Plays Oncogenic Roles in Non-Small Cell Lung Cancer by Directly Targeting SRC Kinase Signaling Inhibitor 1

2019 ◽  
Vol 27 (8) ◽  
pp. 879-887 ◽  
Author(s):  
Wei Wu ◽  
Linyan He ◽  
Yan Huang ◽  
Likun Hou ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Kinase Signaling ◽  
Small Cell Lung ◽  
Proliferation And Invasion

An increasing number of studies have demonstrated that microRNAs (miRNAs) may play key roles in various cancer carcinogenesis and progression, including non-small cell lung cancer (NSCLC). However, the expressions, roles, and mechanisms of miR-510 in NSCLC have, up to now, been largely undefined. In vivo assay showed that miR-510 was upregulated in NSCLC tissues compared with that in adjacent nontumor lung tissues. miR-510 expression was significantly correlated with TNM stage and lymph node metastasis. In vitro assay indicated that expressions of miR-510 were also increased in NSCLC cell lines. Downregulation of miR-510 suppressed NSCLC cell proliferation and invasion in vitro. We identified SRC kinase signaling inhibitor 1 (SRCIN1) as a direct target gene of miR-510 in NSCLC. Expression of SRCIN1 was downregulated in lung cancer cells and negatively correlated with miR-510 expression in tumor tissues. Downregulation of SRCIN1, leading to inhibition of miR-510 expression, reversed cell proliferation and invasion in NSCLC cells. These results showed that miR-510 acted as an oncogenic miRNA in NSCLC, partly by targeting SRCIN1, suggesting that miR-510 can be a potential approach for the treatment of patients with malignant lung cancer.

Hsa_circ_0003288 facilitates tumor progression by targeting miR-145 in non–small cell lung cancer cells

2021 ◽  
pp. 1-9
Author(s):  
Li-Na Pan ◽  
Yun-Fang Ma ◽  
Jia-An Hu ◽  
Zhi-Hong Xu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

Circular RNA (circRNA) has been shown to participate in various tumors, including lung cancer. In the present study, we explored the expression and functional relevance of hsa_circ_0003288 in human non-small cell lung cancer (NSCLC). We verified that hsa_circ_0003288 expression was upregulated in lung cancer tissues and cell lines. Overexpression of hsa_circ_0003288 dramatically promoted lung cancer cell proliferation, colony formation, inhibited apoptosis, and increased cell migration and invasion in vitro. Xenograft experiments showed that hsa_circ_0003288 overexpression accelerated tumor growth in vivo. Mechanistically, hsa_circ_0003288 negatively regulated miR-145 to exert the oncogenic role in lung cancer. Overexpression of miR-145 decreased cell proliferation, induced apoptosis, and suppressed migration and invasion in lung cancer. Additionally, miR-145 co-transfection abolished the oncogenic role of hsa_circ_0003288. Collectively, these findings identified a novel regulatory role of hsa_circ_0003288/miR-145 axis in the progression of NSCLC.

scholarly journals Tumor-associated calcium signal transducer 2 regulates neovascularization of non-small-cell lung cancer via activating ERK1/2 signaling pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769432 ◽  
Author(s):  
Xiaobin Guo ◽  
Xiaoming Zhu ◽  
Limin Zhao ◽  
Xiao Li ◽  
Dongjun Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Calcium Signal ◽  
Small Cell Lung

Lung cancer, especially the non-small-cell lung cancer, is a highly aggressive vascular cancer with excessively activated signaling pathways. Tumor-associated calcium signal transducer 2, also known as trop2, was identified to be correlated with tumor proliferation and invasion of non-small-cell lung cancer; however, the biological role of trop2 in neovascularization of non-small-cell lung cancer remained elusive. In this study, we first verified that trop2 was overexpressed in non-small-cell lung cancer tissues as well as cell lines and that the increased expression of trop2 promoted non-small-cell lung cancer cell proliferation and invasion. Then, we expanded the biological role of trop2 by in vitro and in vivo angiogenesis assay. The tubular formation analysis revealed that trop2 promoted non-small-cell lung cancer angiogenesis in vitro, and the immunohistochemistry staining of vascular markers (CD31 and CD34) provided evidences that trop2 promoted in vivo neovascularization. The results of polymerase chain reaction array revealed that trop2 promoted the expression level of two well-known angiogenesis factors MMP13 and PECAM1. By screening the trop2-related signaling pathways, we observed that excessive angiogenesis was correlated with activation of ERK1/2 signaling pathway, and ERK1/2 inhibitor (U0126) could suppress the tubular formation ability induced by trop2 expression. These results suggested that trop2 facilitated neovascularization of non-small-cell lung cancer via activating ERK1/2 signaling pathway. Targeting trop2 might provide novel anti-angiogenesis strategy for non-small-cell lung cancer treatment.

scholarly journals PELP1 expressed in non-small cell lung cancer and promotes tumor cell proliferation, metastasis, and drug resistance through MAPK signaling pathway.

2020 ◽  
Author(s):  
Xingen Wang ◽  
Weihua Ying ◽  
Li Liang
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Kinase Inhibitor ◽  
Small Cell ◽  
Small Cell Lung

Abstract Background Lung cancer is one of the tumors with high morbidity and mortality among males and females worldwide. Proline-, glutamic acid-, and leucine-rich protein 1(PELP1) is an estrogen receptor coactivator and functions as a scaffolding protein. Its oncogenic signaling was involved in the progression of several cancers. However, there is little known about the role of PELP1 in the lung cancer. The aim of this study is to explore the role of PELP1 in non-small cell lung cancer. Methods The expression of PELP1 in microarrays of lung cancer tissue and correlation with clinicopathological parameters were performed. RNA interference technology was used to downregulate PELP1 expression in A549 lung cancer cells and the tumor cell’s ability of proliferation, migration, invasion was detected by Cell Count Kit-8 and trans-well essay. In addition, whole genome exon was analyzed by poly-A RNA-sequencing. Results Results showed that PELP1 is overexpressed in the lung cancer specimens and its expression correlate with histological type, smoking status, and EGFR status but no significant prognostic value. Knockdown of PELP1 inhibited cell proliferation, migration, invasion of lung cancer cells. Furthermore, silencing PELP1 in lung tumor cells promotes the sensitivity of tumor cells to the tyrosine kinase inhibitor Gefitinib. RNA-sequencing and Western-blotting found that 140 genes were up-regulated and 143 genes were down-regulated in PELP1 silenced lung adenocarcinoma cells, which mainly affected the mitogen-activated protein kinase (MAPK) signal pathway, EGFR tyrosine kinase inhibitor resistance, PPAR signaling pathway, Cytosolic DNA-sensing pathway, cytokine-cytokine receptor interaction, drug metabolism, cAMP signaling pathway, RIG-1-like receptor signaling pathway. Conclusions PELP1 plays a key role in non-small cell lung cancer proliferation, progression, and drug resistance. These results suggest that PELP1 could be a potential target for therapeutic intervention for lung cancer.

PYGB facilitates cell proliferation and invasiveness in non-small cell lung cancer by activating the Wnt–β-catenin signaling pathway

2020 ◽  
Vol 98 (5) ◽  
pp. 565-574 ◽  
Author(s):  
Lina Xiao ◽  
Wei Wang ◽  
Qiuqiang Huangfu ◽  
Hongjie Tao ◽  
Jingyi Zhang
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Wnt Signaling Pathway ◽  
Positive Lymph Node ◽  
Small Cell ◽  
Small Cell Lung

Brain-type glycogen phosphorylase (PYGB) has been correlated with the progression of various human malignancies; however, its effects and regulatory mechanisms in non-small cell lung cancer (NSCLC) are still unclear. We used Western blotting, immunohistochemistry, and qRT-PCR to verify that the protein and mRNA expression levels of PYGB are up-regulated in both NSCLC cell lines and tissues. The expression of PYGB was positively related to TNM stage, positive lymph node metastasis, and poor prognosis in patients with NSCLC. Moreover, overexpression of PYGB promoted cell proliferation, migration, and invasiveness, but inhibited apoptosis, in vitro. Immunofluorescence assays showed that overexpression of PYGB promoted the nuclear import and accumulation of β-catenin. By comparison, silencing PYGB produced the opposite effects. Further, overexpression of PYGB resulted in activation of the Wnt signaling pathway, and transfection with Sh-PYGB produced the opposite effect, and these effects were abrogated by XAV-939 (a β-catenin inhibitor) or overexpression of β-catenin, respectively. Finally, knockdown of PYGB inhibited tumor growth in a mouse model of xenograft tumors. These findings highlight the role of PYGB in the progression of NSCLC, and reveal a link between PYGB and the Wnt–β-catenin signaling pathway, thus providing a new potential target for treatment of NSCLC.

scholarly journals PELP1 Expressed in Non-Small Cell Lung Cancer and Promotes Tumor Cell Proliferation, Metastasis, and Drug Resistance Through MAPK Signaling Pathway.

2020 ◽  
Author(s):  
Xingen Wang ◽  
Weihua Ying ◽  
Li Liang
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Kinase Inhibitor ◽  
Small Cell ◽  
Small Cell Lung

Abstract Background Lung cancer is one of the tumors with high morbidity and mortality among males and females worldwide. Proline-, glutamic acid-, and leucine-rich protein 1(PELP1) is an estrogen receptor coactivator and functions as a scaffolding protein. Its oncogenic signaling was involved in the progression of several cancers. However, there is little known about the role of PELP1 in the lung cancer. The aim of this study is to explore the role of PELP1 in non-small cell lung cancer. Methods The expression of PELP1 in microarrays of lung cancer tissue and correlation with clinicopathological parameters were performed. RNA interference technology was used to downregulate PELP1 expression in A549 lung cancer cells and the tumor cell’s ability of proliferation, migration, invasion was detected by Cell Count Kit-8 and trans-well essay. In addition, whole genome exon was analyzed by poly-A RNA-sequencing. Results Results showed that PELP1 is overexpressed in the lung cancer specimens and its expression correlate with histological type, smoking status, and EGFR status but no significant prognostic value. Knockdown of PELP1 inhibited cell proliferation, migration, invasion of lung cancer cells. Furthermore, silencing PELP1 in lung tumor cells promotes the sensitivity of tumor cells to the tyrosine kinase inhibitor Gefitinib. RNA-sequencing and Western-blotting found that 140 genes were up-regulated and 143 genes were down-regulated in PELP1 silenced lung adenocarcinoma cells, which mainly affected the mitogen-activated protein kinase (MAPK) signal pathway, EGFR tyrosine kinase inhibitor resistance, PPAR signaling pathway, Cytosolic DNA-sensing pathway, cytokine-cytokine receptor interaction, drug metabolism, cAMP signaling pathway, RIG-1-like receptor signaling pathway. Conclusions PELP1 plays a key role in non-small cell lung cancer proliferation, progression, and drug resistance. These results suggest that PELP1 could be a potential target for therapeutic intervention for lung cancer.

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 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.

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