scholarly journals miR-25 Promotes Cell Proliferation, Migration, and Invasion of Non-Small-Cell Lung Cancer by Targeting the LATS2/YAP Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Tangwei Wu ◽  
Hui Hu ◽  
Tianzhu Zhang ◽  
Liyuan Jiang ◽  
Xiaoyi Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cancer Metastasis ◽  
Small Cell ◽  
Nsclc Cell ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Lung Cancer Metastasis ◽  
Nsclc Patients

Metastasis is the leading cause of high mortality in lung cancer patients, and metastatic lung cancer is difficult to treat. miRNAs are involved in various biological processes of cancer, including metastasis. Our previous studies revealed that miR-25 promoted non-small-cell lung cancer (NSCLC) cell proliferation and suppressed cell apoptosis by directly targeting TP53 and MOAP1. In this work, we further explored the miR-25 expression in NSCLC patients in the Cancer Genome Atlas (TCGA) database and measured the miR-25 expression levels in the tissues of NSCLC patients and cell lines. miR-25 was overexpressed in both NSCLC tissues and cell lines. NSCLC patients who expressed a higher level of miR-25 exhibited worse overall survival than those with a lower level of miR-25. Overexpression of miR-25 enhanced NSCLC cell migration and invasion, while the inhibition of miR-25 exhibited the opposite effects. We identified the large tumor suppressor homology 2 (LATS2) as a new target gene of miR-25 in lung cancer. The effects of miR-25 on promoting NSCLC cell migration and invasion were at least partially due to activation of the Hippo signaling pathway. Additionally, miR-25 antagomir inhibited xenograft tumor growth and metastasis by the upregulation of LATS2. Taken together, our findings demonstrate that miR-25 contribute to lung cancer cell proliferation and metastasis by targeting the LATS2/YAP signaling pathway, which implicate miR-25 as a promising therapeutic target for lung cancer metastasis. Given that oxidative stress induces the overexpression of miR-25 and plays a critical role in cancer progression, this study establishes miR-25 as an intermediate between oxidative stress and lung cancer metastasis.

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 lncRNA AFAP1-AS1 Promotes Migration and Invasion of Non-Small Cell Lung Cancer via Up-Regulating IRF7 and the RIG-I-Like Receptor Signaling Pathway

2018 ◽  
Vol 50 (1) ◽  
pp. 179-195 ◽  
Author(s):  
Xiao-Di Tang ◽  
Duo-Duo Zhang ◽  
Linpei Jia ◽  
Wei Ji ◽  
Yu-Shuang  Zhao
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Migration And Invasion ◽  
Receptor Signaling ◽  
Small Cell Lung ◽  
Receptor Signaling Pathway

Background/Aims: Accumulating evidence has highlighted the importance of long non-coding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in tumor biology. Among others, actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has been associated with non-small cell lung cancer (NSCLC). However, it remains unclear how AFAP1-AS1 participates in the development and progression of NSCLC. Methods: The peripheral blood samples were collected from patients with NSCLC. White blood cell subsets were classified and levels of interleukin (IL)-10, IL-12 and IFN-γ in serum were measured. We then identified its target gene of AFAP1-AS1 via bioinformatics methods. NSCLC cell line with the highest expression of AFAP1-AS1, i.e. H1975 was selected for in vitro experiments. A series of inhibitor, vector and siRNA were employed to validate the regulatory mechanisms of AFAP1-AS1 in the development and progression of NSCLC. Cell proliferation was detected by MTT assay and EdU staining. Cell migration and invasion, and cell cycle and apoptosis were measured by transwell assay and flow cytometry, respectively. Results: A high expression of AFAP1-AS1 was identified in NSCLC, alongside with a reduced level of IL-12 and increased levels of IL-10 and interferon (IFN)-γ. Aberrant expressions of AFAP1-AS1 were associated with pathological grade, TNM staging and metastatic potential of NSCLC. AFAP1-AS1 could activate interferon regulatory factor (IRF)7, the retinoid-inducible protein (RIG)-I-like receptor signaling pathway and Bcl-2 in vitro. Over-expression of AFAP1-AS1 promoted NSCLC cell proliferation, invasion and migration while inhibiting cell apoptosis. Conclusion: lncRNA AFAP1-AS1 promotes migration and invasion of non-small cell lung cancer via up-regulating IRF7 and the RIG-I-like receptor signaling pathway.

MicroRNA-221-3p promotes proliferation and invasion in non-small cell lung cancer via targeting Axin2 to regulate Wnt/β-catenin signaling pathway

2020 ◽  
Author(s):  
Jiangnan Zheng ◽  
Lingyun Dong ◽  
Xiaoyun Hu ◽  
Ying Xiao ◽  
Qiaozhen Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Proliferation And Invasion

Abstract ObjectiveThe mortality rate of lung cancer ranks first in malignant tumors. Among them, non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer patients. In this study, we explore part of the mechanism of development and progression of NSCLC.Methods/ ResultsFirstly, there was an increase in microRNA-221-3p (miR-221-3p) expression and a decrease in Axin2 expression in NSCLC tissues using real-time reverse transcription polymerase chain reaction. Further studies showed that miR-221-3p inhibited the expression of Axin2, which negatively regulated the Wnt signaling pathway. With the method of inhibiting and overexpressing the expression of miR-221-3p and/or Axin2 respectively in NSCLC cell lines A549 and H1975, we found that inhibiting the expression of miR-221-3p leaded to a decrease in cell proliferation, migration and invasion, just like the results of overexpressing Axin2. Relatively speaking, overexpression of miR-221-3P in NSCLC cell lines showed the increase of proliferation as well as the decrease of apoptosis. Thus, we knew that miR-221-3p promoted the migration and invasion of NSCLC cells in vitro. What’s more, according to western blot and EdU assay, we demonstrated that overexpression of miR-221-3p inhibited the expression of Axin2 and subsequently activate classical Wnt/β-catenin signaling pathway. At last, a series of methods were used to identify that miR-221-3p inhibited Axin2 expression, increased cell proliferation, invasion and migration, and decreased cell apoptosis.ConclusionOur results suggest that miR-221-3p inhibits the expression of Axin2 and indirectly activates the typical Wnt/β-catenin signaling pathway, thus promoting tumor proliferation and invasion in NSCLC.

scholarly journals Low miR-1231 expression predicts poor prognosis in non-small-cell lung cancer and accelerates cell proliferation, migration and invasion

2021 ◽  
Author(s):  
Lina Zhu ◽  
Ke Zhang ◽  
Chu Zhang ◽  
Hui Yu ◽  
Lirong Zhu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Biological Function ◽  
Prognostic Biomarker ◽  
Small Cell ◽  
Nsclc Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

Aim: miRNAs have been found to be involved in the tumor progression. This study aimed to assess the prognostic significance and biological function of miRNA-1231 (miR-1231) in non-small-cell lung cancer (NSCLC). Materials & methods: Expression of miR-1231 was measured by using quantitative real-time PCR. The prognosis value of miR-1231 was evaluated by Kaplan–Meier survival curves and Cox regression analysis. The biological function of miR-1231 was further studied. Results: Expression of miR-1231 in NSCLC patients and NSCLC cell lines were decreased. MiR-1231 was an independent prognostic biomarker. Overexpression of miR-1231 inhibited NSCLC cell proliferation, migration and invasion. Conclusion: Downregulated expression of miR-1231 serves as a prognostic biomarker of NSCLC and may be a potential therapeutic target.

scholarly journals Low miR-1231 expression predicts poor prognosis in non-small cell lung cancer and accelerates cell proliferation, migration and invasion

2020 ◽  
Author(s):  
Lina Zhu ◽  
Chu Zhang ◽  
Hui Yu ◽  
Lirong Zhu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Tumor Progression ◽  
Poor Prognosis ◽  
Biological Function ◽  
Small Cell ◽  
Nsclc Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract Background MicroRNAs (miRNAs) have been confirmed to be involved in the tumor progression of various cancer types. This study aimed to assess the prognostic significance and biological function of miR-1231 in patients with non-small cell lung cancer (NSCLC). Methods The expression of miR-1231 was estimated using quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognosis value of miR-1231 in patients with NSCLC. Cell experiments were performed to assess the biological function of miR-1231 in the tumor progression. Results In this study, we found that miR-1231 was an important tumor suppressor with significantly low expression in NSCLC tissues and cell lines compared with normal controls (all P < 0.001). MiR-1231 expression was significantly associated with tumor size (P = 0.037), lymph node metastasis (P = 0.001) and TNM stages (P = 0.001). Furthermore, the patients with low miR-1231 expression had shorter survival time than those with high miR-1231 expression (log-rank P = 0.010). In addition, miR-1231 was found to serve as an independent prognostic biomarker for the patients. The results of cell experiments indicated that miR-1231 downregulation could markedly promote NSCLC cell proliferation, migration and invasion, while miR-1231 overexpression could markedly inhibit NSCLC cell proliferation, migration and invasion. Conclusion All the data revealed that a downregulated expression of miR-1231 predicts the poor prognosis of NSCLC and promotes the tumor cell proliferation, migration and invasion. Therefore, we considered that miR-1231 may serve as a therapeutic target for NSCLC treatment.

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