POM121 promotes proliferation and metastasis in non-small-cell lung cancer through TGF-β/SMAD and PI3K/AKT pathways

2021 ◽  
pp. 1-10
Author(s):  
Lirong Guan ◽  
Lingli Zhang ◽  
Tengqi Wang ◽  
Lizhou Jia ◽  
Ning Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Biological Behavior ◽  
Migration And Invasion ◽  
Nuclear Pore ◽  
Tumor Diameter ◽  
Small Cell Lung ◽  
Functional Changes

BACKGROUND: Nuclear pore membrane protein 121 (POM121) is a novel biomarker involved in tumorigenesis and metastasis. However, little is known about the role of POM121 in non-small-cell lung cancer (NSCLC). OBJECTIVE: The aim of this study was to detect the expression of POM121 in NSCLC and its relationship with clinicopathologic feature and cell biological behavior, and explore the underlying mechanisms. METHODS: The expression of POM121 in NSCLC tissues and para-carcinoma tissues was compared by quantitative real-time PCR and immunohistochemistry analysis. The relationship between POM121 protein and clinicopathological characteristics in NSCLC was investigated. Roles of POM121 in NSCLC cells were investigated by CCK-8 assay, clone formation assay, transwell migration and invasion assay, and in vivo experiments. Variations of signaling pathways were determined by qRT-PCR and Western blot. RESULTS: The POM121 expression in NSCLC tissues was significantly higher than that in para-carcinoma tissues, both at the mRNA and protein level. The POM121 expression was related to sex, advanced differentiation, tumor diameter, lymph node metastases, distant metastases, American Joint Committee on Cancer (AJCC) stage, venous invasion, and perineural invasion in NSCLC. Kaplan-Meier analysis indicated that NSCLC patients with high POM121 expression had poor overall survival. Downregulation of POM121 inhibited cell proliferation, clone formation, migration and invasion. TGF-β/SMAD and PI3K/AKT pathways were involved in POM121-induced functional changes in NSCLC cells. CONCLUSION: POM121 plays an oncogenic role in NSCLC through TGF-β/SMAD and PI3K/AKT pathways. POM121 expression is a potential independent prognostic factor for NSCLC.

scholarly journals Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xingyun Liu ◽  
Jia Yang ◽  
Chengwei Yang ◽  
Xiang Huang ◽  
Mingming Han ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Biological Behavior ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
H460 Cells

Abstract Background Morphine, a µ-opioid receptor (MOR) agonist, has been shown to be related to the activity of cancer cells, and a higher morphine dosage reduces the survival time of patients with lung cancer. However, the effect of morphine on the malignant behavior of lung cancer cells remains unclear. The aim of this study was to investigate the specific molecular mechanism by which morphine regulates the malignant biological behavior of non-small cell lung cancer. Methods Immunofluorescence staining and Western blot analyses were performed to detect MOR expression. H460 non-small cell lung cancer cells were used in this study, and cell proliferation, the cell cycle and apoptosis were evaluated using Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Cell migration and invasion were detected using wound healing and Transwell assays. The effect of morphine on lung cancer development in vivo was examined by performing a xenograft tumor assay following morphine treatment. Results Morphine promoted the growth of H460 cells both in vivo and in vitro. Morphine enhanced cell migration and invasion, modified cell cycle progression through the S/G2 transition and exerted an antiapoptotic effect on H460 cells. Additionally, morphine increased Rous sarcoma oncogene cellular homolog (Src) phosphorylation and activated the phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Treatment with the MOR antagonist methylnaltrexone (MNTX) and the Src inhibitor protein phosphatase 1 (PP1) reduced the phosphorylation induced by morphine. Furthermore, MNTX, PP1, and the PI3K/AKT inhibitor deguelin reversed the antiapoptotic effect of morphine on lung cancer cells. Conclusion Morphine promotes the malignant biological behavior of H460 cells by activating the MOR and Src/mTOR signaling pathways.

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 Silibinin Regulates Tumor Progression and Tumorsphere Formation by Suppressing PD-L1 Expression in Non-Small Cell Lung Cancer (NSCLC) Cells

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1632
Author(s):  
Alexis Rugamba ◽  
Dong Young Kang ◽  
Nipin Sp ◽  
Eun Seong Jo ◽  
Jin-Moo Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Small Cell Lung Cancer ◽  
Anticancer Activity ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Molecular Signaling ◽  
Small Cell Lung

Recently, natural compounds have been used globally for cancer treatment studies. Silibinin is a natural compound extracted from Silybum marianum (milk thistle), which has been suggested as an anticancer drug through various studies. Studies on its activity in various cancers are undergoing. This study demonstrated the molecular signaling behind the anticancer activity of silibinin in non-small cell lung cancer (NSCLC). Quantitative real-time polymerase chain reaction and Western blotting analysis were performed for molecular signaling analysis. Wound healing assay, invasion assay, and in vitro angiogenesis were performed for the anticancer activity of silibinin. The results indicated that silibinin inhibited A549, H292, and H460 cell proliferation in a concentration-dependent manner, as confirmed by the induction of G0/G1 cell cycle arrest and apoptosis and the inhibition of tumor angiogenesis, migration, and invasion. This study also assessed the role of silibinin in suppressing tumorsphere formation using the tumorsphere formation assay. By binding to the epidermal growth factor receptor (EGFR), silibinin downregulated phosphorylated EGFR expression, which then inhibited its downstream targets, the JAK2/STAT5 and PI3K/AKT pathways, and thereby reduced matrix metalloproteinase, PD-L1, and vascular endothelial growth factor expression. Binding analysis demonstrated that STAT5 binds to the PD-L1 promoter region in the nucleus and silibinin inhibited the STAT5/PD-L1 complex. Altogether, silibinin could be considered as a candidate for tumor immunotherapy and cancer stem cell-targeted therapy.

scholarly journals Over-Expression of LSD1 Promotes Proliferation, Migration and Invasion in Non-Small Cell Lung Cancer

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e35065 ◽  
Author(s):  
Tangfeng Lv ◽  
Dongmei Yuan ◽  
Xiaohui Miao ◽  
Yanling Lv ◽  
Ping Zhan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Over Expression

scholarly journals Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer

2020 ◽  
Author(s):  
Zhi-Gang Sun ◽  
Feng Pan ◽  
Jing-Bo Shao ◽  
Qian-Qian Yan ◽  
Lu Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Nude Mice ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Kinesin Superfamily

Abstract Background: Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cell lung cancer (NSCLC). Methods: KIF21B expression in 72 cases of NSCLC tissues was measured by immunohistochemical staining (IHC). We used shRNA-KIF21B interference to silence KIF21B in NSCLC H1299 and A549 cells and normal lung epithelial bronchus BEAS-2B cells. The biological roles of KIF21B in the growth and metastasis abilities of NSCLC cells were measured by Cell Counting Kit-8 (CCK8), colony formation and Hoechst 33342/PI, wound-healing, and Transwell assays, respectively. Expression of apoptosis-related proteins was determined using western blot. The effect of KIF21B on tumor growth in vivo was examined using nude mice model. Results: KIF21B was up-regulated in NSCLC tissues, and correlated with pathological lymph node and pTNM stage, its high expression was predicted a poor prognosis of patients with NSCLC. Silencing of KIF21B mediated by lentivirus-delivered shRNA significantly inhibited the proliferation ability of H1299 and A549 cells. KIF21B knockdown increased apoptosis in H1299 and A549 cells, down-regulated the expression of Bcl-2 and up-regulated the expression of Bax and active Caspase 3. Moreover, KIF21B knockdown decreased the level of phosphorylated form of Akt (p-Akt) and Cyclin D1 expression in H1299 and A549 cells. In addition, silencing of KIF21B impeded the migration and invasion of H1299 and A549 cells. Further, silencing of KIF 21B dramatically inhibited xenograft growth in BALB/c nude mice. However, silencing of KIF21B did not affect the proliferation, migration and invasion of BEAS-2B cells.Conclusions: These results reveal that KIF21B is up-regulated in NSCLC and acts as an oncogene in the growth and metastasis of NSCLC, which may function as a potential therapeutic target and a prognostic biomarker for NSCLC.

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