scholarly journals MiR-106b-5p Promotes Proliferation and Inhibits Apoptosis by Regulating BTG3 in Non-Small Cell Lung Cancer

2017 ◽  
Vol 44 (4) ◽  
pp. 1545-1558 ◽  
Author(s):  
Ke Wei ◽  
Chunfeng Pan ◽  
Guoliang Yao ◽  
Bin Liu ◽  
Teng Ma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Luciferase Assay ◽  
Small Cell Lung

Background/Aims: MicroRNAs have been validated to play a crucial role in tumorigenesis of non-small cell lung cancer (NSCLC). Although miR-106b-5p has been reported to play a vital role in various malignancies the physiological function of miR-106b-5p in NSCLC still remain unknown. In this study, we investigated the role of miR-106b-5p in NSCLC. Methods: Quantitative real-time polymerase chain reaction was conducted to estimate the expression of miR-106b-5p and BTG3 in both NSCLC tissues and cell lines. The effects of miR-106b-5p on proliferation were determined in vitro using CCK-8 proliferation assays, 5-ethynyl-2’-deoxyuridine (EdU) incorporation, colony formation assays and cell-cycle assays and the in vivo effects were evaluated by a mouse tumorigenicity model. Cell apoptosis and cell cycle was investigated by flow cytometric analysis in vitro. The molecular mechanism underlying the relevance between miR-106b-5p and BTG3 was confirmed by luciferase assay and western blot. Results: In current study, we found a relatively higher miR-106b-5p and lower BTG3 expression in NSCLC specimens and cell lines. BTG3 was verified as a direct target of miR-106b-5p by luciferase assay. In vitro, over-expression of miR-106b-5p promoted proliferation and inhibited apoptosis by down-regulating BTG3 expression. In vivo, miR-106b-5p promoted xenograft tumor formation. Conclusion: Our findings revealed for the first time that miR-106b-5p plays a tumorigenesis role in NSCLC progression by down-regulating BTG3 expression, which may lead to a novel insight to the potential biomarker and novel therapeutic strategies for NSCLC patients.

Expression of CD133, a possible marker for cancer stem cells (CSCs), in small cell lung cancer (SCLC) cell lines and non- small cell lung cancer (NSCLC) cell lines

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22100-e22100
Author(s):  
T. Hayashi ◽  
H. Tao ◽  
M. Jida ◽  
T. Kubo ◽  
H. Yamamoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Lung Cancers

e22100 Background: Cancer stem cell (CSCs) are believed to play important roles in tumor development, recurrence or metastasis. Identification of CSCs may have a therapeutic significance. CD133 expression has been shown on a minority of various human cancer cells with high capability of self-renewal and proliferation. Therefore, CD133 is thought to be one of possible markers for CSCs. Regarding human lung cancers, the existence, prevalence or roles of CD133 positive cells has not been fully understood. Methods: We examined CD133 mRNA by quantitative real-time PCR and sorted CD133-positive cells by fluorescence-activated cell sorting (FACS) using human small cell lung cancer(SCLC) and non-small cell lung cancer (NSCLC) cell lines. We evaluated differences of cell proliferation between CD133-positive and -negative cells by MTS assay in vitro and by subcutaneous injection for non- obese diabetic/severe combined immunodeficiency (NOD/SCID) mice in vivo. Results: CD133 expression was almost restricted in SCLC cell lines. CD133 mRNA expression or CD133-positive cell population was scarcely observed in NSCLC cell lines. In two SCLC cell lines examined (NCI-H82 and NCI-H69), CD133 positive cells had higher tumorgenicity both in vivo and in vitro than NSCLC cell lines. Conclusions: The expression status of CD133 is totally different between NSCLCs and SCLCs, probably reflecting the difference of these progenitor cells. Our results indicate that CD133-positive cells in SCLC cell are responsible for tumor growth. However, in view of their wide prevalence, CD133-positive cells do not seem to be a candidate for CSCs, at least in cell lines. To investigate the molecular and functional characteristics of CD133-positive cells may lead to a new therapeutic strategy for human lung cancers, especially for SCLCs. No significant financial relationships to disclose.

scholarly journals MiR-142-5p Suppresses Tumorigenesis by Targeting PIK3CA in Non-Small Cell Lung Cancer

2017 ◽  
Vol 43 (6) ◽  
pp. 2505-2515 ◽  
Author(s):  
Zhao Wang ◽  
Zhimin Liu ◽  
Xiaojie Fang ◽  
Han Yang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Cancer Growth ◽  
Cancer Tissue ◽  
Small Cell Lung

Background/Aims: Numerous studies have demonstrated that aberrant microRNA (miRNA) expression is involved in human disease including cancer. To date, the potential miRNAs regulating lung cancer growth and progression are not fully identified yet. Methods: In this study, the expression of miR-142-5p was measured in non-small cell lung cancer tissue and cell lines by qRT-PCR. The functional assays including the cell viability, colony formation, cell migration and invasion were performed in miR-142-5p mimic or inhibitor transfected cell lines (in vitro) and the cell tumorigenesis in nude mice (in vivo). The fluorescence ratios of cell viability were recorded using a multi-plate reader (Synergy 2, BioTek, Winooski, VT, USA) and the colonies were counted using an ELIspot Bioreader 5000 (BIO-SYS, Karben, GE). Results: MiR-142-5p was significantly downregulated in non-small cell lung cancer tissue and cell lines compared to normal human lung tissues. Overexpression of miR-142-5p resulted in decreased expression of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) at both mRNA and protein levels. We found that miR-142-5p overexpression markedly suppressed cell proliferation in vitro and in vivo. Conversely, inhibition of miR-142-5p promoted lung cancer growth. Mechanistic studies showed that PIK3CA was a potential target of miR-142-5p and it mediated reduction of PIK3CA resulting in suppression of PI3K/Akt pathway. Conclusions: Our results demonstrate that miR-142-5p functions as a growth suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA in non-small cell lung cancer.

scholarly journals (−)-Epigallocatechin-3-gallate derivatives combined with cisplatin exhibit synergistic inhibitory effects on non-small-cell lung cancer cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jing Wang ◽  
Peiyuan Sun ◽  
Qi Wang ◽  
Pan Zhang ◽  
Yuna Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Signaling ◽  
Small Cell Lung ◽  
Egfr Signaling Pathway

Abstract Background Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The inhibition of epidermal growth factor receptor (EGFR) signaling by tyrosine kinase inhibitors or monoclonal antibodies plays a key role in NSCLC treatment. Unfortunately, these treatment strategies are limited by eventual resistance and cell lines with differential EGFR status. Therefore, new therapeutic strategies for NSCLC are urgently required. Methods To improve the stability and absorption of (−)-epigallocatechin-3-gallate (EGCG), we synthesized a series of EGCG derivatives. The antitumor activities of EGCG derivatives with or without cisplatin were investigated in vitro and vivo. Cell proliferation, cell cycle distribution and apoptosis were measured in NSCLC cell lines and in vivo in a NCI-H441 xenograft model. Results We found that the EGCG derivatives inhibited cell viability and colony formation, caused cell cycle redistribution, and induced apoptosis. More importantly, the combination of the EGCG derivative and cisplatin led to increased growth inhibition, caused cell cycle redistribution, and enhanced the apoptosis rate compared to either compound alone. Consistent with the experiments in vitro, EGCG derivatives plus cisplatin significantly reduced tumor growth. Conclusions The combination treatment was found to inhibit the EGFR signaling pathway and decrease the expression of p-EGFR, p-AKT, and p-ERK in vitro and vivo. Our results suggest that compound 3 is a novel potential compound for NSCLC patients.

scholarly journals Development of paclitaxel loaded pegylated gelatin targeted nanoparticles for improved treatment efficacy in non-small cell lung cancer (NSCLC): an in vitro and in vivo evaluation study

2021 ◽  
Author(s):  
Minwei Gu ◽  
Jun Luan ◽  
Kun Song ◽  
Cao Qiu ◽  
XiaoLi Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Targeted Nanoparticles ◽  
Pulmonary Deposition

Purpose: To develop and evaluate paclitaxel (PTX) loaded pegylated gelatin targeted nanoparticles for improved efficacy in non-small cell lung cancer (NSCLC) treatment. Method: PTX loaded gelatin nanoparticles (PTX-GNP) were prepared by crosslinking with glutaraldehyde aqueous solution. These nanoparticles (NPs) were further incubated with PEG 400 to form PEGylated NPs (PEG-PTX-GNP). The NPs were evaluated for surface morphology, size, zeta potential, encapsulation efficiency, drug loading, in vitro drug release, cytotoxicity in an assay on cancer cell lines L132, in vitro cellular uptake in an assay in L132 and 293T cell lines, in vivo antitumor activity on female Balb/c mice, pulmonary deposition, histopathology, and immunohistochemical properties. Results: The nanoparticles were of spherical shape with smooth surface characteristics. The observed DL was of 20.18 to 32.11%, as particle size was of 90 to 115 nm. Zeta potential and polydispersity index (PDI) were within acceptable ranges. Encapsulation was effective when the NPs had a size of 80.50 nm to 98.12 nm. The PEGylated PTX loaded nanoparticles (PEG-PTX-GNP, GNP4) showed similar PTX release profile to that of the NP4 formulation. PEGylated NPs showed the desired PTX release pattern that is required for cancer treatment. In an in vitro cytotoxicity study, PEG-PTX-GNP showed the maximum antiproliferative activity over the period of 24 hours, followed by PTX-GNP, pure PTX and BPEG-GNP. PEG-PTX-GNP showed the highest internalization within both cell lines, followed by PTX-GNP and pure PTX. The survival rate of animals in PEG-PTX-GNP group was 100%, proving the safety and efficacy of the treatment. PEG-PTX-GNP showed the highest antitumor activity as compared to other formulations. The pulmonary deposition rate was the highest (6.5 to 12.55 μg/g) in PEG-PTX-GNP formulations. Histopathology and immunohistochemical study proved that PEG-PTX-GNP had greater anticancer potential than other tested formulations. Conclusion: This study confirms the potential use of paclitaxel loaded PEGylated gelatin targeted nanoparticles for improved efficacy in non-small cell lung cancer (NSCLC) treatment.

scholarly journals LncRNA SNHG19 Promotes the Development of Non-Small Cell Lung Cancer via Mediating miR-137/E2F7 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Guang-Yin Zhao ◽  
Zhao-Feng Ning ◽  
Rui Wang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Cancer Tissues

ObjectiveNon-small cell lung cancer (NSCLC) is a common malignant tumor, which has high incidence and low the 5-year survival rate. Long non-coding RNAs (lncRNAs) play critical roles in carcinoma occurrence and metastasis. Herein, our aim was to investigate the effects of lncRNA SNHG19 in NSCLC progression.Materials and MethodsLong non-coding RNA Small Nucleolar RNA Host Gene 19 (lncRNA SNHG19) expression level was measured by bioinformatics and qRT-PCR. Edu, Transwell, and scratch assays were performed to explore the role of si-SNHG19 or SNHG19 on NSCLC progression. Luciferase assay was used to verify the relationship between SNHG19/E2F7 and miR-137. The experiment of Xenograft was used for exploring the function of SNHG19 in vivo.ResultsSNHG19 was upregulated in cancer tissues, patients plasma and cell lines of NSCLC. Knockdown of SNHG19 inhibited cell proliferation, migration, and invasion. Luciferase assay confirmed that SNHG19 regulated E2F7 expression via interacting with miR-137. Overexpression of SNHG19 accelerated NSCLC tumor progression via miR-137/E2F7 axis both in vitro and in vivo.ConclusionsOur results clarified the SNHG19 function for the first time, and SNHG19 promoted the progression of NSCLC, which was mediated by the miR-137/E2F7 axis. This study might provide new understanding and targets for NSCLC diagnosis and treatment.

scholarly journals Clinically Relevant Chemotherapeutics Have the Ability to Induce Immunogenic Cell Death in Non-Small Cell Lung Cancer

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1474 ◽  
Author(s):  
Tal Flieswasser ◽  
Jinthe Van Loenhout ◽  
Laurie Freire Boullosa ◽  
Astrid Van den Eynde ◽  
Jorrit De Waele ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Immunogenic Cell Death ◽  
Small Cell Lung

The concept of immunogenic cell death (ICD) has emerged as a cornerstone of therapy-induced anti-tumor immunity. To this end, the following chemotherapies were evaluated for their ability to induce ICD in non-small cell lung cancer (NSCLC) cell lines: docetaxel, carboplatin, cisplatin, oxaliplatin and mafosfamide. The ICD hallmarks ATP, ecto-calreticulin, HMGB1, phagocytosis and maturation status of dendritic cells (DCs) were assessed in vitro. Furthermore, an in vivo vaccination assay on C57BL/6J mice was performed to validate our in vitro results. Docetaxel and the combination of docetaxel with carboplatin or cisplatin demonstrated the highest levels of ATP, ecto-calreticulin and HMGB1 in three out of four NSCLC cell lines. In addition, these regimens resulted in phagocytosis of treated NSCLC cells and maturation of DCs. Along similar lines, all mice vaccinated with NSCLC cells treated with docetaxel and cisplatin remained tumor-free after challenge. However, this was not the case for docetaxel, despite its induction of the ICD-related molecules in vitro, as it failed to reject tumor growth at the challenge site in 60% of the mice. Moreover, our in vitro and in vivo data show the inability of oxaliplatin to induce ICD in NSCLC cells. Overall with this study we demonstrate that clinically relevant chemotherapeutic regimens in NSCLC patients have the ability to induce ICD.

scholarly journals Exosomal miR-141 promotes tumor angiogenesis via KLF12 in small cell lung cancer

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Shuangshuang Mao ◽  
Zhiliang Lu ◽  
Sufei Zheng ◽  
Hao Zhang ◽  
Guochao Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Target Gene ◽  
Tube Formation ◽  
Small Cell ◽  
Luciferase Assay ◽  
Small Cell Lung

Abstract Background Angiogenesis, a basic requirement for tumor cell survival, is considered to be a malignant characteristic of small cell lung cancer (SCLC) and is closely related to the poor outcomes of SCLC patients. miR-141 has been found to play pro- and antiangiogenic roles in different cancers, but its role in SCLC angiogenesis has never been explored. Methods Total RNA was isolated from plasm exosomes and serum of SCLC patients to examine the expression of miR-141 by qRT-PCR. Cell proliferation, invasion, migration, tube formation assay, aortic ring assay and mouse tumor model were used to investigate the effect of exosomal miR-141 in angiogenesis in vitro and in vivo. Dual-luciferase assay was conducted to explore the target gene of miR-141. Results Circulating miR-141 was upregulated in samples from 122 SCLC patients compared with those from normal volunteers and that the increase in miR-141 was significantly associated with advanced TNM stages, implying the potential oncogenic role of miR-141 in SCLC malignancy. In vitro, miR-141 that was packaged into SCLC cell-secreted exosomes and delivered to human umbilical vein vascular endothelial cells (HUVECs) via exosomes facilitated HUVEC proliferation, invasion, migration and tube formation and promoted microvessel sprouting from mouse aortic rings. Matrigel plug assays demonstrated that SCLC cell-derived exosomal miR-141 induced neoangiogenesis in vivo. Furthermore, mouse subcutaneous tumor nodules that were developed from miR-141-overexpressing SCLC cells had a higher microvessel density (MVD) and grew faster than those developed from negative control cells. KLF12 was found to be the direct target gene of miR-141 and that the proangiogenic effect of miR-141 on HUVECs was abrogated by KLF12 overexpression. Conclusions Our results demonstrate the specific function of the exosomal miR-141/KLF12 pathway in SCLC angiogenesis for the first time and provide potential novel targets for antiangiogenic therapies for SCLC patients.

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