scholarly journals Zebrafish xenograft model of human lung cancer for studying the function of LINC00152 in cell proliferation and invasion

2020 ◽  
Author(s):  
Wenyi Shen ◽  
Juan Pu ◽  
Jing Sun ◽  
Bing Tan ◽  
Wei Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Cultured Cells ◽  
Human Cancer ◽  
Noncoding Rnas ◽  
Xenograft Model ◽  
Long Noncoding Rnas ◽  
Proliferation And Invasion

Abstract Background: Numerous studies have shown that long noncoding RNAs play important roles in human cancer progression. Although zebrafish xenografts have recently become a novel in vivo model for human cancer research, whether such models can be used to study the function of long noncoding RNAs remains unknown. Methods: In vitro studies validated the roles of LINC00152 in the proliferation and invasion of lung cancer cells. In vivo studies of zebrafish xenografts also confirmed these roles of LINC00152. In vivo confocal imaging was used to more accurately evaluate the function of LINC00152 in cell proliferation and migration. Pharmacological experiments were further performed to study the potential ability of LINC00152 downregulation combined with an EGFR inhibitor to treat tumors in cultured cells and the zebrafish xenograft model. Results: Silencing of LINC00152 suppressed cell proliferation and invasion in SPCA1 and A549 lung cancer cell lines in vitro . In the zebrafish xenograft model, knockdown of LINC00152 reduced the proliferation and migration of lung cancer cells, as indicated by the two imaging methods at different magnifications. Moreover, the knockdown of LINC00152 enhanced the inhibition effect of afatinib for lung cancer progression in cultured cells and the zebrafish xenograft model. Conclusion: Our study reveals the oncogenic roles and potential for LINC00152 to be a target for tumor treatment in lung cancer using zebrafish xenograft models, and the findings suggest that this model could be used for functional and application studies of human long noncoding RNAs in tumor biology.

scholarly journals Zebrafish xenograft model of human lung cancer for studying the function of LINC00152 in cell proliferation and invasion

2020 ◽  
Author(s):  
Wenyi Shen ◽  
Juan Pu ◽  
Jing Sun ◽  
Bing Tan ◽  
Wei Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cultured Cells ◽  
Human Cancer ◽  
Xenograft Model ◽  
Lung Cancer Cells ◽  
Proliferation And Invasion

Abstract Background: Numerous studies show that long non-coding RNAs take important roles in human cancer progression. Although zebrafish xenograft become a novel in vivo model for human cancer research recently, whether it can be used for studying the function of lncRNAs remains unknown.Methods: In vitro studies validated the roles of LINC00152 in the proliferation and invasion of lung cancer cells. In vivo studies by using zebrafish xenograft also confirmed these roles of LINC00152. In vivo confocal imaging was also used to evaluate the function of LINC00152 in cell proliferation and migration more accurately. Pharmacology experiments were further performed to study the potential tumor treatment of LINC00152 downregulation combined with EGFR inhibitor in cultured cells and zebrafish xenograft.Results: Silencing of LINC00152 suppressed cell proliferation and invasion in SPCA1 and A549 lung cancer cell lines in vitro . In zebrafish xenograft model, knockdown of LINC00152 reduced the proliferation and migration of lung cancer cells by two imaging methods at different magnification. Moreover, knocking-down LINC00152 enhanced the inhibition effect of afatinib for lung cancer progression in cultured cells and zebrafish xenograft model.Conclusion: Our study reveals the oncogenic roles and potential tumor treatment target of LINC00152 in lung cancer cells by zebrafish xenograft models, suggesting that this model could be used for the functional and application study of human lncRNA in tumor biology.* Wenyi Shen and Juan Pu contributed equally to this work.

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 The Role of Cavin3 in the Progression of Lung Cancer and Its Mechanism

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Gaozhong Sun ◽  
Kewei Ni
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Tumor Formation ◽  
Migration And Invasion ◽  
Clinical Value ◽  
Promote Cell Proliferation ◽  
Cancer Tissues

Objective. The purpose of this study was to describe the role of Cavin3 in the progression of lung cancer and its underlying mechanism. Methods. Totally, 200 cases of lung cancer tissues and corresponding paracancer tissues were collected. Cavin3 expression in samples was determined by qRT-PCR, and the correlation with lung cancer stages as well as prognosis was statistically analyzed combined with matched clinical information. To investigate the mechanism of Cavin3 in lung cancer progression, firstly, Cavin3 was detected in lung cancer cell lines A549, PC9, and H520. Then, cells with stable Cavin3 overexpression and Cavin3 knockout were established to determine the effect of Cavin3 overexpression on the mammalian target of rapamycin (mTOR) signaling pathway. Subsequently, cells were harvested for cell proliferation, migration, and invasion assays in vitro, as well as nude mouse transplantation tumor experiment in vivo. Results. Cavin3 was seen to be highly expressed in cancer tissues. Statistical analysis with matched clinical data showed that Cavin3 as a prognostic indicator of lung cancer had important clinical value. In addition, it could be found that high expression of Cavin3 was able to promote cell proliferation, migration, and invasion and also potentiate tumor formation in vivo. Conclusion. Cavin3 was highly expressed in lung cancer, and it was capable to promote cell proliferation, invasion, and migration.

scholarly journals TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ke Ren ◽  
Jinghui Sun ◽  
Lingling Liu ◽  
Yuping Yang ◽  
Honghui Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Qrt Pcr ◽  
Proliferation And Invasion

Non-small cell lung cancer (NSCLC) is the main type of lung cancer with high mortality worldwide. To improve NSCLC therapy, the exploration of molecular mechanisms involved in NSCLC progression and identification of their potential therapy targeting is important. Long noncoding RNAs (lncRNAs) have shown important roles in regulating various tumors progression, including NSCLC. We found lncRNA GHRLOS was decreased in NSCLC cell lines and tissues which correlated with poor prognosis of NSCLC patients. However, the role and underlying mechanisms of lncRNA GHRLOS in NSCLC progression remains elusive. The expression of lncRNA GHRLOS was examined in NSCLC cell lines and biopsy specimens of patients with NSCLC by quantitative real time polymerase chain reaction (qRT-PCR). The effects of GHRLOS on proliferation, invasion and apoptosis of NSCLC cells were determined by both in vitro and in vivo experiments. The interaction between GHRLOS and TP53 was determined by dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) combined with qRT-PCR analysis. RNA immunoprecipitation (RIP) was conducted to validate the binding between GHRLOS and microRNA-346 (miR-346). Dual-luciferase reporter assays were also carried out to reveal the interaction between miR-346 and the 3’ untranslated region (3’UTR) of adenomatous polyposis coli (APC) mRNA.Our data demonstrated that overexpression of lncRNA GHRLOS suppressed cancer cell proliferation and invasion as well as promoted cell apoptosis by regulating the expression of CDK2, PCNA, E-cadherin, N-cadherin, Bax, and Bcl-2 in NSCLC cells. Moreover, lncRNA GHRLOS was upregulated by the binding of TP53 to the GHRLOS promoter. The binding target of lncRNA GHRLOS was identified to be miR-346. Impressively, overexpression of miR-346 promoted cell proliferation and invasion, as well as inhibited cell apoptosis, however, these effects can be blocked by overexpression of lncRNA GHRLOS both in vitro and in vivo. In summary, this study reveals lncRNA GHRLOS, upregulated by TP53, acts as a molecule sponge of miR-346 to cooperatively modulates expression of APC, a miR-346 target, and potentially inhibits NSCLC progression via TP53/lncRNA GHRLOS/miR-346/APC axis, which represents a novel pathway that could be useful in targeted therapy against NSCLC.

scholarly journals SNX20AR/MiRNA-301a-3p/SNX20 Axis Associated With Cell Proliferation and Immune Infiltration in Lung Adenocarcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Yixiao Yuan ◽  
Xiulin Jiang ◽  
Lin Tang ◽  
Juan Wang ◽  
Qianqian Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
Immune Cell ◽  
Human Cancer ◽  
Dna Hypermethylation ◽  
Over Expression ◽  
Immune Infiltration ◽  
And Migration

Lung cancer is the most common tumor with severe morbidity and high mortality. Increasing evidence has demonstrated that SNX20 plays crucial roles in the progression of human cancer. However, the functions and mechanism of SNX20 in LUAD are still barely known. Here, we employ the TCGA, GEO and CCLE databases to examine the expression of SNX20 in human varies cancer, the results shown that SNX20 is down-regulated in lung Adenocarcinoma, SNX20 level was significantly positive correlated with poor prognosis and lung cancer immune cell infiltration. We found that over-expression of SNX20 significantly restrain NSCLC cell proliferation and migration. Subsequently, we discover a network regulating SNX20 in LUAD, further study found that the decreased of the SNX20 likely caused by DNA hypermethylation. Furthermore, we identified that SNX20AR/miRNA-301a-3p mediated decreased of SNX20 correlated with lung cancer progression and cancer immune infiltration in LUAD. Our findings suggested that ncRNAs play a crucial role in the regulatory network of SNX20. Collectively, our findings demonstrate the suppressor roles of the SNX20AR/miRNA-301a-3p/SNX20 axis in Lung Adenocarcinoma, represent that SNX20 have the potential of as an effective therapeutic target in future.

scholarly journals LncRNA DLEU1 Contributes to the Growth and Invasion of Colorectal Cancer via Targeting miR-320b/PRPS1

2021 ◽  
Vol 11 ◽  
Author(s):  
Dong Xu ◽  
Fei Yang ◽  
Yongchao Fan ◽  
Wanling Jing ◽  
Jianfei Wen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Human Cancer ◽  
Xenograft Model ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Phosphoribosyl Pyrophosphate ◽  
Novel Target

Growing evidences suggest that long non-coding RNAs (lncRNAs) are closely correlated to the development of human cancer, such as colorectal cancer (CRC). A previous report suggested that DLEU1 accelerated CRC development. However, DLEU1’s underlying mechanism in CRC remains unclear. In our study, the level of DLEU1 in CRC tissues is investigated by qRT-PCR. Our data exhibited that DLEU1 level was observably increased in CRC tissues and CRC cell lines and was closely associated with bad prognosis of CRC patients. CRC cell proliferation was repressed by sh-LncRNA DLEU1, whereas cell apoptosis was markedly stimulated. Moreover, knockdown of DLEU1 inhibited cell migration and invasion. Mechanistically, through interacting with miR-320b in CRC, DLEU1 promoted the level of PRPS1 which was a target of miR-320b. The rescue experiment confirmed that knockdown of DLEU1 repressed cell proliferation, migration and invasion while stimulated cell apoptosis via miR-320b/phosphoribosyl pyrophosphate synthetase 1 (PRPS1) axis. Meanwhile, the data of xenograft model exhibited that inhibition of DLEU1 suppressed tumor growth in vivo. In summary, DLEU1 knockdown may repress PRPS1 expression via miR-320b, and then repress cell proliferation, migration and invasion while stimulate cell apoptosis. Our research may provide a novel target for the treatment of CRC.

scholarly journals Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 49 ◽  
Author(s):  
Young Yun Jung ◽  
Muthu K. Shanmugam ◽  
Acharan S. Narula ◽  
Chulwon Kim ◽  
Jong Hyun Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Mouse Model ◽  
A549 Cells ◽  
Xenograft Model ◽  
Signaling Cascade ◽  
Anticancer Effects ◽  
Anti Cancer

Oxymatrine (OMT) is a major alkaloid found in radix Sophorae flavescentis extract and has been reported to exhibit various pharmacological activities. We elucidated the detailed molecular mechanism(s) underlying the therapeutic actions of OMT in non-small cell lung cancer (NSCLC) cells and a xenograft mouse model. Because the STAT5 signaling cascade has a significant role in regulating cell proliferation and survival in tumor cells, we hypothesized that OMT may disrupt this signaling cascade to exert its anticancer effects. We found that OMT can inhibit the constitutive activation of STAT5 by suppressing the activation of JAK1/2 and c-Src, nuclear localization, as well as STAT5 binding to DNA in A549 cells and abrogated IL-6-induced STAT5 phosphorylation in H1299 cells. We also report that a sub-optimal concentration of OMT when used in combination with a low dose of paclitaxel produced significant anti-cancer effects by inhibiting cell proliferation and causing substantial apoptosis. In a preclinical lung cancer mouse model, OMT when used in combination with paclitaxel produced a significant reduction in tumor volume. These results suggest that OMT in combination with paclitaxel can cause an attenuation of lung cancer growth both in vitro and in vivo.

scholarly journals Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Lili Mi ◽  
Lianhui Lei ◽  
Xiaolei Yin ◽  
Ning Li ◽  
Jianfei Shi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Colony Formation ◽  
Human Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
The Impact

Abstract Background: Gastric cancer (GC) remains one of the most common malignancies worldwide. Increasing evidence has demonstrated that circRNAs serve as critical roles in human cancer, including GC. In the present study, we focused on the detailed function and mechanism of circ_0000144 on GC progression. Methods: The levels of circ_0000144, miR-623 and G-protein-coupled receptor, family C, group 5, member A (GPRC5A) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Targeted relationships among circ_0000144, miR-623 and GPRC5A were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, colony formation, apoptosis, migration and invasion were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry and transwell assays. Measurement of glutamine and α-ketoglutarate (α-KG) levels was performed using a corresponding assay kit. GPRC5A protein expression was detected using Western blot. In vivo assays were used to explore the impact of circ_0000144 on tumor growth. Results: Our data indicated that circ_0000144 was up-regulated and miR-623 was down-regulated in GC tissues and cells. Circ_0000144 interacted with miR-623 through directly binding to miR-623. Moreover, the knockdown of circ_0000144 weakened GC cell proliferation, colony formation, migration, invasion and glutaminolysis and accelerated cell apoptosis by up-regulating miR-623. GPRC5A was a direct target of miR-623 and circ_0000144 protected against GPRC5A repression through sponging miR-623. Furthermore, miR-623-mediated regulation on GC cell progression was reversed by the stored expression of GPRC5A. Additionally, circ_0000144 depletion inhibited tumor growth in vivo. Conclusion: Our study indicated that circ-0000144 knockdown repressed GC progression at least partly by regulating GPRC5A expression via sponging miR-623, illumining a novel therapeutic target for GC treatment.

scholarly journals MUC3A Promotes Non-Small Cell Lung Cancer Progress via Activating NFκB Pathway and Attenuates Radiosensitivity

2020 ◽  
Author(s):  
Yingming Sun ◽  
Xiaoge Sun ◽  
Chengcheng You ◽  
Shijing Ma ◽  
Yuan Luo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Clinical Outcomes ◽  
Nuclear Translocation ◽  
Xenograft Model ◽  
High Expression ◽  
G1 Arrest ◽  
Nfκb Pathway

Abstract Background: MUC3A is highly expressed in lung adenocarcinoma, but its functions and effects on clinical outcomes are not well understood.Methods: Tissue microarray was used to analysis the relathionship between MUC3A and clinicalpathological charcristics of lung adenocarcinoma; Colony formation and MTT array ware used to detect cell proliferation; WB applied to investigate the protein amount; Transwell was applied to evaluate cell invasion; IF was used to observe the location and expression of targeted proteins; IP was use to prove the binding of proteins. Mcherry-GFP-LC3 II adenovirus and TEM were performed to observe cell autophagy. Xnograft mouse model were used to investigate the effect of MUC3A in vivo.Result: 92 patients’ tumor samples indicated that high expression of MUC3A was associated with poor prognosis, advanced staging, and low differentiation. Co-immunoprecipitation results revealed that MUC3A interacted with RELA. MUC3A activated the NFκB pathway via promoting RELA phosphorylation and interfering the binding of RELA to IκB. MUC3A knockdown significantly suppressed cell proliferation and induced G1 arrest. MUC3A deficiency increased radiation-induced DNA double strain breaks via impairing the BRCA-1/RAD51 pathway and nuclear translocation of P53 and XCRR6. Moreover, MUC3A deficiency induced autophagy in lung cancer cells. MUC3A knockdown significantly suppressed tumor growth in xenograft model and had a synergistic effect with radiation. Less nuclear translocation of RELA and P53 was also observed in tumor tissue in vivo.Conclusion: MUC3A was a potential oncogene, and its high expression was associated with unfavorable clinical outcomes. Patient with high expression of MUC3A should be more frequent follow-up and might benefit less from radiotherapy.

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