scholarly journals YBX1 Enhances Metastasis and Stemness by Transcriptionally Regulating MUC1 in Lung Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Qiang Xie ◽  
Shilei Zhao ◽  
Wenzhi Liu ◽  
Yanwei Cui ◽  
Fengzhou Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cancer Metastasis ◽  
Luciferase Reporter ◽  
Mucin 1 ◽  
Tumor Cell Migration ◽  
Downstream Target ◽  
Lung Cancer Metastasis ◽  
Adenocarcinoma Cells ◽  
Metastasis Model ◽  
Lung Adenocarcinoma Cells

Abnormal expression of the transcription factor Y-box-binding protein-1 (YBX1) is associated with the proliferation, migration, aggressiveness, and stem-like properties of various cancers. These characteristics contribute to the tumorigenesis and metastasis of cancer. We found that the expression levels of Mucin-1 (MUC1) and YBX1 were positively correlated in lung adenocarcinoma cells and lung adenocarcinoma tissue. Our retrospective cohort study of 176 lung adenocarcinoma patients after surgery showed that low expression of both YBX1 and MUC1 was an independent predictor of the prognosis and recurrence of lung adenocarcinoma. In lung adenocarcinoma cells, the silencing/overexpression of YBX1 caused a simultaneous change in MUC1, and MUC1 overexpression partially reversed the decreased tumor cell migration, aggressiveness, and stemness caused by YBX1 silencing. Moreover, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays proved that MUC1 was the downstream target of YBX1 and that YBX1 bound to the -1480~-1476 position in the promoter region of MUC1 to regulate its transcription. Furthermore, in mouse xenograft models and a lung cancer metastasis model, MUC1, which is downstream of YBX1, partially reversed the decreased number and size of tumors caused by YBX1 silencing. In conclusion, our findings indicated a novel mechanism by which YBX1 promotes the stemness and metastasis of lung adenocarcinoma by targeting MUC1 and provided a combination approach for diagnosis different from traditional single tumor biomarkers to predict patient prognosis and provide clinical treatment targets.

scholarly journals PFKFB4 promotes lung adenocarcinoma progression via phosphorylating and activating transcriptional coactivator SRC-2

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiguang Meng ◽  
Xuxin Chen ◽  
Zhihai Han
Keyword(s):  
Lung Adenocarcinoma ◽  
Transcriptional Activity ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Transcriptional Coactivator ◽  
Downstream Target ◽  
Steroid Receptor Coactivator ◽  
Adenocarcinoma Cells ◽  
Family Protein ◽  
Lung Adenocarcinoma Cells

Abstract Background To investigate the role and its potential mechanism of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) in lung adenocarcinoma. Methods Co-immunoprecipitation was performed to analyze the interaction between PFKFB4 and SRC-2. Western blot was used to investigate the phosphorylation of steroid receptor coactivator-2 (SRC-2) on the condition that PFKFB4 was knockdown. Transcriptome sequencing was performed to find the downstream target of SRC-2. Cell Counting Kit-8 (CCK-8) assay, transwell assay and transwell-matrigel assay were used to examine the proliferation, migration and invasion abilities in A549 and NCI-H1975 cells with different treatment. Results In our study we found that PFKFB4 was overexpressed in lung adenocarcinoma associated with SRC family protein and had an interaction with SRC-2. PFKFB4 could phosphorylate SRC-2 at Ser487, which altered SRC-2 transcriptional activity. Functionally, PFKFB4 promoted lung adenocarcinoma cells proliferation, migration and invasion by phosphorylating SRC-2. Furthermore, we identified that CARM1 was transcriptionally regulated by SRC-2 and involved in PFKFB4-SRC-2 axis on lung adenocarcinoma progression. Conclusions Our research reveal that PFKFB4 promotes lung adenocarcinoma cells proliferation, migration and invasion via enhancing phosphorylated SRC-2-mediated CARM1 expression.

Dexmedetomidine upregulates the expression of miR-493-5p, inhibiting growth and inducing the apoptosis of lung adenocarcinoma cells by targeting RASL11B

2021 ◽  
pp. 1-8
Author(s):  
Bo Xu ◽  
Yiling Qian ◽  
Chunxiao Hu ◽  
Yongsheng Wang ◽  
Hong Gao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Luciferase Reporter ◽  
Adenocarcinoma Cell Line ◽  
Expression Levels ◽  
Lung Adenocarcinoma Cell Line ◽  
Adenocarcinoma Cells ◽  
Reporter Assays ◽  
Lung Adenocarcinoma Cells ◽  
High Degree ◽  
Degree Of Similarity

Numerous studies have indicated that microRNAs (miRNAs) play critical roles in the development and progression of cancer. However, how changes to the expression levels of miRNAs in response to dexmedetomidine affects the progression of lung cancer remains poorly understood. In this study, we treated the lung adenocarcinoma cell line-A549 with dexmedetomidine and then examined the changes to the expression levels of miRNAs. We found that one of the most significantly upregulated miRNAs was miR-493-5p, which has an important role in the growth and apoptosis of lung adenocarcinoma (LUAD) cells. In addition, bioinformatics searches and luciferase reporter assays revealed that miR-493-5p targets RASL11B, which has a high degree of similarity to RAS. Finally, database searches revealed that RASL11B is associated with survival of LUAD cells. In conclusion, dexmedetomidine causes changes to the expression levels of miRNAs in LUAD, including significant upregulation of miR-493-5p. MiR-493-5p targets RASL11B, thereby inhibiting cell growth and inducing apoptosis in LUAD.

scholarly journals Fe3O4 magnetic nanoparticle-enhanced radiotherapy for lung adenocarcinoma via delivery of siBIRC5 and AS-ODN

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shuzhen Chen ◽  
Fushi Han ◽  
Dongdong Huang ◽  
Jinqian Meng ◽  
Jiapeng Chu ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Lung Adenocarcinoma ◽  
Targeted Delivery ◽  
Therapeutic Effects ◽  
Tumor Cell Migration ◽  
Lung Cancer Patients ◽  
Tumor Bearing ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Fe3o4 Magnetic Nanoparticle

Abstract Background Radiotherapy is the mainstay treatment for lung adenocarcinoma, yet remains highly susceptible to resistance. Fe3O4 magnetic nanoparticles (MNPs) possess the ability to induce biological therapeutic effects. Herein, the current study set out to explore the effects of Fe3O4 MNPs on radiosensitivity of lung adenocarcinoma cells. Methods Fe3O4 MNPs loaded with both negatively-charged small interfering RNA against baculoviral IAP repeat containing 5 (siBIRC5) and oligodeoxynucleotide antisense (AS-ODN) to generate co-delivery NPs, followed by evaluation. Gel retardation assay was further performed to determine the binding ability of Fe3O4 MNPs to AS-ODN/siBIRC5. The radiosensitizing effect of NPs on lung adenocarcinoma cells was determined in the absence or the presence of NPs or radiotherapy. A549 and H460 tumor-bearing mice were established, where tumor tissues were subjected to immunohistochemistry. Results NPs were successfully prepared and characterized. BIRC5 expression levels were augmented in tissues of lung cancer patients. Fe3O4 MNPs enhanced the uptake of siBIRC5 and AS-ODN by lung adenocarcinoma cells. The presence of NPs under magnetic field reduced the BIRC5 expression and elevated the DR5 expression in lung adenocarcinoma cells. Lung adenocarcinoma cells treated with NPs exhibited inhibited tumor cell migration and increased DNA damage. After magnetic field treatment, tumors were better suppressed in the tumor-bearing mice treated with NPs, followed by radiotherapy. Conclusion Findings obtained in our study indicated that Fe3O4 MNPs-targeted delivery of siBIRC5 and AS-ODN enhances radiosensitivity, providing an innovative solution for the current clinically existing lung adenocarcinoma patients with radiotherapy resistance with a low risk of toxicity.

scholarly journals miR-767-3p Inhibits Growth and Migration of Lung Adenocarcinoma Cells by Regulating CLDN18

2018 ◽  
Vol 26 (4) ◽  
pp. 637-644 ◽  
Author(s):  
Yi Long Wan ◽  
Han Jue Dai ◽  
Wei Liu ◽  
Hai Tao Ma
Keyword(s):  
Lung Adenocarcinoma ◽  
Intercellular Junctions ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Luciferase Reporter Gene ◽  
Cell Growth And Migration ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
And Migration ◽  
Reporter Gene Analysis

Claudin18 (CLDN18) is necessary for intercellular junctions and is reported to be involved in cell migration and metastasis, making it like an oncogene in various cancer types. However, the biological function and regulatory mechanisms of CLDN18 in lung adenocarcinoma are not yet clear. In this study, we found downregulation of miR-767-3p and upregulation of CLDN18 in lung adenocarcinoma tissue and cell lines. In addition, there was a negative correlation between the expression of miR-767-3p and CLDN18 in lung adenocarcinoma. Double luciferase reporter gene analysis showed that miR-767-3p modulates the expression of CLDN18 by binding its 3′-untranslated regions (3′-UTR). Knockdown of CLDN18 results in a decrease in the growth, migration, and invasion of lung adenocarcinoma cells. Although overexpression of miR-767-3p inhibits lung adenocarcinoma cell growth and migration, these effects can be rescued by reexpressing CLDN18. In summary, the data suggest that miR-767-3p inhibits tumor cell proliferation, migration, and invasion by targeting CLDN18, providing a promising therapeutic target for lung adenocarcinoma.

scholarly journals Overexpression of RhoV Promotes the Progression and EGFR-TKI Resistance of Lung Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Hongjin Chen ◽  
Ruixue Xia ◽  
Long Jiang ◽  
Yong Zhou ◽  
Haojun Xu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Critical Role ◽  
Migration And Invasion ◽  
Tumor Cell Migration ◽  
Adenocarcinoma Cells ◽  
Tki Resistance ◽  
Lung Adenocarcinoma Cells ◽  
Egfr Tki

BackgroundThe Rho GTPase family with ~20 member genes play central roles in a wide variety of cellular processes and tumor cell migration and metastasis. Different Rho GTPase may play different roles in the progression of lung adenocarcinoma.MethodsWe comprehensively examined the expression of all Rho GTPase family member genes in a panel of lung adenocarcinoma patient’s tumors and matched normal tissues. We next investigated the critical role of RhoV in different lung adenocarcinoma cells and animal models.ResultsRhoV was identified as one of the most significantly overexpressed Rho GTPases in lung adenocarcinoma and associated with patients’ survival. Silencing RhoV expression inhibits proliferation, migration and invasion, and tumorigenicity capacities of lung adenocarcinoma cells. Moreover, knockdown RhoV promoted the sensitivity of EGFR-TKI in the gefitinib resistant PC9 cells (PC9-GR) and aggravated gefitinib-induced lung cancer cell apoptosis both in PC9 and PC9-GR cells. Our data also indicated that RhoV induced progression and EGFR-TKI resistance of lung adenocarcinoma may be related to the activation of the AKT/ERK pathway.ConclusionOverexpression of RhoV in lung adenocarcinoma promotes the progression and EGFR-TKI resistance, suggesting RhoV is a promising prognosis and therapeutic target of lung adenocarcinoma.

scholarly journals Hsa_circ_0020850 promotes the malignant behaviors of lung adenocarcinoma by regulating miR-326/BECN1 axis

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaoju Li ◽  
Shengtian Su ◽  
Dan Ye ◽  
Zhigao Yu ◽  
Wenjing Lu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Mice Model ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Abstract Background Circular RNAs (circRNAs) are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma. However, the function and underlying mechanism of circ_0020850 in lung adenocarcinoma remain unknown. Methods The levels of circ_0020850, microRNA-326 (miR-326), and Beclin1 (BECN1) were analyzed by real-time quantitative polymerase chain reaction and western blot analyses. The migration and invasion were determined by wound healing and transwell assays, respectively. Colony formation assay was used to assess cell proliferation ability. The angiogenic ability was analyzed by Matrigel angiogenesis assay. The apoptosis rate was calculated by flow cytometry assay. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were conducted to confirm the interaction relationship among circ_0020850, miR-326, and BECN1. A xenograft mice model was established to assess the role of circ_0020850 in vivo. Results We found that circ_0020850 was obviously overexpressed in lung adenocarcinoma tissues and cells. Knockdown of circ_0020850 inhibited migration, invasion, proliferation, and angiogenesis but induced apoptosis in lung adenocarcinoma cells in vitro, as well as curbed tumor growth in vivo. MiR-326 was a target of circ_0020850, and knockdown of miR-326 abolished the suppression effect of circ_0020850 on the malignant behaviors of lung adenocarcinoma cells. Additionally, miR-326 could negatively regulate BECN1 expression, thereby regulating lung adenocarcinoma cell phenotypes. Importantly, circ_0020850 could directly bind to miR-326 and thus relieve miR-326-mediated inhibition on BECN1. Conclusion Circ_0020850 promoted the malignant development of lung adenocarcinoma by regulating miR-326/BECN1 axis, indicating that circ_0020850 might serve as a promising target for the diagnosis and treatment of lung adenocarcinoma patients.

scholarly journals MiR-326 mediates malignant biological behaviors of lung adenocarcinoma by targeting ZEB1

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110093
Author(s):  
Mingxin Liu ◽  
Hong Wu ◽  
Yiqiang Liu ◽  
Yan Tan ◽  
Songtao Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Invasion And Migration ◽  
Transwell Invasion Assay ◽  
Enhancer Binding Protein ◽  
Adenocarcinoma Cells ◽  
And Migration ◽  
Related Proteins

MiR-326 functions as an antioncogene in the several types of cancer. However, the underling mechanisms through which miRNA-326 regulates the anti-carcinogenesis of lung adenocarcinoma have remained elusive. The aim of this study was to explore the role and regulatory mechanism of miR-326 in cell proliferation, invasion, migration and apoptosis in lung adenocarcinoma. Quantitative real-time PCR (qRT-PCR) was used to detect the expression pattern of miR-326 in human bronchial epithelial cells (HBES-2B), 4 kinds of lung adenocarcinoma cell lines (H23, H1975, H2228, H2085) and 20 lung adenocarcinoma tissues. Then, H23 cells were infected with miR-326 mimics, miR-326 inhibitors and si-ZEB1 to build up-regulated miR-326 cell lines, down-regulated ZEB1(zinc-finger-enhancer binding protein 1)cell lines, simultaneous down-regulated ZEB1 and miR-326 cell lines. Moreover, CCK-8 assay, transwell invasion assay, wound healing assay and flow cytometry assay were employed to examine the effects of miR-326 and ZEB1 on the proliferation, invasion, migration and apoptosis abilities of H23 cells. Western blot was performed to explore the effects of miR-326 and ZEB1 on the expression of invasion and migration related proteins N-cadherin, E-cadherin, MMP7, MMP13, SLUG and apoptotic proteins PARP, BAX. On the mechanism, a dual-luciferase reporter gene was used to measure the target relationship between miR-326 and ZEB1. MiR-326 expression was significantly downregulated in lung adenocarcinoma tissues and cells. Overexpression of miR-326 significantly inhibited the malignant behaviors of H23 cells. Mechanically, luciferase reporter assay showed that ZEB1 was a direct target of miR-326. MiR-326 mimic downregulated the expression of ZEB1. Furthermore, knocking down ZEB1 strongly inhibited the proliferation, invasion and migration of H23 cells but promoted apoptosis. MiR-326 could target ZEB1 to inhibit the proliferation, invasion and migration of lung adenocarcinoma cells and promote apoptosis, which is a potential therapeutic target for lung adenocarcinoma.

scholarly journals PD-L1 lncRNA splice isoform promotes lung adenocarcinoma progression via enhancing c-Myc activity

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shuang Qu ◽  
Zichen Jiao ◽  
Geng Lu ◽  
Bing Yao ◽  
Ting Wang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Lung Adenocarcinoma ◽  
Solid Tumors ◽  
Immune Checkpoint ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Non Coding Rna ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Long Non Coding Rna

Abstract Background Although using a blockade of programmed death-ligand 1 (PD-L1) to enhance T cell immune responses shows great promise in tumor immunotherapy, the immune-checkpoint inhibition strategy is limited for patients with solid tumors. The mechanism and efficacy of such immune-checkpoint inhibition strategies in solid tumors remains unclear. Results Employing qRT-PCR, Sanger sequencing, and RNA BaseScope analysis, we show that human lung adenocarcinoma (LUAD) all produce a long non-coding RNA isoform of PD-L1 (PD-L1-lnc) by alternative splicing, regardless if the tumor is positive or negative for the protein PD-L1. Similar to PD-L1 mRNA, PD-L1-lnc in various lung adenocarcinoma cells is significantly upregulated by IFNγ. Both in vitro and in vivo studies demonstrate that PD-L1-lnc increases proliferation and invasion but decreases apoptosis of lung adenocarcinoma cells. Mechanistically, PD-L1-lnc promotes lung adenocarcinoma progression through directly binding to c-Myc and enhancing c-Myc transcriptional activity. Conclusions In summary, the PD-L1 gene can generate a long non-coding RNA through alternative splicing to promote lung adenocarcinoma progression by enhancing c-Myc activity. Our results argue in favor of investigating PD-L1-lnc depletion in combination with PD-L1 blockade in lung cancer therapy.

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