scholarly journals Upregulation of long intergenic noncoding RNA LINC00092 indicates favorable survival in lung adenocarcinoma via tumor growth inhibition

2019 ◽  
Author(s):  
Mingyan Jiang ◽  
Ke Wang ◽  
Ziwen Zhao ◽  
Yujun Li ◽  
Hua He ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Noncoding Rna ◽  
Lung Squamous Cell Carcinoma ◽  
Molecular Therapy ◽  
Normal Lung ◽  
Cox Regression Analysis ◽  
Long Intergenic Noncoding Rna

Abstract Background Long intergenic noncoding RNA 00092 (LINC00092) is a recently identified novel RNA that acts on cancer-associated fibroblasts (CAFs) to drive the progression of ovarian cancer. Because CAFs also play a vital role in lung cancer, we hypothesized that LINC00092 is associated with lung cancer.Methods The expression level of LINC00092 was examined in 93 cases of non-small cell lung cancer (NSCLC) tumor tissues and adjacent normal lung tissues, and its clinical effect on prognosis was evaluated using the Kaplan-Meier method, log-rank test and Cox regression analysis based on The Cancer Genome Atlas (TCGA) data. The effect of LINC00092 on tumor growth was further assessed in vitro .Results LINC00092 was significantly downregulated in 76.3% (71/93) of lung cancer tissues compared to that in their normal counterparts ( P < 0.001), and high expression of LINC00092 led to a better prognosis with increased survival time (1632 days vs. 1171 days; P = 0.087) and decreased mortality (hazard rate, HR = 0.73, 95%CI = 0.51-1.05) than low expression in lung adenocarcinoma (LUAD) but not in lung squamous cell carcinoma (LSCC) patients. Additionally, upregulation of LINC00092 inhibited LUAD cell proliferation and tumorigenic ability in vitro .Conclusions LINC00092 is an indicator of favorable LUAD prognosis. Targeted molecular therapy directed at LINC00092 upregulation may be a valuable strategy to fight LUAD.

scholarly journals KRT6A Promotes EMT and Cancer Stem Cell Transformation in Lung Adenocarcinoma

2020 ◽  
Vol 19 ◽  
pp. 153303382092124
Author(s):  
Bin Yang ◽  
Wei Zhang ◽  
Mengmeng Zhang ◽  
Xuhong Wang ◽  
Shengzu Peng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Lung Adenocarcinoma ◽  
Biological Function ◽  
Epithelial Mesenchymal Transition ◽  
The Cancer Genome Atlas ◽  
Normal Lung ◽  
Mesenchymal Transition

Aim: Keratin 6A is a type II cytokeratin which is important in forming nail bed, filiform papillae, the epithelial lining of oral mucosa, and esophagus; recently, keratin 6A was found hyperexpressed in different types of cancer. But, the biological function of keratin 6A in lung adenocarcinoma still remains unclear. Therefore, in current study, we investigated the biological role of keratin 6A in lung adenocarcinoma. Methods: By utilizing The Cancer Genome Atlas database, we investigated the expression profile of keratin 6A and its relationship with other clinical parameters in lung adenocarcinoma. The biological function of keratin 6A in lung adenocarcinoma was also investigated by using A549 and PC-9 lung cancer cell lines in vitro. Results: Our data indicate that, compared with normal lung tissue samples, keratin 6A was hyperexpressed in lung adenocarcinoma. Moreover, keratin 6A hyperexpression was positively correlated with lymph node positive and aggressive tumor T stage. Keratin 6A knockdown inhibited the cell proliferation, migration, and colony formation ability but not cell death in lung adenocarcinoma cells. In addition, we found keratin 6A exerted its phenotype via promoting cancer stem cells (CXCR4high/CD133high) transformation and epithelial–mesenchymal transition. Conclusion: In conclusion, current study suggests that hyperexpressed keratin 6A in lung adenocarcinoma promotes lung cancer proliferation and metastasis via epithelial–mesenchymal transition and cancer stem cells transformation.

scholarly journals The Long Intergenic Noncoding RNA 00707 Promotes Lung Adenocarcinoma Cell Proliferation and Migration by Regulating Cdc42

2018 ◽  
Vol 45 (4) ◽  
pp. 1566-1580 ◽  
Author(s):  
Tianshi Ma ◽  
Hongwei Ma ◽  
Zigui Zou ◽  
Xuezhi He ◽  
Yanhua Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Lung Adenocarcinoma ◽  
Microarray Analysis ◽  
Noncoding Rna ◽  
Target Gene ◽  
Qrt Pcr ◽  
Long Intergenic Noncoding Rna

Background/Aims: Lung cancer (LC) is a serious disease with high morbidity and mortality. Long noncoding RNAs (lncRNAs) have garnered attention because they participate in diverse human disorders, including cancer. Our study examined the long intergenic noncoding RNA 00707 (LINC00707). The effects of LINC00707 on lung adenocarcinoma (LAD) and molecular mechanisms are unclear. This study is aimed to investigate the role of LINC00707 in the malignant processes of LAD. Methods: Quantitative reverse transcription PCR (qRT-PCR) was used to examine the expression level of LINC00707 in tissues and cell lines. The association of LINC00707 expression and postoperative prognosis was analyzed by the Kaplan-Meier method and log-rank test. Cell proliferation was evaluated in vitro and in vivo. Transwell assays were performed to examine cell migration. Cell cycle and apoptosis was determined by flow -cytometric and western blot analyses. Microarray analysis was conducted to screen for the downstream target gene Cdc42 of LINC00707, which was identified by qRT-PCR, functional analysis, and rescue experiment. Results: The expression level of LINC00707 was clearly upregulated in LAD tissues compared to that in corresponding normal tissues. Its overexpression was related to advanced TNM stage, larger tumor size, lymphatic metastasis, and poor prognosis. Functional assays revealed that LINC00707 knockdown repressed LAD cell proliferation both in vitro and in vivo. This process may involve the inducing of G1 arrest and apoptosis. Moreover, cell migration was impaired after LINC00707 inhibition. Microarray analysis and rescue assays suggested that Cdc42 is an important target gene involved in the carcinogenesis of LINC00707. Conclusions: In summary, LINC00707 is a noncoding oncogene that exerts important regulatory functions in LAD, suggesting its potential as a biomarker in the prognosis and treatment of LAD.

scholarly journals The Sulfotransferase SULT1C2 Is Epigenetically Activated and Transcriptionally Induced by Tobacco Exposure and Is Associated with Patient Outcome in Lung Adenocarcinoma

2021 ◽  
Vol 19 (1) ◽  
pp. 416
Author(s):  
Candace Johnson ◽  
Daniel J. Mullen ◽  
Suhaida A. Selamat ◽  
Mihaela Campan ◽  
Ite A. Offringa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Lung Adenocarcinoma ◽  
Binding Site ◽  
Cell Line ◽  
Cigarette Smoke ◽  
Cell Lines ◽  
Normal Lung ◽  
Tobacco Exposure

Lung cancer is the leading cause of cancer-related death. Tobacco exposure is associated with 80–90% of lung cancer cases. The SULT1C2 sulfotransferase modifies xenobiotic compounds to enhance secretion but can also render these compounds carcinogenic. To determine if SULT1C2 contributes to tobacco-related carcinogenesis in the lung, we analyzed the expression and epigenetic state of SULT1C2 in human lung adenocarcinoma (LUAD) samples and in LUAD cell lines exposed to cigarette smoke condensate (CSC). SULT1C2 expression was significantly positively correlated to overall LUAD patient survival in smokers, was elevated in LUAD tumors compared to adjacent non-tumor lung, and was significantly correlated with levels of patient exposure to tobacco smoke. SULT1C2 promoter DNA methylation was inversely correlated with expression in LUAD, and hypomethylation of the SULT1C2 promoter was observed in Asian patients, as compared to Caucasians. In vitro analysis of LUAD cell lines indicates that CSC stimulates expression of SULT1C2 in a dose-dependent and cell-line-specific manner. In vitro methylation of the SULT1C2 promoter significantly decreased transcriptional activity of a reporter plasmid, and SULT1C2 expression was activated by the DNA demethylating agent 5-Aza-2′-deoxycytidine in a cell line in which the SULT1C2 promoter was hypermethylated. An aryl hydrocarbon receptor (AHR) binding site was detected spanning critical methylation sites upstream of SULT1C2. CSC exposure significantly increased AHR binding to this predicted binding site in the SULT1C2 promoter in multiple lung cell lines. Our data suggest that CSC exposure leads to activation of the AHR transcription factor, increased binding to the SULT1C2 promoter, and upregulation of SULT1C2 expression and that this process is inhibited by DNA methylation at the SULT1C2 locus. Additionally, our results suggest that the level of SULT1C2 promoter methylation and gene expression in normal lung varies depending on the race of the patient, which could in part reflect the molecular mechanisms of racial disparities seen in lung cellular responses to cigarette smoke exposure.

scholarly journals Upregulation of Linc00284 Promotes Lung Cancer Progression by Regulating the miR-205-3p/c-Met Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Wang Sheng ◽  
Weixi Guo ◽  
Fang Lu ◽  
Hongming Liu ◽  
Rongmu Xia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Significant Negative Correlation ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Expression Levels ◽  
Incidence And Mortality

Lung cancer (LC) is a malignant tumor with the highest incidence and mortality rates worldwide. Linc00284, a long non-coding RNA, is a newly discovered regulator of LC. This study aimed to explore the role of Linc00284 in LC progression. Gene expression levels were detected by RT-qPCR and/or western blot analysis. Cell migratory and invasive capabilities were measured by wound healing and transwell assays. Subcutaneous xenograft models were constructed to examine tumor growth of LC cells. Data showed that Linc00284 was significantly upregulated in LC tissues compared to adjacent normal lung tissues and predicted poor prognosis in patients with LC. In vitro, Linc00284 was highly expressed in LC cells and was mainly localized in the cytoplasm. Mechanistically, Linc00284 directly bound to miR-205-3p, leading to the upregulation of c-Met expression. A significant negative correlation was observed between Linc00284 and miR-205-3p expression levels, and the Linc00284 level was positively correlated with the c-Met expression. Linc00284/miR-205-3p/c-Met regulatory axis promotes LC cell proliferation, migration, and invasion. Furthermore, the in vivo results indicated that Linc00284 knockdown markedly suppressed tumor growth. Taken together, these data suggest that Linc00284 facilitates LC progression by targeting the miR-205-3p/c-Met axis, which may be a potential target for LC treatment.

scholarly journals SPAG1 Inhibits Cell Proliferation and Tumor Growth of Lung Adenocarcinoma via the AKT/mTORC1 Signaling Axis

2021 ◽  
Author(s):  
Aili Li ◽  
Kai Huang ◽  
Jinyong Guo ◽  
Youru Wu ◽  
Qiufeng He ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Normal Lung ◽  
Multiple Cancer ◽  
Tumor Xenografts ◽  
Favorable Prognosis ◽  
Mtorc1 Signaling ◽  
Signaling Axis

Abstract Background Sperm-associated antigen 1 (SAPG1) expression is increased in multiple cancer tissues, but the role and mechanisms of SPAG1 in lung cancer remain unknown. The present study was aimed to investigate SPAG1’s function and mechanisms in lung adenocarcinoma (LUAD). MethodsSPAG1 expression in LUAD tissues was evaluated by analyzing three LUAD datasets, and its association with prognosis of patients with LUAD was accessed by using Kaplan-Meier Plotter. The role of SPAG1 and its mechanisms were investigated in LUAD cells in vitro. The effect of SPAG1 on tumor growth was evaluated in LUAD tumor xenografts. In addition, the molecular domain involved in the regulation of cell proliferation was mapped. ResultsThe bioinformatical results showed that SPAG1 expression was increased significantly in LUAD tissues compared with normal lung tissues, and its high expression was associated with favorable prognosis, including overall survival (OS), first progression (FP) and post-progression survival (PPS). The results of in vitro experiments showed that SPAG1 suppressed cell proliferation, but enhanced autophagy via inhibiting AKT/mechanistic target of rapamycin (mTOR) complex 1 signaling axis, and that the region of 130~170 amino acid residues in SPAG1 is involved in the regulation of AKT and cell proliferation. The results of tumor xenografts demonstrated that SPAG1 knockdown promotes LUAD tumor growth and enhances AKT/mTORC1 signaling. ConclusionSPAG1 is upregulated in LUAD tissues and associated with favorable prognosis of patients with LUAD, and plays an inhibitory role in cell proliferation and tumor growth of LUAD through the AKT/mTORC1 signaling axis.

scholarly journals Ezh2 Inhibitors Reverse Resistance to Gefitinib in Primary Egfr Wild-type Lung Cancer Cells

2020 ◽  
Author(s):  
Hao Gong ◽  
Yongwen Li ◽  
Yin Yuan ◽  
Weiting Li ◽  
Hongbing Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cell Viability ◽  
Lung Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Egfr Mutations ◽  
Wild Type ◽  
Egfr Tkis

Abstract Background: Lung cancer is the leading cause of cancer-related death worldwide. Non–small-cell lung cancer (NSCLC) is the most common type of lung cancer. Traditional anticancer therapies involving epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) have been proven beneficial in the treatment of patients with EGFR mutations. However, patients with EGFR wild-type NSCLC usually fail to respond to EGFR-TKIs. Enhancer of zeste homolog 2 (EZH2), a key molecule of the PRC2 complex, plays an important role in epigenetic regulation and is overexpressed in various tumors. EZH2 inhibitors sensitize various types of tumor cells to antitumor drugs. Therefore, this study aimed to investigate whether the EZH2 inhibitors GSK343 and DZNep, whencombined with gefitinib, can reverse EGFR-TKI resistance in EGFR wild-type NSCLC. Methods:EZH2 expression was evaluated using the RNA sequencing dataset of NSCLC patients (502 lung squamous cell carcinoma cases including 49 paracancerous lung tissues and 513 lung adenocarcinoma cases including 59 paracancerous lung tissues) from The Cancer Genome Atlas (TCGA). We simultaneously also verified EZH2 expressionin 40 NSCLC samples and their corresponding paracancerous lung tissues from our institution via quantitative PCR. The lung adenocarcinoma cell lines A549 and H1299 were treated with EZH2-specific small interfering RNA or EZH2 inhibitors and subjected to analyses of cell viability and apoptosis as well as of EGFR pathway protein expressions by western blotting. Results: EZH2 was upregulated in human NSCLC tissues and was correlated with poor prognosis in patients with lung adenocarcinoma based on data from both TCGA and our institution. Both EZH2 inhibitors sensitized A549 and H1299 cells to gefitinib and suppressed cell viability and proliferation in vitroby downregulating the phosphorylation of EGFR and AKT and inducing cell apoptosis. Co-administration of EZH2 inhibitors (GSK343 or DZNep) with gefitinib exerted stronger inhibitory effects on tumor activity, cell proliferation, and cell migration than single drug administration in vitro and in vivo.Conclusion: Co-administration of EZH2 inhibitors with EGFR-TKIs may be feasible for the treatment of EGFR wild-type NSCLC in patients who refuse traditional chemotherapy.

scholarly journals The Sulfotransferase SULT1C2 is Epigenetically Activated and Transcriptionally Induced by Tobacco Exposure and is Associated with Patient Outcome in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Candace Johnson ◽  
Daniel J. Mullen ◽  
Suhaida A. Selamat ◽  
Mihaela Campan ◽  
Ite A. Offringa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Lung Adenocarcinoma ◽  
Binding Site ◽  
Cell Line ◽  
Cigarette Smoke ◽  
Cell Lines ◽  
Normal Lung ◽  
Tobacco Exposure

Abstract Lung cancer is the leading cause of cancer-related death. Tobacco exposure is associated with 80–90% of lung cancer cases. The SULT1C2 sulfotransferase modifies xenobiotic compounds to enhance secretion but can also render these compounds carcinogenic. To determine if SULT1C2 contributes to tobacco-related carcinogenesis in the lung, we analyzed the expression and epigenetic state of SULT1C2 in human patients in relation to smoking history as well as lung adenocarcinoma (LUAD) cell lines exposed to cigarette smoke condensate (CSC). SULT1C2 expression was significantly positively correlated to overall LUAD patient survival in smokers, was elevated in LUAD tumors, and was significantly correlated with levels of patient exposure to tobacco smoke. SULT1C2 promoter DNA methylation was inversely correlated with expression in LUAD and hypomethylation of the SULT1C2 promoter was observed in Asian patients, as compared to Caucasians. In vitro analysis of LUAD cell lines indicates that CSC stimulates expression of SULT1C2 in a dose-dependent and cell-line specific manner. In vitro methylation of the SULT1C2 promoter significantly decreased transcriptional activity or a reporter plasmid and SULT1C2 expression was activated by the DNA demethylating agent 5-Aza-2’-deoxycytidine in a cell line in which the SULT1C2 promoter was hypermethylated. An aryl hydrocarbon receptor (AHR) binding site was detected spanning critical methylation sites upstream of SULT1C2. CSC exposure significantly increased AHR binding to this predicted binding site in the SULT1C2 promoter in multiple lung cell lines. Our data suggests that CSC exposure leads to activation of the AHR transcription factor, increased binding to the SULT1C2 promoter, and upregulation of SULT1C2 expression, and that this process is inhibited by DNA methylation at the SULT1C2 locus. Additionally, our results suggest that the level of SULT1C2 promoter methylation and gene expression in normal lung varies depending on the race of the patient, which could in part reflect the molecular mechanisms of racial disparities seen in lung cellular responses to cigarette smoke exposure.

scholarly journals Silencing of LINC01279 is activated apoptosis and autophagy in lung cancer by regulating FAK/ERK via SIN3A

2021 ◽  
Author(s):  
Wenmei Su ◽  
Jiancong Wu ◽  
Xiaobi Huang ◽  
Xiaofang Li ◽  
Honglian Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
In Situ Hybridization ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Noncoding Rna ◽  
Lung Cancer Cells ◽  
Loss Of Function

Abstract Background: In human lung adenocarcinoma (LUAD) tissues, Long noncoding RNA LINC01279 is significantly upregulated. However, the functions of LINC01279 in LUAD is yet to be clarified.Methods: In situ hybridization was employed to investigate the difference between expression of LINC01279 in LUAD and in normal tissues. The result of in situ hybridization is verified by qRT-PCR. Cytoplasmic and nuclear experiments showed that LINC01279 was mainly located in the cytoplasm of lung cancer cells. The loss of function experiment showed that LINC01279 could inhibit the proliferation, colony formation, invasion and migration of lung cancer cells. The interaction between SIN3A and LINC01279 was confirmed by RIP test. At the same time, through western bolt, we found that LINC01279 plays a key role in the regulation of apoptosis and autophagy in lung adenocarcinoma.Results: Our study confirmed that LINC01279 was upregulated in LUAD tissues, the knocking-down of which significantly inhibited the growth of LUAD cancer cells both in vitro and in vivo. Mechanistic investigations revealed that LINC01279 could directly interact with SIN3A and modulate the FAK and ERK protein expression in the cytoplasm. Moreover, the proteins of PARP and LC3B, P62, Beclin-1, respectively related with apoptosis and autophagy, were changed after LINC01279 siRNA. Conclusions: Taken together, our research found that LINC01279 which is significantly up-regulated in LUAD tissues and cell lines, and promotes the changes of FAK and ERK proteins in downstream pathways by combining with SIN3A, promotes the proliferation of LUAD cells, and inhibits apoptosis and autophagy. The results of this work illustrated how LINC01279 is part of a regulatory network that contributes to the oncogenesis of LUAD and proposed LINC01279 could be a potential target for LUAD diagnosis and treatment.

scholarly journals LINC00958 promotes the proliferation of TSCC via miR-211-5p/CENPK axis and activating the JAK/STAT3 signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bo Jia ◽  
Junfeng Dao ◽  
Jiusong Han ◽  
Zhijie Huang ◽  
Xiang Sun ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Xenograft Model ◽  
Tumor Xenograft ◽  
Luciferase Reporter ◽  
Cell Cycle Regulators ◽  
Normal Tissues ◽  
Stat3 Signaling ◽  
Long Intergenic Noncoding Rna

Abstract Background Tongue squamous cell carcinoma (TSCC) is one of the most common oral tumors. Recently, long intergenic noncoding RNA 00958 (LINC00958) has been identified as an oncogene in human cancers. Nevertheless, the role of LINC00958 and its downstream mechanisms in TSCC is still unknown. Methods The effect of LINC00958 on TSCC cells proliferation and growth were assessed by CCK-8, colony formation, 5-Ethynyl-2′-deoxyuridline (EdU) assay and flow cytometry assays in vitro and tumor xenograft model in vivo. Bioinformatics analysis was used to predict the target of LINC00958 in TSCC, which was verified by RNA immunoprecipitation and luciferase reporter assays. Results LINC00958 was increased in TSCC tissues, and patients with high LINC00958 expression had a shorter overall survival. LINC00958 knockdown significantly decreased the growth rate of TSCC cells both in vitro and in vivo. In mechanism, LINC00958 acted as a ceRNA by competitively sponging miR-211-5p. In addition, we identified CENPK as a direct target gene of miR-211-5p, which was higher in TSCC tissues than that in adjacent normal tissues. Up-regulated miR-211-5p or down-regulated CENPK could abolish LINC00958-induced proliferation promotion in TSCC cells. Furthermore, The overexpression of CENPK promoted the expression of oncogenic cell cycle regulators and activated the JAK/STAT3 signaling. Conclusions Our findings suggested that LINC00958 is a potential prognostic biomarker in TSCC.

scholarly journals POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ronggang Luo ◽  
Yi Zhuo ◽  
Quan Du ◽  
Rendong Xiao
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Cancer Tissues

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

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