<i>In vivo</i>selection for spine-derived highly metastatic lung cancer cells is associated with increased migration, inflammation and decreased adhesion

Cai, Xiaopan; Luo, Jian; Yang, Xianghong; Deng, Huayun; Zhang, Jishen; Li, Shichang; Wei, Haifeng; Yang, Cheng; Xu, Leqin; Jin, Rongrong; Li, Zhenxi; Wang, Zhou; Ding, Jiandong; Chu, Jianjun; Jia, Lianshun; Jia, Qi; Tan, Chao; Liu, Mingyao; Xiao, Jianru

doi:10.18632/oncotarget.4416

Cited by 30 publications

(31 citation statements)

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“…To identify essential regulators required for lung cancer bone metastasis, a murine spinal metastasis of A549 cells was established, from which two A549 cell lines either without metastasis or with spinal metastasis were obtained . It was found that migration and invasion increased and cell adhesion decreased in metastatic cells.…”

Section: Resultsmentioning

confidence: 99%

FOXD3 Suppresses Tumor-Initiating Features in Lung Cancer via Transcriptional Repression of WDR5

et al. 2019

Stem Cells

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The tumor-initiating cells (TICs) are a cell population that can initiate tumor occurrence, mediate drug resistance, and give rise to metastasis. FOXD3 is a forkhead box (Fox) transcription factor family that regulates the pluripotency of embryonic stem cell and tumorigenicity. However, it is unclear whether FOXD3 plays any role in TIC and tumor metastasis. The functional analysis of FOXD3 was performed by oncospheres formation and redifferentiation, drug resistance assay, and cell migration. Global genomic RNA-Seq and ChIP-Seq analysis were used to identify the direct target of FOXD3 in lung cancer. We demonstrated that downregulation of FOXD3 in TICs was positively correlated with higher histologic grades and positive lymph node metastasis. FOXD3 repressed TIC expansion and cell migration, drug resistance, and osteoclasts in vitro and in vivo. Mechanically, we found that FOXD3 represses WDR5, which regulates TIC-related signaling pathway. Moreover, WDR5 were positively correlated with the TIC abundance and tumor progression. Besides, patients with high expression of WDR5 presented a poorer overall survival. FOXD3 may suppress TIC accumulation by repressing the expression of WDR5 in lung cancer. STEM CELLS 2019;37:582-592 SIGNIFICANCE STATEMENTCurrently, it is unclear whether FOXD3 plays any role in the tumor-initiating cells (TIC) and tumor metastasis. This study found that FOXD3 repressed TIC expansion and cell migration, drug resistance, and osteoclasts in vitro and in vivo. Mechanically, it was found that FOXD3 represses WDR5, which regulates the TIC-related signaling pathway. Collectively, the work defined that FOXD3 may suppress TIC accumulation by repressing the expression of WDR5 in lung cancer.

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Section: Resultsmentioning

confidence: 99%

FOXD3 Suppresses Tumor-Initiating Features in Lung Cancer via Transcriptional Repression of WDR5

et al. 2019

Stem Cells

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“…Suzuki et al (34) demonstrated that ANLN was overexpressed in the majority of primary NSCLCs, and the endogenous expression of ANLN in the nucleus was significantly associated with poor prognosis in patients with NSCLC. Cellular retinoic acid binding protein 2 (CRABP2) expression is markedly increased in lung adenocarcinoma (35) and the expression of cystatin SN (CST1) is closely associated with tumor metastasis properties in A549L6 cells (36). In the present study, CP, HS6ST2, TMPRSS4, ANLN, CRABP2 and CST1 were significantly upregulated in lung adenocarcinoma compared with corresponding healthy lung tissues, indicating that the overexpressed outlier genes may serve important roles in the development of lung adenocarcinoma.…”

Section: Discussionsupporting

confidence: 51%

Integrated analysis reveals candidate genes and transcription factors in lung adenocarcinoma

Chen¹,

Gao²,

Ji³

et al. 2017

Molecular Medicine Reports

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Lung adenocarcinoma is the most common type of non‑small cell lung cancer in Asia. Therefore, it is important to improve understanding of the underlying transcriptional regulatory mechanisms involved. The present study aimed to identify potential candidate genes and transcription factors (TFs) associated with the disease. Four gene expression profiles were downloaded from the Gene Expression Omnibus database, which included 141 lung adenocarcinoma patients and 191 healthy controls. The differentially expressed genes (DEGs) were screened out and functional annotation was performed. In addition, TFs were identified and a global transcriptional regulatory network was constructed. Integrated analysis gave rise to a total of 1,238 DEGs in lung adenocarcinoma when compared with healthy tissues, including 970 upregulated and 268 downregulated DEGs. The six overexpressed outlier genes of ceruloplasmin, heparan sulfate 6‑O‑sulfotransferase 2, transmembrane protease serine 4, anillin actin binding protein, cellular retinoic acid binding protein 2 and cystatin SN may serve important roles in the development of lung adenocarcinoma. In addition, the downregulation of carbonic anhydrase 4 and S100 calcium binding protein A12 may render these effective diagnostic biomarkers. The results of the transcriptional regulatory network demonstrated that the hub nodes were sex determining region Y‑box 10, Spi‑B transcription factor and nuclear receptor subfamily 4 group A member 2. The four TFs, forkhead box D1, E74‑like ETS transcription factor 5, homeobox A5 and kruppel‑like factor 5, may warrant future investigations into their function in disease development. In conclusion, the present study provided for further studies a list of candidate genes and TFs for the detection and treatment of lung adenocarcinoma.

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“…When Lewis lung cancer cell metastasize to bone, such algogenic substances as endothelins, prostaglandins, proteases, protons, bradykinin, and tyrosine kinase activators will be released by the cancer cells as well as their associated stromal cells, leading to induction of sensitization and activation of sensory nerves that innervate the bone [33, 34]. In this way, we believed that miR-93 suppressing Smad5 may contribute to the exacerbation of BCP.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-93-5p may participate in the formation of morphine tolerance in bone cancer pain mouse model by targeting Smad5

Xiao

Lou

et al. 2016

Oncotarget

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ObjectiveIn this study, we aim to find out the role of microRNA-93-5p (miR-93) and Smad5 in morphine tolerance in mouse models of bone cancer pain (BCP).ResultsAt 7 days after injection of morphine, the PMWT showed no significant difference between the morphine model group and the saline model group (P < 0.05), suggesting that morphine tolerance had formed in the morphine model group. The morphine model group had higher miR-93 expression and lower Smad5 mRNA expression than the saline model group. Smad5 is a downstream target gene of miR-93. At 7, 9 and 14 days after injection of lentiviruses, the L/anti-miR-93 group had the lowest PMWTs, while the Smad5 shRNA group presented the highest PMWTs among these five groups (all P < 0.05).MethodsWe built mouse models of BCP and morphine tolerance and recorded 50% PMWT. After 6 days of modeling, we set saline control group, morphine control, saline model group and morphine model group (morphine tolerance emerged). We performed luciferase reporter gene assay to verify the relation between miR-93 and Smad5. After lentivirus transfection, the mice with morphine tolerance were assigned into L/anti-miR-93 group, Smad5 shRNA group, L/anti-miR-93 + Smad5 shRNA group, blank group and PBS control group. RT-qPCR, Western Blot assay and immumohistochemical staining were performed to observe the changes of miR-93 and Smad5.ConclusionUp-regulation of miR-93 may contribute to the progression of morphine tolerance by targeting Smad5 in mouse model of BCP.

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In vivoselection for spine-derived highly metastatic lung cancer cells is associated with increased migration, inflammation and decreased adhesion

Cited by 30 publications

References 50 publications

FOXD3 Suppresses Tumor-Initiating Features in Lung Cancer via Transcriptional Repression of WDR5

FOXD3 Suppresses Tumor-Initiating Features in Lung Cancer via Transcriptional Repression of WDR5

Integrated analysis reveals candidate genes and transcription factors in lung adenocarcinoma

MicroRNA-93-5p may participate in the formation of morphine tolerance in bone cancer pain mouse model by targeting Smad5

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