STEAP1 facilitates metastasis and epithelial–mesenchymal transition of lung adenocarcinoma via the JAK2/STAT3 signaling pathway

Huo, Shufen; Shang, W.; Yu, Min; Ren, Xiaoping; Wen, Hongxia; Chai, Chunyan; Sun, Li; Hui, Ke; Liu, Ling-Hua; Wei, Shenghong; Wang, Xiaoxiao; Wang, Yi; Tian, Yingxuan

doi:10.1042/bsr20193169

Cited by 24 publications

(26 citation statements)

References 12 publications

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“…EMT, a process whereby epithelial cells gradually acquire a mesenchymal identity, is widely recognized to be involved in LUAD metastasis [ 18 ]. Most of the previous studies have focused on the functions and mechanisms of some ERGs [ 19 – 21 ]. However, ERG-based prognostic models have not been previously explored in LUAD.…”

Section: Discussionmentioning

confidence: 99%

Systematic construction and validation of an epithelial–mesenchymal transition risk model to predict prognosis of lung adenocarcinoma

Tang

Jiang

Cheng

et al. 2020

Aging

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Epithelial–mesenchymal transition (EMT) has been shown to be linked to a poor prognosis, particularly in patients with non-small-cell lung cancer. Nevertheless, little is known regarding the existence of EMT-related gene signatures and their prognostic values in lung adenocarcinoma (LUAD). In the current study, we systematically profiled the mRNA expression data of patients with LUAD in The Cancer Genome Atlas and Gene Expression Omnibus databases using a total of 1,184 EMT-related genes. The prognostic values of the EMT-related genes used to develop risk score models for overall survival were determined using LASSO and Cox regression analyses. A prognostic signature that consisted of nine unique EMT-related genes was generated using a training set. A nomogram, incorporating this EMT-related gene signature and clinical features of patients with LUAD, was constructed for potential clinical use. Calibration plots, decision-making curves, and receiver operating characteristic curve analysis showed that this model had a good ability to predict the survival of patients with LUAD. The EMT-associated gene signature and prognostic nomogram established in this study were reliable in predicting the survival of patients with LUAD. Thus, we first identified a novel EMT-related gene signature and developed a nomogram for predicting the prognosis of patients with LUAD.

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Section: Discussionmentioning

confidence: 99%

Systematic construction and validation of an epithelial–mesenchymal transition risk model to predict prognosis of lung adenocarcinoma

Tang

Jiang

Cheng

et al. 2020

Aging

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“…The elevated level of ROS is a salient feature of aggressive cancers like ES [ 49 , 50 ]. STEAP1 expression has been linked to increased cell proliferation, tumorigenicity, metastasis, and invasiveness in various cancers [ 22 , 23 , 24 , 27 ]. Previous studies have shown that STEAP1 overexpression leads to an increase in cytoplasmic and mitochondrial ROS levels in the ES [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

“…It is a 339 amino acid transmembrane protein implicated in cell adhesion, regulation of reactive oxygen species levels, and acts as an ion channel or transporter for cell–cell communication [ 24 ]. STEAP1 expression is highly upregulated in several cancers, including prostate, bladder, pancreas, ovary, gastrointestinal tract, cervix, and testicular cancer, as well as ES [ 25 , 26 , 27 , 28 , 29 ]. In the case of ES, STEAP1 is a direct transcriptional target of EWSFLI1 [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of a New Transcriptional Co-Regulator of STEAP1 in Ewing’s Sarcoma

Markey

Romero

Parashar

et al. 2021

Cells

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Ewing’s sarcoma (ES) is caused by a chromosomal translocation leading to the formation of the fused EWSFLI1 gene, which codes for an aberrant transcription factor EWSFLI1. The transcriptional targets of EWSFLI1 have been viewed as promising and novel drug targets in the treatment of ES. One such target is six transmembrane epithelial antigen of the prostate 1 (STEAP1), a transmembrane protein that is upregulated by EWSFLI1 in ES. STEAP1 is a hallmark of tumor invasiveness and an indicator of tumor responsiveness to therapy. EWSFLI1 binds to the STEAP1 promoter region, but the mechanism of action by which it upregulates STEAP1 expression in ES is not entirely understood. Upon analysis of the STEAP1 promoter, we predicted two binding sites for NKX2.2, another crucial transcription factor involved in ES pathogenesis. We confirmed the interaction of NKX2.2 with the STEAP1 promoter using chromatin immunoprecipitation (ChIP) analysis. We used single-molecule RNA imaging, biochemical, and genetic studies to identify the novel role of NKX2.2 in regulating STEAP1 expression in ES. Our results show that NKX2.2 is a co-regulator of STEAP1 expression and functions by interacting with the STEAP1 promoter at sites proximal to the reported EWSFLI1 sites. The co-operative interaction of NKX2.2 with EWSFLI1 in regulating STEAP1 holds potential as a new target for therapeutic interventions for ES.

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“…In other cancers, the JAK2/STAT3 signaling pathway is also implicated in cancer progression. In lung adenocarcinoma, JAK2/STAT3 pathway is also implicated in EMT and metastasis of cancer cells [55]. In melanoma, the anti-tumor effect of brevilin A also depends on the JAK2/STAT3 pathway [56].…”

Section: Discussionmentioning

confidence: 99%

LINC00893 Inhibits The Progression of Prostate Cancer Through miR-3173-5p/SOCS3/JAK2/STAT3 Pathway

Yu¹,

Fan²,

Liu³

et al. 2021

Preprint

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Background: Prostate cancer (PCa) is one of the most common malignant tumors in the male urinary system. In recent years, the morbidity and mortality of PCa have been increasing due to the limited effects of existing treatment strategies. Long non-coding RNA (lncRNA) LINC00893 inhibits the proliferation and metastasis of papillary thyroid cancer (PTC) cells, but its role in PCa has not been reported. Our study aims to clarify the role and underlying mechanism of LINC00893 in regulating the progression of PCa.Methods: We analyzed LINC00893 expression through TCGA database. We also collected 66 paires of PCa tissues and matched para-cancerous tissues as well as cell lines and assessed LINC00893 expression. Subsequently, we conducted gain-of-function assays to confirm the role of LINC00893 in PCa. CCK-8, EdU, colony information and transwell assays were implemented to detect cell proliferation, colony formation and metastasis abilities, respectively. RT-qPCR and western blot assays were used to quantify the expression of mRNA and protein. Dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP) and RNA pull down assays were conducted to evaluate the interaction of molecules. Spearman correlation coefficient analysis was conducted to detect the correlation between molecules.Results: We found that the LINC00893 expression in PCa tissues and cell lines was upregulated compared with matched controls, and patients with low expression of LINC00893 suffered a low overall survival rate. Overexpression of LINC00893 hindered the proliferation, epithelial-mesenchymal transition (EMT) as well as metastasis of PCa cells in vitro and in vivo. In terms of mechanism, suppressor of cytokine signaling 3 (SOCS3)/Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway occupied a central position in the regulation of PCa progression by LINC00893. LINC00893 weakened the inhibition role of miR-3173-5p on SOCS3 expression through functioning as a miR-3173-5p sponge, which inhibited the JAK2/STAT3 signaling pathway. Conclusions: LINC00893 suppresses the progression of prostate cancer through miR-3173-5p/SOCS3/JAK2/STAT3 pathway. our data uncovers a novel mechanism by which LINC00893 hinders the progression of PCa, which enriches the molecular network of LINC00893 regulating the PCa progression and laies a theoretical foundation for PCa targeted therapy.

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STEAP1 facilitates metastasis and epithelial–mesenchymal transition of lung adenocarcinoma via the JAK2/STAT3 signaling pathway

Cited by 24 publications

References 12 publications

Systematic construction and validation of an epithelial–mesenchymal transition risk model to predict prognosis of lung adenocarcinoma

Systematic construction and validation of an epithelial–mesenchymal transition risk model to predict prognosis of lung adenocarcinoma

Identification of a New Transcriptional Co-Regulator of STEAP1 in Ewing’s Sarcoma

LINC00893 Inhibits The Progression of Prostate Cancer Through miR-3173-5p/SOCS3/JAK2/STAT3 Pathway

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