Long noncoding RNA NR2F1-AS1 plays a carcinogenic role in gastric cancer by recruiting transcriptional factor SPI1 to upregulate ST8SIA1 expression

Zuo, Fang; Zhang, Yong; Li, Jianting; Yang, Shao-Xiang; Chen, Xiaolu

doi:10.1080/21655979.2021.2001168

Cited by 16 publications

(11 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we found that SPI1 is an important regulator of MES phenotype transition and maintenance in GSCs. Similarly, previous studies have shown the potential role of SPI1 in the MES transition in gastric cancer [18], colorectal cancer [19], and non-small-cell lung cancer [16]. This underscores the recognized correlation between MES transition, stemness acquisition, invasiveness, treatment resistance, and metastasis.…”

Section: Fkbp12 Plays a Regulatory Role In Spi1-induced Tgf-β1-pi3k-a...supporting

confidence: 77%

SPI1 activates TGF‐β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12 to support the mesenchymal phenotype of glioma stem cells

Song,

Zhang,

Wang

et al. 2023

Brain Pathology

View full text Add to dashboard Cite

Glioma stem cells (GSCs) exhibit diverse molecular subtypes with the mesenchymal (MES) population representing the most malignant variant. The oncogenic potential of Salmonella pathogenicity island 1 (SPI1), an oncogenic transcription factor, has been established across various human malignancies. In this study, we explored the association between the SPI1 pathway and the MES GSC phenotype. Through comprehensive analysis of the Cancer Genome Atlas and Chinese Glioma Genome Atlas glioma databases, along with patient‐derived GSC cultures, we analyzed SPI1 expression. Using genetic knockdown and overexpression techniques, we assessed the functional impact of SPI1 on GSC MES marker expression, invasion, proliferation, self‐renewal, and sensitivity to radiation in vitro, as well as its influence on tumor formation in vivo. Additionally, we investigated the downstream signaling cascades activated by SPI1. Our findings revealed a positive correlation between elevated SPI1 expression and the MES phenotype, which in turn, correlated with poor survival. SPI1 enhanced GSC MES differentiation, self‐renewal, and radioresistance in vitro, promoting tumorigenicity in vivo. Mechanistically, SPI1 augmented the transcriptional activity of both TGF‐β1 and FKBP12 while activating the non‐canonical PI3K/Akt pathway. Notably, inhibition of TGF‐β1/PI3K/Akt signaling partially attenuated SPI1‐induced GSC MES differentiation and its associated malignant phenotype. Collectively, our results underscore SPI1's role in activating TGF‐β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12, thereby supporting the aggressive MES phenotype of GSCs. Therefore, SPI1 emerges as a potential therapeutic target in glioma treatment.

show abstract

Section: Fkbp12 Plays a Regulatory Role In Spi1-induced Tgf-β1-pi3k-a...supporting

confidence: 77%

SPI1 activates TGF‐β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12 to support the mesenchymal phenotype of glioma stem cells

Song,

Zhang,

Wang

et al. 2023

Brain Pathology

View full text Add to dashboard Cite

show abstract

“…However, the specific mechanism needs further research and verification. Previous studies found that NR2F1-AS1 upregulates the expression level of ST8SIA1 by recruiting SPI1, thereby promoting proliferation and metastasis of BCa cells ( 33 ). LINC00649 has verified its tumor-promoting effect in gastric cancer, colorectal cancer, BCa, etc ( 34 – 36 ).…”

Section: Discussionmentioning

confidence: 97%

Prognostic significance and identification of basement membrane-associated lncRNA in bladder cancer

et al. 2022

View full text Add to dashboard Cite

Based on the importance of basement membrane (BM) in cancer invasion and metastasis, we constructed a BM-associated lncRNA risk model to group bladder cancer (BCa) patients. Transcriptional and clinical data of BCa patients were downloaded from The Cancer Genome Atlas (TCGA), and the expressed genes of BM-related proteins were obtained from the BM-BASE database. We download the GSE133624 chip data from the GEO database as an external validation dataset. We screened for statistically different BM genes between tumors and adjacent normal tissues. Co-expression analysis of lncRNAs and differentially expressed BM genes was performed to identify BM-related lncRNAs. Then, differentially expressed BM-related lncRNAs (DEBMlncRNAs) between tumor and normal tissues were identified. Univariate/multivariate Cox regression analysis was performed to select lncRNAs for risk assessment. LASSO analysis was performed to build a prognostic model. We constructed a model containing 8 DEBMlncRNAs (AC004034.1, AL662797.1, NR2F1-AS1, SETBP1-DT, AC011503.2, AC093010.2, LINC00649 and LINC02321). The prognostic risk model accurately predicted the prognosis of BCa patients and revealed that tumor aggressiveness and distant metastasis were associated with higher risk scores. In this model, we constructed a nomogram to assist clinical decision-making based on clinicopathological characteristics such as age, T, and N. The model also showed good predictive power for the tumor microenvironment and mutational burden. We validated the expression of eight lncRNAs using the dataset GSE133624 and two human bladder cancer cell lines (5637, BIU-87) and examined the expression and cellular localization of LINC00649 and AC011503.2 using a human bladder cancer tissue chip. We found that knockdown of LINC00649 expression in 5637 cells promoted the proliferation of 5637 cells.Our eight DEBMlncRNA risk models provide new insights into predicting prognosis, tumor invasion, and metastasis in BCa patients.

show abstract

“…Coincidentally, upregulation of SPI1 has been reported in ESCC and correlated with M2 macrophage maintenance [ 37 ]. The transcription regulation of SPI1 on the downstream targets in several cancer cases has been reported to involve lncRNAs [ 26 , 27 ]. The lncRNAs are over 200-nt noncoding RNAs fulfilling key functions in governing chromatin dynamics, gene expression, growth, differentiation, and development of cancer [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…Intriguingly, the regulation of SPI1 on the transcription of molecular substrates in several cancer cases has been reported to involve lncRNAs [ 26 , 27 ]. We wondered if any lncRNA holds accountable for the SPI1-mediated SIGLEC9 activation in TAMs.…”

Section: Radiotherapy Induces Phenotype Change Of Tamsmentioning

confidence: 99%

LINC01004-SPI1 axis-activated SIGLEC9 in tumor-associated macrophages induces radioresistance and the formation of immunosuppressive tumor microenvironment in esophageal squamous cell carcinoma

Zhao

Tian

Wang

et al. 2023

Cancer Immunol Immunother

View full text Add to dashboard Cite

Radioresistance and immunosuppression remain the major obstacles in the anti-cancer treatments. This work studies the functions of sialic acid binding Ig like lectin 9 (SIGLEC9) and its related molecules in radioresistance and immunosuppression in esophageal squamous cell carcinoma (ESCC). The single-cell analysis showed that SIGLEC9 was mainly expressed on tumor-associated macrophages (TAMs). Monocytes-derived macrophages were co-cultured with ESCC cells and subjected to radiotherapy. High or low doses of radiotherapy induced SIGLEC9 upregulation and M2 polarization of TAMs. Artificial inhibition of SIGLEC9 in TAMs suppressed the radioresistance and immunosuppressive tumor microenvironment (TME) in the co-cultured ESCC cells. Upstream molecules of SIGLEC9 were predicted via bioinformatics. LINC01004 recruited Spi-1 proto-oncogene (SPI1) in nucleus of TAMs to induce transcriptional activation of SIGLEC9. SIGLEC9 interacted with mucin 1 (MUC1). MUC1 overexpression in ESCCs induced M2 skewing of TAMs, enhanced radioresistance and immunosuppression, and promoted nuclear translocation of β-catenin to suppress radiotherapy-induced ferroptosis of ESCC cells. These effects were blocked upon SIGLEC9 suppression. In vitro results were reproduced in the animal models with xenograft tumors. Taken together, this study demonstrates that the LINC01004-SPI1 axis-activated SIGLEC9 in TAMs induces radioresistance and the formation of immunosuppressive TME in ESCC.

show abstract

Long noncoding RNA NR2F1-AS1 plays a carcinogenic role in gastric cancer by recruiting transcriptional factor SPI1 to upregulate ST8SIA1 expression

Cited by 16 publications

References 28 publications

SPI1 activates TGF‐β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12 to support the mesenchymal phenotype of glioma stem cells

SPI1 activates TGF‐β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12 to support the mesenchymal phenotype of glioma stem cells

Prognostic significance and identification of basement membrane-associated lncRNA in bladder cancer

LINC01004-SPI1 axis-activated SIGLEC9 in tumor-associated macrophages induces radioresistance and the formation of immunosuppressive tumor microenvironment in esophageal squamous cell carcinoma

Contact Info

Product

Resources

About