Homeobox B8 Targets Sterile Alpha Motif Domain-Containing Protein 9 and Drives Glioma Progression

Ma, Wenping; Jin, Hongze; Liu, Wenjie; Li, Xiaojuan; Zhou, Xingang; Guo, Xinwu; Tian, Runfa; Cui, Qi; Luo, Junjie; Jiao, Yueying; Yu, Youtao; Yang, Haifeng; Zhao, Hongshan

doi:10.1007/s12264-019-00436-y

Cited by 13 publications

(16 citation statements)

References 33 publications

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“…The IFN-g binding element is located within the SAMD9 promoter in humans and IFN is the cytokine produced by gliomas, influencing the immune response through TAMs (52,53). We have revealed that knocking down SAMD9 expression levels in glioma cells decreased the glioblastoma cell progression via the AKT/PI3K pathway, but the detailed mechanism of how SAMD9 affected the occurrence of gliomas and its impact on tumor immunity has not been reported in gliomas (29). This is the first report to demonstrate that SAMD9 has a role not only as a significance marker related to malignancy characteristics in glioma, but also may as an independent prognostic indicator in lower grade glioma patients; further study found that SAMD9 influences the immune response by increasing the ability of M2 macrophage to infiltrate in vitro.…”

Section: Discussionmentioning

confidence: 93%

“…After incubation at 37°C for 24 h, the cells in the upper chamber were fixed in 4% formalin and stained with 0.1% crystal violet. The infiltrated M2 macrophage cells were counted in three randomly selected fields from each membrane and each experiment was performed three times (29,(36)(37)(38).…”

Section: M2 Macrophage Infiltration Assaysmentioning

confidence: 99%

“…Deleterious mutations of SAMD9 are key enabling factors for some autoimmune diseases and cancers, as well as the pathogenesis of myelodysplastic syndromes (MDS), esophageal and lung tumorigenesis (29). Our previous studies have shown that knocking down SAMD9 in glioma cells decreases glioblastoma progression (30).…”

Section: Introductionmentioning

confidence: 99%

“…We reveal that elevated SAMD9 expression is closely correlated with increasing WHO grade. Furthermore, knockdown of SAMD9 attenuated the proliferation, migration and invasion of glioblastoma cells and reduced the activity of the PI3K/AKT signaling pathway (29). Till now, the detailed regulatory mechanism of SAMD9 and its impact on tumor immunity in gliomas has not been reported, whether SAMD9 could influence the immune response in gliomas is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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SAMD9 Is Relating With M2 Macrophage and Remarkable Malignancy Characters in Low-Grade Glioma

Zhang

Bao

et al. 2021

Front. Immunol.

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Immunoreactions regulated by TAMs (Tumor-associated macrophages) play a pivotal role in tumorigenesis and metastasis. In recent decades, treatments based on immune regulation have achieved revolutionary breakthroughs in cancer targeted therapies. The phenotypes of TAMs in gliomas are more heterogeneous and inherently complex than can be simply defined by classification into the M1 and M2 polarized states. The detailed mechanisms surrounding infiltrating macrophage phenotype and glioma characteristics remain undefined. SAMD9 (Sterile Alpha Motif Domain-Containing Protein 9) was found to be highly expressed in glioma and closely related to histological and genetic features in CGGA and TCGA databases. Simultaneously, we present evidence to show that there was a positive association between SAMD9 and malignancy characters in LGG. Univariable and Multivariate proportional hazard Cox analysis showed that SAMD9 was an independent prognostic factor for LGG. Surprisingly, Gene Ontology (GO) analysis showed SAMD9 expression level was remarkably well correlated with immunological responses and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis supported the connection with immune responses and tumorigenesis. Immune infiltration analysis demonstrated that high SAMD9 expression resulted in an accumulation of macrophages by CIBERSORT and TIMER databases, especially positively related to macrophage total marker gene AIF1 and Macrophage M2 marker gene CD163. IHC staining further indicated a high correlation of SAMD9 with those specific macrophage markers in the immune response. Human THP-1 cells were induced into M2 macrophages, which were then co-cultured with LN229 cells. Silencing of SAMD9 by shRNA in LN229 cells attenuated the infiltration abilities of M2 macrophage. SAMD9 explored immune response via relating of M2 macrophage in vitro. Our results revealed SAMD9 acted as the malignancy characters in LGG, enrichment with M2 macrophage.

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Section: Discussionmentioning

confidence: 93%

Section: M2 Macrophage Infiltration Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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SAMD9 Is Relating With M2 Macrophage and Remarkable Malignancy Characters in Low-Grade Glioma

Zhang

Bao

et al. 2021

Front. Immunol.

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“…RSF1 regulates H2Aub-mediated gene silencing, including the classical PRC1 target genes HOXB8 , HOXB7 and HOXC6 [ 22 ]. The increased expression of HOXB8 is associated with colorectal cancer [ 27 ], gastric cancer [ 28 ], pancreatic cancer [ 29 ] and GBM [ 30 ]. Increased expression of HOXB7 is associated with colorectal cancer [ 31 ], gastric cancer [ 32 ] and prostate cancer [ 33 ].…”

Section: Rsf1 Interacts With H2aub To Suppress Oncogene Transcriptionmentioning

confidence: 99%

RSF1 in cancer: interactions and functions

2021

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RSF1, remodelling and spacing factor 1, is an important interphase centromere protein and is overexpressed in many types of cancers and correlated with poor overall survival. RSF1 has functions mainly in maintaining chromosome stability, facilitating DNA repair, maintaining the protein homeostasis of RSF1 and suppressing the transcription of some oncogenes when RSF1 protein is expressed at an optimal level; however, RSF1 overexpression facilitates drug resistance and cell cycle checkpoint inhibition to prompt cancer proliferation and survival. The RSF1 expression level and gene background are crucial for RSF1 functions, which may explain why RSF1 has different functions in different cancer types. This review summarizes the functional domains of RSF1, the overexpression status of RSF1 and SNF2H in cancer based on the TCGA and GTEX databases, the cancer-related functions of RSF1 in interacting with H2Aub, HDAC1, CENP-A, PLK1, ATM, CENP-S, SNF2H, HBX, BubR1, cyclin E1, CBP and NF-κB and the potential clinical value of RSF1, which will lay a theoretical foundation for the structural biology study of RSF1 and application of RSF1 inhibitors, truncated RSF1 proteins and SNF2H inhibitors in the treatment of RSF1-overexpressing tumours.

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SAMD9 Promotes Postoperative Recurrence of Esophageal Squamous Cell Carcinoma by Stimulating MYH9‐Mediated GSK3β/β‐Catenin Signaling

et al. 2023

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Recurrence is a challenge to survival after the initial treatment of esophageal squamous cell carcinoma (ESCC). But, its mechanism remains elusive and there are currently no biomarkers to predict postoperative recurrence. Here, the possibility of sterile alpha motif domain‐containing protein 9 (SAMD9) as a predictor of postoperative recurrence of ESCC is evaluated and the molecular mechanisms by which SAMD9 promotes ESCC recurrence are elucidated. The authors found that the high level of SAMD9 is correlated with postoperative recurrence and poor prognosis of ESCC. Overexpression of SAMD9 promotes tumor stemness, angiogenesis, and EMT, while downregulation of SAMD9 reduced these phenotypes. Mechanistically, it is found that SAMD9 stimulated ubiquitination‐mediated glycogen synthase kinase‐3 beta (GSK‐3β) degradation by interaction with myosin‐9 (MYH9) and TNF receptor‐associated factor 6 (TRAF6), which in turn activated Wnt/β‐catenin pathway. Further, the authors demonstrated that silencing SAMD9 inhibited lung metastasis and tumor formation in vivo. Finally, the authors found that silencing MYH9 or β‐catenin, or overexpressing GSK‐3β inhibited SAMD9‐stimulated ESCC cell stemness, EMT, angiogenesis, metastasis, and tumorigenicity. Together, the findings indicate that the SAMD9/MYH9/GSK3β/β‐catenin axis promotes ESCC postoperative recurrence and that SAMD9 is a crucial target for ESCC therapy. Additionally, SAMD9 has the potential as a predictor of postoperative recurrence in ESCC.

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Homeobox B8 Targets Sterile Alpha Motif Domain-Containing Protein 9 and Drives Glioma Progression

Cited by 13 publications

References 33 publications

SAMD9 Is Relating With M2 Macrophage and Remarkable Malignancy Characters in Low-Grade Glioma

SAMD9 Is Relating With M2 Macrophage and Remarkable Malignancy Characters in Low-Grade Glioma

RSF1 in cancer: interactions and functions

SAMD9 Promotes Postoperative Recurrence of Esophageal Squamous Cell Carcinoma by Stimulating MYH9‐Mediated GSK3β/β‐Catenin Signaling

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