Synaptopodin-2 promotes hepatocellular carcinoma metastasis via calcineurin-induced nuclear-cytoplasmic translocation

Gao, Jie; Zhang, Huapeng; Sun, Yaohui; Guo, Wenzhi; Li, Jie; Tang, Hongwei; Guo, Dongyun; Zhang, Jiakai; Shi, Xiaohong; Yu, Dongsheng; Zhang, Xiaodan; Shi, Jiahua; Zhang, Shuijun

doi:10.1016/j.canlet.2020.04.005

Cited by 17 publications

(14 citation statements)

References 31 publications

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“…SYNPO2 is a gene that encodes for the syntrophin‐2 protein, which plays an important role on the cell membrane. Recent studies have shown that the expression of SYNPO2 is closely related to the proliferation, migration, and invasion of cancer cells in a variety of tumours 20,21 . Through immunohistochemistry, we found that SYNPO2 is mainly expressed in the tumour cells, fibroblasts, inflammatory cell (eosinophils and lymphocytes) in gastric cancer tissue.…”

Section: Resultsmentioning

confidence: 62%

“…Recent studies have shown that the expression of SYNPO2 is closely related to the proliferation, migration, and invasion of cancer cells in a variety of tumours. 20,21 Through immunohistochemistry, we found that SYNPO2 is mainly expressed in the tumour cells, fibroblasts, inflammatory cell (eosinophils and lymphocytes) in gastric cancer tissue. However, SYNPO2 is expressed at nearly undetectable levels in the stromal cells of normal gastric mucosa (Figure 7).…”

Section: Synpo2 Is An Important Gene For Predicting Gcpmmentioning

confidence: 91%

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Gastric cancer peritoneal metastasis related signature predicts prognosis and sensitivity to immunotherapy in gastric cancer

Sun,

Chen,

Zhuang

et al. 2023

J Cellular Molecular Medi

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Gastric cancer peritoneal metastases (GCPM) is a leading cause of GC‐related death. Early detection of GCPM is critical for improving the prognosis of advanced GC. Differentially expressed genes (DEGs) were identified in the GSE62254 database to distinguish between GCPM and non‐GCPM. The gastric cancer peritoneal metastases signature (GCPMs) was developed using DEGs. We analysed the effectiveness of GCPMs as indicators for prognosis, chemotherapy, and immune therapy response in GC patients. Subsequently, we analysed the correlation between GCPMs and immune microenvironment as well as immune escape in GC patients. Random forest model and immunohistochemistry was utilized to identify the crucial genes that can aid in the diagnosis of GCPM. We identified five DEGs and utilized their expression to construct GCPMs. Patients with high GCPMs had a higher likelihood of a poor prognosis, while those with low GCPMs appeared to potentially benefit more from chemotherapy. GCPMs were a dependable marker for predicting the response to immunotherapy. Additionally, GCPMs was found to be significantly linked to stromal score and cancer‐associated fibroblasts. SYNPO2 has been identified as the gene with the highest significance in the diagnosis of GCPM. Immunohistochemistry suggests that SYNPO2‐positive expression in tumour cells, fibroblasts, inflammatory cell may be associated with promoting peritoneal metastasis in GC. GCPMs have shown to be a promising biomarker for predicting the prognosis and response of GC patients to chemotherapy and immunotherapy. The use of GCPMs for individual tumour evaluation may pave the way for personalized treatment for GC patients in the future.

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Section: Resultsmentioning

confidence: 62%

Section: Synpo2 Is An Important Gene For Predicting Gcpmmentioning

confidence: 91%

Gastric cancer peritoneal metastasis related signature predicts prognosis and sensitivity to immunotherapy in gastric cancer

Sun,

Chen,

Zhuang

et al. 2023

J Cellular Molecular Medi

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“…Then functional enrichment analyses were performed using the genes positively correlated with SCG2. The results suggested that SCG2 was strongly correlated with MYH11, SYNPO2, DDR2, FABP4, and TNS1, which were all involved in tumorigenesis and inflammatory immune response ( Gan et al, 2019 ; Gao et al, 2020 ; Liu et al, 2020 ; Matrai et al, 2020 ; Sun et al, 2020 ; Tian et al, 2020 ). Higher expression of these genes might associate with worse survival and higher clinical stage of CRC patients.…”

Section: Discussionmentioning

confidence: 98%

SCG2 is a Prognostic Biomarker Associated With Immune Infiltration and Macrophage Polarization in Colorectal Cancer

Wang

Yin

Hong

et al. 2022

Front. Cell Dev. Biol.

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Colorectal cancer (CRC) is the second most lethal malignancy around the world. Limited efficacy of immunotherapy creates an urgent need for development of novel treatment targets. Secretogranin II (SCG2) is a member of the chromogranin family of acidic secretory proteins, has a role in tumor microenvironment (TME) of lung adenocarcinoma and bladder cancer. Besides, SCG2 is a stroma-related gene in CRC, its potential function in regulating tumor immune infiltration of CRC needs to be fully elucidated. In this study, we used western blot, real-time PCR, immunofluorescence and public databases to evaluate SCG2 expression levels and distribution. Survival analysis and functional enrichment analysis were performed. We examined TME and tumor infiltrating immune cells using ESTIMATE and CIBERSORT algorithm. The results showed that SCG2 expression was significantly decreased in CRC tumor tissues, and differentially distributed between tumor and adjacent normal tissues. SCG2 was an independent prognostic predictor in CRC. High expression of SCG2 correlated with poor survival and advanced clinical stage in CRC patients. SCG2 might regulate multiple tumor- and immune-related pathways in CRC, influence tumor immunity by regulating infiltration of immune cells and macrophage polarization in CRC.

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“…Lower expression of SYNPO2 was found to significantly increase the levels of phosphorylation of PI3K/AKT which activates the PI3K/AKT pathway to promote breast cancer and associated with the poor prognosis of the patients [ 70 ]. Reduced SYNPO2 increase the aggressiveness of Hepatocellular Carcinoma and melanoma which significantly lower the survival rate of the patients [ 71 , 72 ]. The activation of PI3K/AKT directly induce the EMT pathway [ 73 ].…”

Section: Discussionmentioning

confidence: 99%

“…Hence, it can be postulated that the lower expression of SYNPO2 significantly associated with poor prognosis of both CRC and CC and could function as prognostic biomarker. SYNPO2 was demonstrated as a prognostic and therapeutic biomarker for melanoma, hepatocellular carcinoma, breast cancer, and bladder cancer [ 70 , 71 , 72 , 75 ]. Moreover, NFE2L2, TP63, RUNX1, SOX2, MITF, PPARG, OLIG2, SMARCA4, ATF3, YY1, SUZ12, BACH1, CEBPA and CEBPB sequence-specific DNA-binding factors were identified for SYNPO2 which may regulate the expression level of SYNPO2 by suppressing or activating the transcription.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs expression analysis shows key affirmation of Synaptopodin-2 as a novel prognostic and therapeutic biomarker for colorectal and cervical cancers

Hossain

Tonmoy

Islam

et al. 2021

Heliyon

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MicroRNAs play a crucial role in tumorigenesis, tumor progression, and metastasis, and thus they contribute in development of different malignancies including cervical cancer (CC) and colorectal cancer (CRC). Through integrated strategies of computational biology, this study aims to identify prognostic biomarkers responsible for CRC and CC prognosis, and potential therapeutic agents to halt the progression of these cancers. Expression analysis of miRNA datasets of CRC and CC identified 17 differentially expressed miRNAs (DEMs). SYNPO2, NEGR1, FGF7, LIFR, RUNX1T1, CFL2, BNC2, EPHB2, PMAIP1, and CDC25A differentially expressed genes (DEGs) regulated by these DEMs were classified as candidate genes responsible for CRC and CC. Down-regulation of Synaptopodin-2 (SYNPO2) is involved in emergence and progression of these cancers by activating ER, PI3K/AKT, and EMT pathways as well as by suppressing DNA damage response, and cell cycle pathways. Higher methylation rate in promoter region of SYNPO2 could be a possible reason for lowering the expression of SYNPO2 in tumor stages. Hence, the lower expression of SYNPO2 is associated with poor prognosis of CRC and CC and could function as prognostic biomarker and therapeutic target. Fourteen transcription factors were recognized which can activate/inhibit the transcription of SYNPO2 and may be a potential target to regulate expression of SYNPO2 in CRC and CC. Retinoic acid and Estradiol were identified as putative therapeutic drugs for CRC and CC patients. This study will thus help in understanding the underlying molecular events in CRC and CC that may improve the detection of malignant lesions in primary screening and will broaden the clinical applications.

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Synaptopodin-2 promotes hepatocellular carcinoma metastasis via calcineurin-induced nuclear-cytoplasmic translocation

Cited by 17 publications

References 31 publications

Gastric cancer peritoneal metastasis related signature predicts prognosis and sensitivity to immunotherapy in gastric cancer

Gastric cancer peritoneal metastasis related signature predicts prognosis and sensitivity to immunotherapy in gastric cancer

SCG2 is a Prognostic Biomarker Associated With Immune Infiltration and Macrophage Polarization in Colorectal Cancer

MicroRNAs expression analysis shows key affirmation of Synaptopodin-2 as a novel prognostic and therapeutic biomarker for colorectal and cervical cancers

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