The role of septin 7 in physiology and pathological disease: A systematic review of current status

Wang, Xinlu; Fei, Fei; Qu, Jie; Li, Chunyuan; Li, Yuwei; Zhang, Shiwu

doi:10.1111/jcmm.13623

Cited by 31 publications

(32 citation statements)

References 114 publications

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“…It is well known that septins are implicated in the development of various diseases. Septin 7 is linked to Alzheimer’s disease, schizophrenia, neuropsychiatric erythematosus lupus and different tumors [27]. Nevertheless targeting septins still is a rather neglected research topic.…”

Section: Discussionmentioning

confidence: 99%

The phytohormone forchlorfenuron decreases viability and proliferation of malignant mesothelioma cells in vitro and in vivo

et al. 2019

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Malignant mesothelioma (MM) is one of the most aggressive cancer types with a patient’s life expectancy of typically less than one year upon diagnosis. The urgency of finding novel therapeutic approaches to treat mesothelioma is evident. Here we tested the effect of the plant-growth regulator forchlorfenuron (FCF), an inhibitor of septin function(s) in mammalian cells, on the viability and proliferation of MM cell lines, as well as other tumor cell lines derived from lung, prostate, colon, ovary, cervix and breast. Exposure to FCF strongly inhibited proliferation of human and mouse (most efficiently epithelioid) MM cells and all other tumor cells in a concentration-dependent manner and led to cell cycle arrest and cell death. The role of septin 7 (SEPT7), a presumably essential target of FCF in MM cells was confirmed by an shRNA strategy. FCF was robustly inhibiting tumor cell growth in vitro at low micromolar (IC50: ≈20-60µM) concentrations and more promisingly also in vivo. Initial experiments with FCF analogous revealed the importance of FCF’s chloride group for efficient cell growth inhibition. FCF’s rather low systemic toxicity might warrant for an extended search for other related and possibly more potent FCF analogues to target MM and putatively other septin-dependent tumors.

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Section: Discussionmentioning

confidence: 99%

The phytohormone forchlorfenuron decreases viability and proliferation of malignant mesothelioma cells in vitro and in vivo

et al. 2019

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“…SEPT7 is also implicated in several types of cancer 18 – 20 . While the septin family plays a critical role in cytokinesis 21 , SEPT7 is also involved in the cytoskeleton and participates in regulation of cytokinesis 22 , 23 . Septin-deficient T cells fail to complete cytokinesis when prompted by pharmacological activation or cytokines.…”

Section: Discussionmentioning

confidence: 99%

A multi-omics study links TNS3 and SEPT7 to long-term former smoking NSCLC survival

Shen

Wei

et al. 2021

npj Precis. Onc.

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The genetic architecture of non-small cell lung cancer (NSCLC) is relevant to smoking status. However, the genetic contribution of long-term smoking cessation to the prognosis of NSCLC patients remains largely unknown. We conducted a genome-wide association study primarily on the prognosis of 1299 NSCLC patients of long-term former smokers from independent discovery (n = 566) and validation (n = 733) sets, and used in-silico function prediction and multi-omics analysis to identify single nucleotide polymorphisms (SNPs) on prognostics with NSCLC. We further detected SNPs with at least moderate association strength on survival within each group of never, short-term former, long-term former, and current smokers, and compared their genetic similarity at the SNP, gene, expression quantitative trait loci (eQTL), enhancer, and pathway levels. We identified two SNPs, rs34211819TNS3 at 7p12.3 (P = 3.90 × 10−9) and rs1143149SEPT7 at 7p14.2 (P = 9.75 × 10−9), were significantly associated with survival of NSCLC patients who were long-term former smokers. Both SNPs had significant interaction effects with years of smoking cessation (rs34211819TNS3: Pinteraction = 8.0 × 10−4; rs1143149SEPT7: Pinteraction = 0.003). In addition, in silico function prediction and multi-omics analysis provided evidence that these QTLs were associated with survival. Moreover, comparison analysis found higher genetic similarity between long-term former smokers and never-smokers, compared to short-term former smokers or current smokers. Pathway enrichment analysis indicated a unique pattern among long-term former smokers that was related to immune pathways. This study provides important insights into the genetic architecture associated with long-term former smoking NSCLC.

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“…As for the systemic lupus erythematosus, more studies are needed to investigate its relationship with glioma [13]. IDH mutation can promote leukemogenesis, and hematopoietic cell lineage was suggested in gliomas in previous studies [14][15][16][17]. However, whether glioma patient with these diseases has a short OS and the underlying mechanisms require further studies.…”

Section: Discussionmentioning

confidence: 99%

Survival Risk Prediction Models of Gliomas Based on IDH and 1p/19q

et al. 2020

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Gliomas have been classified into different molecular subtypes based on their molecular features. To explore the prognostic factors of different subtypes of gliomas, we performed a univariate survival analysis based on the RNA-seq data of 653 patients obtained from The Cancer Genome Atlas. We identified 12205 (20.18%), 6125 (10.13%) and 5206 (8.61%) genes associated with the overall survival (OS) of the IDH-wildtype, IDH-mutation 1p/19q intact and IDH-mutation 1p/19q codeletion gliomas, respectively. Pathway enrichment analysis revealed that OS related genes were mainly involved in alcoholism, systemic lupus erythematosus, hematopoietic cell lineage and diabetes. The OS related genes were further selected using Lasso regression, and three prognostic risk score models were constructed to effectively predict the OS of the patients with different subtypes of gliomas. In total, 76 signature genes were identified and were selected to construct the three models. Moreover, neither of the 76 genes overlapped between different models, which suggested the enormous difference among the three subtypes, although some signature genes (SERPINA5, RP11.229A12.2 and RP11.62F24.2) were also identified as the OS related genes in different glioma subtypes. Interestingly, five genes (RP11.229A12.2, RP11.62F24.2, C3orf67, RP11.275H4.1 and TBX3) played opposing roles (protective or risk factor) in different subtypes. Additionally, the prognosis models consisted of a substantial proportion of non-coding RNA (58.74%, 70.13% and 58.11% in the IDH-wildtype, IDH-mutation 1p/19q intact and IDH-mutation 1p/19q codeletion). Furthermore, multivariate analysis integrating clinical variables demonstrated that risk group predicted by the prognostic models was an independent prognostic factor for gliomas. In conclusion, we have constructed and validated three models that have the potential to predict the prognosis of glioma patients. The genes and pathways identified in this study require further investigation for their underlying mechanisms and potential clinical significance in improving the OS of the glioma patients.

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The role of septin 7 in physiology and pathological disease: A systematic review of current status

Cited by 31 publications

References 114 publications

The phytohormone forchlorfenuron decreases viability and proliferation of malignant mesothelioma cells in vitro and in vivo

The phytohormone forchlorfenuron decreases viability and proliferation of malignant mesothelioma cells in vitro and in vivo

A multi-omics study links TNS3 and SEPT7 to long-term former smoking NSCLC survival

Survival Risk Prediction Models of Gliomas Based on IDH and 1p/19q

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