MYC Enhances Cholesterol Biosynthesis and Supports Cell Proliferation Through SQLE

Yang, Fan; Kou, Junjie; Liu, Zizhao; Li, Wei; Du, Wenjing

doi:10.3389/fcell.2021.655889

Cited by 18 publications

(14 citation statements)

References 34 publications

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“…The gene SQLE encodes squalene epoxidase, which is one of the key enzymes and catalyzes the oxidation of squalene to 2,3-oxidosqualene. It is well known that cholesterol is critical to the growth and migration of tumor cells and maintaining optimal levels of cholesterol is requisite for cellular function and viability [4]. Several studies have illustrated that SQLE could promote tumor progression via synthesis of cholesterol [5,6].…”

Section: Ivyspringmentioning

confidence: 99%

Upregulation of SQLE Contributes to Poor Survival in Head and Neck Squamous Cell Carcinoma

Li¹,

Yang²,

Wang³

et al. 2022

Int. J. Biol. Sci.

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Recently, increasing attention has been paid to the role of Squalene epoxidase (SQLE) in several types of cancers. However, its functional role in tumor progression of head and neck squamous cell carcinoma (HNSCC) is still unclear. We performed bioinformatic analyses and relative experiments to assess the potential mechanism of SQLE-mediated HNSCC malignancy. And the results showed that SQLE was significantly upregulated in tumor samples compared with peritumor samples. Mechanistically, miR-584-5p downregulation may lead to the upregulation of SQLE in HNSCC. Moreover, high SQLE expression in HNSCC was associated with TNM stage, distant metastasis, and poor survival, indicating that SQLE be involved in the progression of HNSCC. Furtherly, SQLE boosted proliferation, migration, invasion of HNSCC cells in vitro and in vivo. Bioinformatic studies showed that PI3K/Akt signaling participated in HNSCC progression mediated by SQLE overexpression, which is confirmed by in vitro and in vivo analysis. Particularly, treatment with terbinafine, an inhibitor of SQLE widely used in the treatment of fungal infections, showed a therapeutic influence on HNSCC. Our findings demonstrate that SQLE plays a vital role in HNSCC progression, providing research evidence for SQLE as a prospective HNSCC therapeutic target and for terbinafine as a candidate drug of HNSCC treatment in the future

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Section: Ivyspringmentioning

confidence: 99%

Upregulation of SQLE Contributes to Poor Survival in Head and Neck Squamous Cell Carcinoma

Li¹,

Yang²,

Wang³

et al. 2022

Int. J. Biol. Sci.

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“…Sterols are essential cell membrane components and transporters in many biofilms [60]. SQLE (squalene epoxidase) is rate limiting and the first oxygenation enzyme in cholesterol synthesis [61]. Lanosterol, especially cholesterol, is the upstream precursor of sterol biosynthesis in fungal steroids and animals [62].…”

Section: Degs Involved In Steroid Biosynthesis and Lipid Metabolismmentioning

confidence: 99%

RNA Sequencing Analysis Reveals Divergent Adaptive Response to Hypo- and Hyper-Salinity in Greater Amberjack (Seriola dumerili) Juveniles

Peng

Shi

Liu

et al. 2022

Animals

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Salinity significantly affects physiological and metabolic activities, breeding, development, survival, and growth of marine fish. The greater amberjack (Seriola dumerili) is a fast-growing species that has immensely contributed to global aquaculture diversification. However, the tolerance, adaptation, and molecular responses of greater amberjack to salinity are unclear. This study reared greater amberjack juveniles under different salinity stresses (40, 30, 20, and 10 ppt) for 30 days to assess their tolerance, adaptation, and molecular responses to salinity. RNA sequencing analysis of gill tissue was used to identify genes and biological processes involved in greater amberjack response to salinity stress at 40, 30, and 20 ppt. Eighteen differentially expressed genes (DEGs) (nine upregulated and nine downregulated) were identified in the 40 vs. 30 ppt group. Moreover, 417 DEGs (205 up-regulated and 212 down-regulated) were identified in the 20 vs. 30 ppt group. qPCR and transcriptomic analysis indicated that salinity stress affected the expression of genes involved in steroid biosynthesis (ebp, sqle, lss, dhcr7, dhcr24, and cyp51a1), lipid metabolism (msmo1, nsdhl, ogdh, and edar), ion transporters (slc25a48, slc37a4, slc44a4, and apq4), and immune response (wnt4 and tlr5). Furthermore, KEGG pathway enrichment analysis showed that the DEGs were enriched in steroid biosynthesis, lipids metabolism, cytokine–cytokine receptor interaction, tryptophan metabolism, and insulin signaling pathway. Therefore, this study provides insights into the molecular mechanisms of marine fish adaptation to salinity.

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“…Recently, numerous studies have underlined the role of cholesterol metabolism in the tumorigenesis. Cholesterol metabolism regulates oncogenic signaling pathways, including the 12 Disease Markers PTEN/AKT/mTORC1 [35][36][37], MYC [38], Wnt [39], MAPK [40], and Hippo pathway [41]. Rinks et al [42] reduced cellular cholesterol by blocking the high-density lipoprotein nanoparticles (HDL NP), which can also block the enhanced BCR signaling.…”

Section: Discussionmentioning

confidence: 99%

Identification of CXCR4 Upregulation in Diffuse Large B-Cell Lymphoma Associated with Prognostic Significance and Clinicopathological Characteristics

et al. 2022

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Background. Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignant lymphoma with distinct characteristics. Patients with treatment failure after the standard immunochemotherapy have worse prognosis, which implies the necessity to uncover novel targets. The C-X-C chemokine receptor 4 (CXCR4) overexpression has been identified in several hematopoietic malignancies. However, the expression signatures and prognostic significance of CXCR4 in DLBCL associated with clinicopathological features remain unclear. Methods. Gene expression profiles of DLBCL were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Then, a meta-analysis with an integrated bioinformatic analysis was performed to assess the relationship between CXCR4 expression and clinicopathological features of DLBCL. Finally, experimental verification including immunohistochemical (IHC) staining and real-time quantitative PCR (qPCR) was carried out using patient samples. In vitro cell line viability tests were conducted using CXCR4 inhibitor WZ811. Results. DLBCL patients with activated B-cell-like (ABC) subtype have higher expression level of CXCR4 with worse survival. Differential expressed genes in the CXCR4-upregulation group were enriched in canonical pathways associated with oncogenesis. DLBCL with CXCR4 upregulation had lower degree of CD8+ T cell infiltration. TIMER analysis demonstrated that the CXCR4 expression was positively correlated with the expression of CD5, MYC, NOTCH1, PDCD1, CD274, mTOR, FOXO1, and hnRNPA2B1 in DLBCL. IHC study in patient samples showed the positive correlation between CXCR4 and nongerminal center B-cell (non-GCB) subtype and mTOR expression. Meanwhile, quantitative polymerase chain reaction results revealed that high CXCR4 mRNA level was correlated to double-hit DLBCL. Finally, cell viability test showed that WZ811 exerted antiproliferation effect in DLBCL cell lines in a dose-dependent manner. Conclusion. CXCR4 was upregulated in ABC-DLBCL associated with worse prognosis. Our analysis predicted CXCR4 as a potential target for DLBCL treatment, which may serve as an inhibitor both on BCR signaling and nuclear export warranting further investigation in clinical trials.

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MYC Enhances Cholesterol Biosynthesis and Supports Cell Proliferation Through SQLE

Cited by 18 publications

References 34 publications

Upregulation of SQLE Contributes to Poor Survival in Head and Neck Squamous Cell Carcinoma

Upregulation of SQLE Contributes to Poor Survival in Head and Neck Squamous Cell Carcinoma

RNA Sequencing Analysis Reveals Divergent Adaptive Response to Hypo- and Hyper-Salinity in Greater Amberjack (Seriola dumerili) Juveniles

Identification of CXCR4 Upregulation in Diffuse Large B-Cell Lymphoma Associated with Prognostic Significance and Clinicopathological Characteristics

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