FADS1 promotes the progression of laryngeal squamous cell carcinoma through activating AKT/mTOR signaling

Zhao, Rui; Tian, Linli; Zhao, Bo; Sun, Yanan; Cao, Jing; Chen, Kexin; Li, Fengqing; Li, Minghua; Shang, Desi; Liu, Ming

doi:10.1038/s41419-020-2457-5

Cited by 39 publications

(30 citation statements)

References 57 publications

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“…Reduced expression of metabolism‐related genes may improve survival of HPV‐positive patients with head and neck cancer (HNC) 16 . FADS1 has emerged as mediator of lipid metabolism gene and drives laryngeal squamous cell carcinoma progression by activating AKT/mTOR signaling pathway 17 . In oral squamous cell carcinoma (OSCC), the Kennedy signaling pathway is upregulated by cholesterol and glycerophospholipid (GPL) metabolic changes 18 .…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of lipid metabolism‐related genes in head and neck squamous cell carcinoma

Xiong

Feng

et al. 2020

Immunity Inflam & Disease

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Background Altered lipid metabolism is involved in the development of many tumors. However, the role of dissimilar lipid metabolism in head and neck squamous cell carcinoma (HNSCC) is not fully established. Aims Here, we sought to determine the prognostic value of lipid metabolism‐related genes in HNSCC. Methods RNA‐seq data and clinical features of 545 HNSCC cases were obtained from The Cancer Genome Atlas database. A regulatory network of transcription factors‐lipid metabolism genes and a risk prognostic model of lipid metabolism‐related genes was developed using bioinformatics and Cox regression modeling. We used tumor immune estimation resource to analyze immune cell infiltration in patients with HNSCC based on the prognostic index (PI) of lipid metabolism‐related genes. Results A total of 136 differentially expressed lipid metabolism genes were identified. Of these, 23 are related to prognosis. In addition to predicting HNSCC prognosis, 11 lipid metabolism‐related genes (ARSI, CYP27B1, CYP2D6, DGKG, DHCR7, LPIN1, PHYH, PIP5K1B, PLA2G2D, RDH16, and TRIB3) also affect HNSCC clinical features (stage, gender, and pathological stage). The PI of lipid metabolism‐related genes embodied the state of HNSCC tumor immune microenvironment.

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Section: Discussionmentioning

confidence: 99%

Prognostic value of lipid metabolism‐related genes in head and neck squamous cell carcinoma

Xiong

Feng

et al. 2020

Immunity Inflam & Disease

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“…In addition, LINC-PINT inhibition increased the phosphorylated levels of the AKT/mTOR pathway-related proteins. The activation of the AKT/mTOR signaling pathway is thought to enhance cancer cell proliferation in LSCC [ 38 ]. Overexpression of EZH2 is able to activate the PI3K/AKT pathway, by which BRCA1 (a tumor suppressor) were exported from nuclei, and aneuploidy and mitotic deficiency were elicited, leading to invasive breast cancer [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

LncRNA LINC-PINT Inhibits Malignant Behaviors of Laryngeal Squamous Cell Carcinoma Cells via Inhibiting ZEB1

Yang¹,

Miao²,

Mao³

et al. 2021

Pathol. Oncol. Res.

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Objective: Laryngeal squamous cell carcinoma (LSCC) belongs to head and neck squamous cell carcinoma (HNSCC), with dismal prognosis. Here, this study aims to disclose the role of LINC-PINT in cancer development, which may contribute to improving the clinical outcomes of LSCC treatment.Methods: LINC-PINT expression in LSCC tissues and in TU-177 and Hep-2 cells was quantified, and subsequently, the association between LINC-PINT and LSCC malignancies was analyzed. pcDNA3.1-LINC-PINT or pcDNA3.1-EZH2 was introduced into Hep-2 and TU-177 cells. qRT-PCR and Western blot analyses examined the levels of proteins related to the AKT/mTOR pathway and their phosphorylated proteins in Hep-2 and TU-177 cells. The viability as well as migration and invasion abilities of Hep-2 and TU-177 cells were determined. Also, the distribution of LINC-PINT in Hep-2 cells was investigated as well as the interplay between LINC-PINT and EZH2. The downstream genes that might interact with EZH2 were screened.Results: LINC-PINT expression was inhibited in LSCC tissues and in Hep-2 and TU-177 cells, whose downregulation was associated with unsatisfactory prognosis. LINC-PINT overexpression suppressed the proliferative, migratory and invasive capacities of Hep-2 and TU-177 cells. LINC-PINT, mainly expressing in nuclei, could enrich EZH2 to silence ZEB1. In Hep-2 and TU-177 cells, the inhibition of LINC-PINT or overexpression of ZEB1 could enhance cell proliferation, migration and invasion. The phosphorylated levels of proteins related to the AKT/mTOR pathway were declined in cells with LINC-PINT overexpression, and the levels of these phosphorylated proteins were increased in cells with LINC-PINT inhibition.Conclusion: LINC-PINT enriches EZH2 to silence ZEB1 and thus inhibits the proliferative, migratory, and invasive capacities of Hep-2 and TU-177 cells. In addition, LINC-PINT might exert its biological function through the AKT/mTOR pathway.

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“…In this context, estradiol down regulated: ZFYVE16, a FYVE zink finger family protein (also called endofin) that regulates cell adhesion and induces cell migration [ 46 ] by regulating TGFβ signaling pathway and is downregulated by ER-β in cancer cells [ 47 ]; and epiregulin, which stimulates cell migration via MAPK activation [ 57 ]. Additionally, estradiol downregulated multiple other genes known to induce cell migration, i.e., B3GNT5, a sphingolipid metabolic enzyme [ 58 ]; FADS1 [ 44 ], MIR1908 (a cholesterol responsive miRNA [ 45 ]); nucleoporin 58 kDa (NUP58) [ 55 ]; TOPORS [ 53 , 54 ]; Six homeobox 4 [ 48 ]; Retinoblastoma binding protein-9 (RBBP9) [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Estradiol Inhibits Human Brain Vascular Pericyte Migration Activity: A Functional and Transcriptomic Analysis

Kurmann

Okoniewski

Dubey

2021

Cells

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Stroke is the third leading cause of mortality in women and it kills twice as many women as breast cancer. A key role in the pathophysiology of stroke plays the disruption of the blood–brain barrier (BBB) within the neurovascular unit. While estrogen induces vascular protective actions, its influence on stroke remains unclear. Moreover, experiments assessing its impact on endothelial cells to induce barrier integrity are non-conclusive. Since pericytes play an active role in regulating BBB integrity and function, we hypothesize that estradiol may influence BBB by regulating their activity. In this study using human brain vascular pericytes (HBVPs) we investigated the impact of estradiol on key pericyte functions known to influence BBB integrity. HBVPs expressed estrogen receptors (ER-α, ER-β and GPER) and treatment with estradiol (10 nM) inhibited basal cell migration but not proliferation. Since pericyte migration is a hallmark for BBB disruption following injury, infection and inflammation, we investigated the effects of estradiol on TNFα-induced PC migration. Importantly, estradiol prevented TNFα-induced pericyte migration and this effect was mimicked by PPT (ER-α agonist) and DPN (ER-β agonist), but not by G1 (GPR30 agonist). The modulatory effects of estradiol were abrogated by MPP and PHTPP, selective ER-α and ER-β antagonists, respectively, confirming the role of ER-α and ER-β in mediating the anti-migratory actions of estrogen. To delineate the intracellular mechanisms mediating the inhibitory actions of estradiol on PC migration, we investigated the role of AKT and MAPK activation. While estradiol consistently reduced the TNFα-induced MAPK and Akt phosphorylation, only the inhibition of MAPK, but not Akt, significantly abrogated the migratory actions of TNFα. In transendothelial electrical resistance measurements, estradiol induced barrier function (TEER) in human brain microvascular endothelial cells co-cultured with pericytes, but not in HBMECs cultured alone. Importantly, transcriptomics analysis of genes modulated by estradiol in pericytes showed downregulation of genes known to increase cell migration and upregulation of genes known to inhibit cell migration. Taken together, our findings provide the first evidence that estradiol modulates pericyte activity and thereby improves endothelial integrity.

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FADS1 promotes the progression of laryngeal squamous cell carcinoma through activating AKT/mTOR signaling

Cited by 39 publications

References 57 publications

Prognostic value of lipid metabolism‐related genes in head and neck squamous cell carcinoma

Prognostic value of lipid metabolism‐related genes in head and neck squamous cell carcinoma

LncRNA LINC-PINT Inhibits Malignant Behaviors of Laryngeal Squamous Cell Carcinoma Cells via Inhibiting ZEB1

Estradiol Inhibits Human Brain Vascular Pericyte Migration Activity: A Functional and Transcriptomic Analysis

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