FAM134B promotes esophageal squamous cell carcinoma in vitro and its correlations with clinicopathologic features

Islam, Farhadul; Gopalan, Vinod; Law, Simon; Tang, Johnny; Lam, Alfred King-Yin

doi:10.1016/j.humpath.2018.11.033

Cited by 21 publications

(11 citation statements)

References 30 publications

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“…In addition, higher expressions of EPAS1 protein in mutated samples indicate tumour-supporting roles of EPAS1 in the pathogenesis of phaeochromocytoma/paraganglioma. Previous studies reported that dysregulation and gain-of-function mutation of EPAS1 associated with neuroendocrine tumours such as paraganglioma and phaeochromocytomas by inducing pseudo-hypoxic tumour microenvironment [9,13,39]. Thus, the findings of the current study agree with previous studies.…”

Section: Discussionsupporting

confidence: 92%

“…Recent studies have demonstrated that mutations in endothelial PAS domain-containing protein 1 (EPAS1) is associated with manifestations of phaeochromocytomas and paragangliomas [1,9,[12][13][14]. EPAS1, also known as HIF-2α, encodes for one of the hypoxia inducible factor (HIF) family members, which is involved in the hypoxic response [15].…”

Section: Introductionmentioning

confidence: 99%

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Identification of Novel Mutations and Expressions of EPAS1 in Phaeochromocytomas and Paragangliomas

Islam

Pillai

Gopalan

et al. 2020

Genes

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Endothelial PAS domain-containing protein 1 (EPAS1) is an oxygen-sensitive component of the hypoxia-inducible factors (HIFs) having reported implications in many cancers by inducing a pseudo-hypoxic microenvironment. However, the molecular dysregulation and clinical significance of EPAS1 has never been investigated in depth in phaeochromocytomas/paragangliomas. This study aims to identify EPAS1 mutations and alterations in DNA copy number, mRNA and protein expression in patients with phaeochromocytomas/paragangliomas. The association of molecular dysregulations of EPAS1 with clinicopathological factors in phaeochromocytomas and paragangliomas were also analysed. High-resolution melt-curve analysis followed by Sanger sequencing was used to detect mutations in EPAS1. EPAS1 DNA number changes and mRNA expressions were examined by polymerase chain reaction (PCR). Immunofluorescence assay was used to study EPAS1 protein expression. In phaeochromocytomas, 12% (n = 7/57) of patients had mutations in the EPAS1 sequence, which includes two novel mutations (c.1091A > T; p.Lys364Met and c.1129A > T; p.Ser377Cys). Contrastingly, in paragangliomas, 7% (n = 1/14) of patients had EPAS1 mutations and only the c.1091A > T; p.Lys364Met mutation was detected. In silico analysis revealed that the p.Lys364Met mutation has pathological potential based on the functionality of the protein, whereas the p.Ser377Cys mutation was predicted to be neutral or tolerated. The majority of the patients had EPAS1 DNA amplification (79%; n = 56/71) and 53% (n = 24/45) patients shown mRNA overexpression. Most of the patients with EPAS1 mutations exhibited aberrant DNA changes, mRNA and protein overexpression. In addition, these alterations of EPAS1 were associated with tumour weight and location. Thus, the molecular dysregulation of EPAS1 could play crucial roles in the pathogenesis of phaeochromocytomas and paragangliomas.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Identification of Novel Mutations and Expressions of EPAS1 in Phaeochromocytomas and Paragangliomas

Islam

Pillai

Gopalan

et al. 2020

Genes

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“…The expression of caspases -3, -8, -9 in SW480 and SW48 followed by treated with KRL in cells pretreated with respective inhibitors in and SW480 cell lines were significantly inhibited by KRL. The inhibitory effects were higher than that of the pea lectin [16].…”

Section: Krl Induced Activation Mitochondrial Intrinsic Apoptotic Patmentioning

confidence: 65%

Kaempferia rotunda tuberous rhizome lectin induces apoptosis and growth inhibition of colon cancer cells in vitro

Islam

Gopalan

Lam

et al. 2019

International Journal of Biological Macromolecules

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Five ESCC cancer cell lines (KYSE70, KYSE150, KYSE450, KYSE520, and HKESC-1) and one nonneoplastic keratinocyte (HaCaT) were used in the present study. All the cells were maintained as previously described (26,27).…”

Section: Cell Culturementioning

confidence: 99%

“…Subsequently, the clones were stained with crystal violet (0.5%) for 2 h at room temperature and washed with tap water. Finally, after being air-dried, images of the plates were taken, and clone formation rates were calculated as previously described (26).…”

Section: Colony Formation Assaymentioning

confidence: 99%

Molecular Deregulation of EPAS1 in the Pathogenesis of Esophageal Squamous Cell Carcinoma

et al. 2020

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Endothelial PAS domain-containing protein 1 (EPAS1) is an angiogenic factor and its implications have been reported in many cancers but not in esophageal squamous cell carcinoma (ESCC). Herein, we aim to examine the genetic and molecular alterations, clinical implications, and functional roles of EPAS1 in ESCC. High-resolution melt-curve analysis and Sanger sequencing were used to detect mutations in EPAS1 sequence. EPAS1 DNA number changes and mRNA expressions were analyzed by polymerase chain reaction. in vitro functional assays were used to study the impact of EPAS1 on cellular behaviors. Overall, 7.5% (n = 6/80) of patients with ESCC had mutations in EPAS1, and eight novel variants (c.1084C>T, c.1099C>A, c.1145_1145delT, c.1093C>G, c.1121T>G, c.1137_1137delG, c.1135_1136insT, and c.1091_1092insT) were detected. Among these mutations, four were frameshift (V382Gfs * 12, A381Lfs * 13, K379Ifs * 6, and K364Nfs * 12) mutations and showed the potential of nonsense mediated mRNA decay (NMD) in computational analysis. The majority of patients showed molecular deregulation of EPAS1 [45% (n = 36/80) DNA amplification, 42.5% (n = 34/80) DNA deletion, as well as 53.7% (n = 43/80) high mRNA expression, 20% (n = 16/80) low mRNA expression]. These alterations of EPAS1 were associated with tumor location and T stages. Patients with stage III ESCC having EPAS1 DNA amplification had poorer survival rates in comparison to EPAS1 DNA deletion (p = 0.04). In addition, suppression of EPAS1 in ESCC cells showed reduced proliferation, wound healing, migration, and invasion in comparison to that of control cells. Thus, the molecular and functional studies implied that EPAS1 plays crucial roles in the pathogenesis of ESCC and has the potential to be used as a prognostic marker and as a therapeutic target.

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FAM134B promotes esophageal squamous cell carcinoma in vitro and its correlations with clinicopathologic features

Cited by 21 publications

References 30 publications

Identification of Novel Mutations and Expressions of EPAS1 in Phaeochromocytomas and Paragangliomas

Identification of Novel Mutations and Expressions of EPAS1 in Phaeochromocytomas and Paragangliomas

Kaempferia rotunda tuberous rhizome lectin induces apoptosis and growth inhibition of colon cancer cells in vitro

Molecular Deregulation of EPAS1 in the Pathogenesis of Esophageal Squamous Cell Carcinoma

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