<i>DIAPH2</i> alterations increase cellular motility and may contribute to the metastatic potential of laryngeal squamous cell carcinoma

Kostrzewska-Poczekaj, Magdalena; Byzia, Ewa; Soloch, Natalia; Jarmuż-Szymczak, Małgorzata; Janiszewska, Joanna; Kowal-Wiśniewska, Ewelina; Paczkowska, Julia; Kiwerska, Katarzyna; Wierzbicka, Małgorzata; Bartochowska, Anna; Ustaszewski, Adam; Greczka, Grażyna; Grénman, Reidar; Szyfter, Krzysztof; Giefing, Maciej

doi:10.1093/carcin/bgz035

Cited by 12 publications

(10 citation statements)

References 28 publications

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“…3 Despite advances in comprehensive LSCC treatment, the 5year survival rate has not decreased significantly in decades. 4 The main risk factors for a poor prognosis of LSCC are invasion and metastasis of cervical lymph nodes. 5 Furthermore, the diagnostic delay caused by the absence of obvious symptoms in the early stage is an unfavorable factor for LSCC prognosis.…”

Section: Introductionmentioning

confidence: 99%

miR-1207-5p suppresses laryngeal squamous cell carcinoma progression by downregulating SKA3 and inhibiting epithelial-mesenchymal transition

Wu¹,

Dai²,

Zhang³

et al. 2021

Molecular Therapy - Oncolytics

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Laryngeal squamous cell carcinoma (LSCC) is the second most common head and neck cancer. Previously, we discovered that miR-1207-5p was downregulated in LSCC. In this study, the clinical significance, function, and mechanism of miR-1207-5p in LSCC were investigated. Downregulation of miR-1207-5p was found to be strongly linked to the malignant progression of LSCC. Functional studies revealed that miR-1207-5p upregulation suppressed LSCC cell proliferation, invasion, migration, and xenograft tumor growth. Bioinformatics analysis revealed that miR-1207-5p target genes were involved in cell cycle regulation, proliferation, adhesion, and the phosphatidylinositol 3kinase (PI3K)/Akt pathway. Mechanistic studies revealed that miR-1207-5p interacts directly with the 3 0 untranslated region of spindle and kinetochore associated complex subunit 3 (SKA3) and downregulates SKA3 expression. Furthermore, SKA3 was found to be overexpressed in LSCC, and its high expression was associated with tumor progression and a poor prognosis. Rescue experiments demonstrated that miR-1207-5p inhibited the malignant phenotypes of LSCC via SKA3. Furthermore, miR-1207-5p upregulation or knockdown of SKA3 inhibited the epithelial-mesenchymal transition (EMT). Collectively, miR-1207-5p inhibited LSCC malignant progression by downregulating SKA3 and preventing EMT. These findings provide new insights into the mechanism of LSCC progression, as well as new potential biomarkers and therapeutic targets for LSCC diagnosis and treatment.

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Section: Introductionmentioning

confidence: 99%

miR-1207-5p suppresses laryngeal squamous cell carcinoma progression by downregulating SKA3 and inhibiting epithelial-mesenchymal transition

Wu¹,

Dai²,

Zhang³

et al. 2021

Molecular Therapy - Oncolytics

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“…DIAPH2 and GASK1B (also known as FAM198B ) have been associated with cancer metastasis ( Kawamata et al 2003 ; Hsu et al 2018 ) . Particularly, DIAPH2 is involved in laryngeal squamous cell carcinoma, a type of cancer with low survival rate ( Kostrzewska-Poczekaj et al 2019 ). Finally, SELENO (also known as SEPS1 ) encodes for a protein that induces inflammatory responses as a result of cellular stress ( Curran et al 2005 ) and diabetes ( Li et al 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes

Tejada‐Martinez

Avelar

Lopes

et al. 2021

Molecular Biology and Evolution

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Within primates, the great apes are outliers both in terms of body size and lifespan, since they include the largest and longest-lived species in the order. Yet, the molecular bases underlying such features are poorly understood. Here, we leveraged an integrated approach to investigate multiple sources of molecular variation across primates, focusing on over ten thousand genes, including ∼1,500 previously associated with lifespan, and additional ∼9,000 for which an association with longevity has never been suggested. We analyzed dN/dS rates, positive selection, gene expression (RNA-seq) and gene regulation (ChIP-seq). By analyzing the correlation between dN/dS, maximum lifespan and body mass we identified 276 genes whose rate of evolution positively correlates with maximum lifespan in primates. Further, we identified 5 genes, important for tumor suppression, adaptive immunity, metastasis and inflammation, under positive selection exclusively in the great ape lineage. RNA-seq data, generated from the liver of six species representing all the primate lineages, revealed that 8% of ∼1,500 genes previously associated with longevity are differentially expressed in apes relative to other primates. Importantly, by integrating RNA-seq with ChIP-seq for H3K27ac (which marks active enhancers), we show that the differentially expressed longevity genes are significantly more likely than expected to be located near a novel “ape-specific” enhancer. Moreover, these particular ape-specific enhancers are enriched for young transposable elements, and specifically SINE-Vntr-Alus (SVAs). In summary, we demonstrate that multiple evolutionary forces have contributed to the evolution of lifespan and body size in primates.

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“…Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck squamous cell carcinomas (HNSCC) [ 1 ]. World has made great strides in LSCC treatment, nonetheless the 5-year survival rate of LSCC patients remains 68% [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Rho-associated kinase1 promotes laryngeal squamous cell carcinoma tumorigenesis and progression via the FAK signaling pathway

et al. 2022

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Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck squamous cell carcinomas (HNSCC). Rho-associated kinase1 (ROCK1) is considered to promote progression of numerous cancers, however, its role in LSCC is still unknown. Here, the expression level of ROCK1 is higher in LSCC tissues than non-tumor tissues, and the expression level of ROCK1 is positively correlated with advanced stage and poor survival prognosis. ROCK1 knockdown in TU686 and TU212 cells dramatically inhibits cellular proliferation, migration and invasion. Whereas the overexpression of ROCK1 reversed these changes. FAK signaling pathway plays an essential role in promoting LSCC progression. Inhibiting FAK activity with TAE226 observably impairs the tumor-promoting effects. In conclusion, ROCK1 promotes LSCC tumorigenesis and progression via the FAK signaling pathway, targeting the ROCK1 molecule may represent potential targets for clinical LSCC treatment.

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DIAPH2 alterations increase cellular motility and may contribute to the metastatic potential of laryngeal squamous cell carcinoma

Cited by 12 publications

References 28 publications

miR-1207-5p suppresses laryngeal squamous cell carcinoma progression by downregulating SKA3 and inhibiting epithelial-mesenchymal transition

miR-1207-5p suppresses laryngeal squamous cell carcinoma progression by downregulating SKA3 and inhibiting epithelial-mesenchymal transition

Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes

Rho-associated kinase1 promotes laryngeal squamous cell carcinoma tumorigenesis and progression via the FAK signaling pathway

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