scholarly journals ERK3 is transcriptionally upregulated by ∆Np63α and mediates the role of ∆Np63α in suppressing cell migration in Non-Melanoma Skin Cancers

2020 ◽  
Author(s):  
Eid S. Alshammari ◽  
Amjad A. Aljagthmi ◽  
Andrew J. Stacy ◽  
Mike Bottomley ◽  
H. Nicholas Shamma ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Luciferase Assay ◽  
Strong Positive Correlation ◽  
Expression Levels ◽  
Positive Correlation ◽  
Melanoma Skin

Abstract Background: p63, a member of the p53 gene family, is an important regulator for epithelial tissue growth and development. ∆Np63α is the main isoform of p63 and highly expressed in Non-melanoma skin cancer (NMSC). Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK) whose biochemical features and cellular regulation are distinct from those of conventional MAPKs such as ERK1/2. While ERK3 has been shown to be upregulated in lung cancers and head and neck cancers, in which it promotes cancer cell migration and invasion, little is known about the implication of ERK3 in NMSCs. Methods: Fluorescent immunohistochemistry was performed to evaluate the expression levels of DNp63a and ERK3 in normal and NMSC specimens. Dunnett’s test was performed to compare mean fluorescence intensity (MFI, indicator of expression levels) of p63 or ERK3 between normal cutaneous samples and NMSC samples (i.e., Actinic Keratosis (AK), a precursor to invasive squamous cell carcinoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC)). A mixed effects (ANOVA) test was used to determine the correlation between DNp63a and ERK3 expression levels (MFI). The regulation of ERK3 by DNp63a was studied by qRT-PCR, Western blot and luciferase assay. The effect of ERK3 regulation by DNp63a on cell migration was measured by performing trans-well migration assay. Results: The expression levels of both ∆Np63α and ERK3 proteins are upregulated in NMSCs compared to normal tissues. There is a strong positive correlation between ∆Np63α and ERK3 expression in normal skin and patients with AK, SCC and BCC. Further, we found that ∆Np63α positively regulates ERK3 transcript and protein levels in A431 and HaCaT skin cells, underlying the upregulation of ERK3 expression and its positive correlation with ∆Np63α in NMSCs. Moreover, similar to the effect of ∆Np63α depletion, silencing ERK3 greatly enhanced A431 cell migration. Restoration of ERK3 expression under the condition of silencing ∆Np63α counteracted the increase in cell migration induced by the depletion of ∆Np63α. Conclusions: ERK3 is positively regulated by ∆Np63α and mediates the role of ∆Np63α in suppressing cell migration in NMSC.

scholarly journals ERK3 is transcriptionally upregulated by ∆Np63α and mediates the role of ∆Np63α in suppressing cell migration in non-melanoma skin cancers

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Eid S. Alshammari ◽  
Amjad A. Aljagthmi ◽  
Andrew J. Stacy ◽  
Mike Bottomley ◽  
H. Nicholas Shamma ◽  
...  
Keyword(s):  
Cell Migration ◽  
Normal Tissue ◽  
Tissue Growth ◽  
Luciferase Assay ◽  
Epithelial Tissue ◽  
Strong Positive Correlation ◽  
Expression Levels ◽  
Positive Correlation ◽  
Melanoma Skin

Abstract Background p63, a member of the p53 gene family, is an important regulator for epithelial tissue growth and development. ∆Np63α is the main isoform of p63 and highly expressed in Non-melanoma skin cancer (NMSC). Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK) whose biochemical features and cellular regulation are distinct from those of conventional MAPKs such as ERK1/2. While ERK3 has been shown to be upregulated in lung cancers and head and neck cancers, in which it promotes cancer cell migration and invasion, little is known about the implication of ERK3 in NMSCs. Methods Fluorescent immunohistochemistry was performed to evaluate the expression levels of ΔNp63α and ERK3 in normal and NMSC specimens. Dunnett’s test was performed to compare mean fluorescence intensity (MFI, indicator of expression levels) of p63 or ERK3 between normal cutaneous samples and NMSC samples. A mixed effects (ANOVA) test was used to determine the correlation between ΔNp63α and ERK3 expression levels (MFI). The regulation of ERK3 by ΔNp63α was studied by qRT-PCR, Western blot and luciferase assay. The effect of ERK3 regulation by ΔNp63α on cell migration was measured by performing trans-well migration assay. Results The expression level of ∆Np63α is upregulated in NMSCs compared to normal tissue. ERK3 level is significantly upregulated in AK and SCC in comparison to normal tissue and there is a strong positive correlation between ∆Np63α and ERK3 expression in normal skin and skin specimens of patients with AK, SCC or BCC. Further, we found that ∆Np63α positively regulates ERK3 transcript and protein levels in A431 and HaCaT skin cells, underlying the upregulation of ERK3 expression and its positive correlation with ∆Np63α in NMSCs. Moreover, similar to the effect of ∆Np63α depletion, silencing ERK3 greatly enhanced A431 cell migration. Restoration of ERK3 expression under the condition of silencing ∆Np63α counteracted the increase in cell migration induced by the depletion of ∆Np63α. Mechanistically, ERK3 inhibits the phosphorylation of Rac1 G-protein and the formation of filopodia of A431 skin SCC cells. Conclusions ERK3 is positively regulated by ∆Np63α and mediates the role of ∆Np63α in suppressing cell migration in NMSC.

scholarly journals ERK3 is transcriptionally upregulated by ∆Np63α and mediates the role of ∆Np63α in suppressing cell migration in Non-Melanoma Skin Cancers

2020 ◽  
Author(s):  
Eid S. Alshammari ◽  
Amjad A. Aljagthmi ◽  
Andrew J. Stacy ◽  
Mike Bottomley ◽  
H. Nicholas Shamma ◽  
...  
Keyword(s):  
Cell Migration ◽  
Normal Tissue ◽  
Tissue Growth ◽  
Luciferase Assay ◽  
Epithelial Tissue ◽  
Strong Positive Correlation ◽  
Expression Levels ◽  
Positive Correlation ◽  
Melanoma Skin

Abstract Background: p63, a member of the p53 gene family, is an important regulator for epithelial tissue growth and development. ∆Np63α is the main isoform of p63 and highly expressed in Non-melanoma skin cancer (NMSC). Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK) whose biochemical features and cellular regulation are distinct from those of conventional MAPKs such as ERK1/2. While ERK3 has been shown to be upregulated in lung cancers and head and neck cancers, in which it promotes cancer cell migration and invasion, little is known about the implication of ERK3 in NMSCs. Methods: Fluorescent immunohistochemistry was performed to evaluate the expression levels of DNp63a and ERK3 in normal and NMSC specimens. Dunnett’s test was performed to compare mean fluorescence intensity (MFI, indicator of expression levels) of p63 or ERK3 between normal cutaneous samples and NMSC samples. A mixed effects (ANOVA) test was used to determine the correlation between DNp63a and ERK3 expression levels (MFI). The regulation of ERK3 by DNp63a was studied by qRT-PCR, Western blot and luciferase assay. The effect of ERK3 regulation by DNp63a on cell migration was measured by performing trans-well migration assay. Results: The expression level of ∆Np63α is upregulated in NMSCs compared to normal tissue. ERK3 level is significantly upregulated in AK and SCC in comparison to normal tissue and there is a strong positive correlation between ∆Np63α and ERK3 expression in normal skin and skin specimens of patients with AK, SCC or BCC. Further, we found that ∆Np63α positively regulates ERK3 transcript and protein levels in A431 and HaCaT skin cells, underlying the upregulation of ERK3 expression and its positive correlation with ∆Np63α in NMSCs. Moreover, similar to the effect of ∆Np63α depletion, silencing ERK3 greatly enhanced A431 cell migration. Restoration of ERK3 expression under the condition of silencing ∆Np63α counteracted the increase in cell migration induced by the depletion of ∆Np63α. Mechanistically, ERK3 inhibits the phosphorylation of Rac1 G-protein and the formation of filopodia of A431 skin SCC cells.Conclusions: ERK3 is positively regulated by ∆Np63α and mediates the role of ∆Np63α in suppressing cell migration in NMSC.

scholarly journals A Case of Squamous Cell Carcinoma of Skin Subsequent to Subcutaneous Foreign Body

2016 ◽  
Vol 12 (1) ◽  
pp. 53-55
Author(s):  
P Anwar ◽  
S Mubashir ◽  
I Hassa ◽  
T Arif
Keyword(s):  
Squamous Cell Carcinoma ◽  
Foreign Body ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Foreign Bodies ◽  
Transposition Flap ◽  
Skin Cancers ◽  
Flap Closure ◽  
Melanoma Skin

Squamous cell carcinoma (SCC) of the skin is one of the most common non melanoma skin cancers (NMSC), along with basal cell carcinoma (BCC). Besides ultraviolet radiation, the role of exposure to industrial agents, ionizing radiation and areas of chronic inflammation is associated with the development of SCC. SCC may also be associated with foreign bodies. We report a rare case of cutaneous SCC in an elderly Kashmiri female, developing subsequent to subcutaneous non metallic foreign body, which was successfully excised with negative margins, and transposition flap closure. DOI: http://dx.doi.org/10.3126/njdvl.v12i1.10604 Nepal Journal of Dermatology, Venereology & Leprology Vol.12(1) 2014 pp.53-55

scholarly journals MicroRNA-625 inhibits cell invasion and epithelial–mesenchymal transition by targeting SOX4 in laryngeal squamous cell carcinoma

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Yuan Li ◽  
Chenjuan Tao ◽  
Lili Dai ◽  
Caixia Cui ◽  
Chaohui Chen ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Expression Levels

AbstractIntroduction: Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer, but the molecular mechanisms underlying its development and progression remain largely elusive. The purpose of the present study is to investigate the expression profile and functional role of microRNA-625 (miR-625) in LSCC.Materials and methods: LSCC tissues and adjacent normal tissues were collected from 86 LSCC patients. The expression levels of miR-625 and SOX4 mRNA in tissues and cells were detected by RT-qPCR analysis. The expression levels of SOX4 and EMT-related proteins were detected by western blot analysis. In vitro cell proliferation, migration, and invasion were detected by MTT assay, colony formation assay, wound healing assay, and transwell invasion assay, respectively. Dual-luciferase reporter assay was performed to verify the binding relationship between miR-625 and the 3′-UTR of SOX4.Results: The results demonstrated that miR-625 is significantly down-regulated in clinical LSCC tissues, and its low expression may be closely associated with unfavorable clinicopathological characteristics of LSCC patients. Overexpression of miR-625 significantly suppressed the proliferation, migration, invasion, and EMT of LSCC cells. Furthermore, SOX4 was validated as a direct target of miR-625 in LSCC cells, and rescue experiments suggested that restoration of SOX4 blocked the tumor suppressive role of miR-625 in LSCC cells.Conclusions: Taken together, these findings highlighted a critical role of miR-625 in the pathogenesis of LSCC, and restoration of miR-625 could be considered as a potential therapeutic strategy against this fatal disease.

scholarly journals Significance of Circular FAT1 as a Prognostic Factor and Tumor Suppressor for Esophageal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Wataru Takaki ◽  
Hirotaka Konishi ◽  
Katsutoshi Shoda ◽  
Tomohiro Arita ◽  
Satoshi Kataoka ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Migration And Invasion ◽  
Cancer Specific Survival ◽  
Tissue Samples ◽  
Expression Levels ◽  
Cell Migration And Invasion

Abstract Background Circular RNA is a novel endogenous non-coding RNA with a stable loop structure, and theories for its biogenesis and usefulness as a biomarker in various cancers have been proposed. The present study investigated the significance of circular FAT1 (circFAT1) as a novel biomarker in esophageal squamous cell carcinoma (ESCC). Method CircFAT1 expression levels were measured in ESCC cell lines and the effects of downregulating circFAT1 on cell migration and invasion were examined using a transwell assay. The functions of miR-548g, which will be sponged by circFAT1, were assessed. Furthermore, the expression of circFAT1 was evaluated in 51 radically resected ESCC tissue samples using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationships between circFAT1 expression, clinicopathological factors, and patient prognosis were analyzed. Results CircFAT1 expression levels were significantly lower in tumor tissue than in adjacent non-tumorous mucosal tissue (p = 0.01). The downregulation of circFAT1 expression promoted ESCC cell migration and invasive ability, but not proliferation. The expression of miR-548g was upregulated by the downregulation of circFAT1. The overexpression of miR-548g also promoted ESCC cell migration and invasion. Recurrence-free survival (p = 0.02) and cancer-specific survival (p = 0.04) rates were significantly higher in patients with elevated circFAT1 expression levels. Conclusion The expression level of circFAT1 is a novel prognostic marker in ESCC patients. New treatment strategies may be developed using the tumor suppressive functions of circFAT1.

scholarly journals Prognosis and functional role of EIF4G1 in lung squamous cell carcinoma

2021 ◽  
Author(s):  
Baoxin Bai ◽  
Lingwei Wang ◽  
Zhiyuan Huang ◽  
Zhiwen Zhang ◽  
Ying Lu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Functional Role ◽  
Lung Squamous Cell Carcinoma ◽  
High Expression ◽  
Expression Levels

Abstract Purpose To study the functional role and prognosis of EIF4G1 in lung squamous cell carcinoma (LSCC). Methods The clinical relevance of EIF4G1 in LSCC was investigated following detection of the expression levels of EIF4G1 by immunohistochemical staining (IHC). The expression levels of EIF4G1, AKT2, p-AKT, mTOR, cyclin D1 and β-actin were detected by western blot analysis. The cell proliferation and colony formation assays were used to detect the cell proliferative ability; flow-cytometry was used to assess the cell cycle; an invasion assay was used to detect cell invasive ability and the real-time quantitative polymerase chain reaction (Q-PCR) assay was used to assess the expression levels of EIF4G1 and β-actin. The role of EIF4G1 was verified by xenograft models. These experimental methods were employed to assess the functional role of EIF4G1 in LSCC pathogenesis. Results EIF4G1 was overexpressed in LSCC tumor tissues (P < 0.05) compared with the corresponding expression noted in paired adjacent tissues and cells. The expression levels of EIF4G1 were dependent on age (P = 0.002) and clinical stage (I vs II vs III + IV) (P < 0.001). High expression of EIF4G1 (P = 0.008, HR = 2.277, 95% CI = 1.250–4.145) could be used to predict the overall survival of LSCC patients as determined by the Cox’s proportional hazard model. High expression of EIF4G1 exhibited a lower survival (LogRank = 7.167, P = 0.007) in LSCC. Downregulation of EIF4G1 significantly inhibited LSCC proliferation, invasion and cell cycle progression. Conclusion EIF4G1 promotes LSCC cell proliferation and may represent an indicator of prognosis in LSCC.

scholarly journals The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4737
Author(s):  
Oliwia Koteluk ◽  
Antonina Bielicka ◽  
Żaneta Lemańska ◽  
Kacper Jóźwiak ◽  
Weronika Klawiter ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Patient Survival ◽  
Gene Set Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Expression Levels

Background: Transmembrane proteins (TMEM) constitute a large family of proteins spanning the entirety of the lipid bilayer. However, there is still a lack of knowledge about their function or mechanism of action. In this study, we analyzed the expression of selected TMEM genes in patients with head and neck squamous cell carcinoma (HNSCC) to learn their role in tumor formation and metastasis. Materials and Methods: Using TCGA data, we analyzed the expression levels of different TMEMs in both normal and tumor samples and compared those two groups depending on clinical-pathological parameters. We selected four TMEMs whose expression was highly correlated with patient survival status and subjected them to further analysis. The pathway analysis using REACTOME and the gene set enrichment analysis (GSEA) were performed to evaluate the association of those TMEMs with genes involved in hallmarks of cancer as well as in oncogenic and immune-related pathways. In addition, the fractions of different immune cell subpopulations depending on TMEM expression were estimated in analyzed patients. The results for selected TMEMs were validated using GEO data. All analyses were performed using the R package, Statistica, and Graphpad Prism. Results: We demonstrated that 73% of the analyzed TMEMs were dysregulated in HNSCC and depended on tumor localization, smoking, alcohol consumption, or HPV infection. The expression levels of ANO1, TMEM156, TMEM173, and TMEM213 correlated with patient survival. The four TMEMs were also upregulated in HPV-positive patients. The elevated expression of those TMEMs correlated with the enrichment of genes involved in cancer-related processes, including immune response. Specifically, overexpression of TMEM156 and TMEM173 was associated with immune cell mobilization and better survival rates, while the elevated ANO1 expression was linked with metastasis formation and worse survival. Conclusions: In this work, we performed a panel of in silico analyses to discover the role of TMEMs in head and neck squamous cell carcinoma. We found that ANO1, TMEM156, TMEM173, and TMEM213 correlated with clinical status and immune responses in HNSCC patients, pointing them as biomarkers for a better prognosis and treatment. This is the first study describing such the role of TMEMs in HNSCC. Future clinical trials should confirm the potential of those genes as targets for personalized therapy of HNSCC.

scholarly journals MiR-101-3p Suppresses Progression of Cervical Squamous Cell Carcinoma by Targeting and Down-Regulating KPNA2

2021 ◽  
Vol 20 ◽  
pp. 153303382110559
Author(s):  
Hong Wang ◽  
Rongxin Xiao ◽  
Biao Yang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Carcinoma Cell ◽  
Cervical Squamous Cell Carcinoma ◽  
Luciferase Assay ◽  
Dual Luciferase Assay ◽  
Functional Assays ◽  
Direct Targeting

Objective We explored mechanism of microRNA-101-3p/Karyopherin α2 (KPNA2) axis in cervical squamous cell carcinoma. Methods: Bioinformatics methods were applied to identify genes for the study. Cell functional assays were implemented to examine the role of the genes in malignant progression of cervical squamous cell carcinoma. Targeting relationship between genes was verified by dual-luciferase assay. Results: MicroRNA-101-3p was lowly expressed in cervical squamous cell carcinoma, while KPNA2 was highly expressed. Dual-luciferase assay identified direct targeting relationship between microRNA-101-3p and KPNA2. Functional assays manifested that highly expressed microRNA-101-3p suppressed cervical squamous cell carcinoma cell growth by targeting KPNA2. Conclusion: Overall, microRNA-101-3p/KPNA2 axis can play an important part in progression of cervical squamous cell carcinoma.

Isoliquiritigenin Inhibits Proliferation and Induces Apoptosis in Tongue Squamous Cell Carcinoma by Modulating miR-21/FOXG1 Pathway

2019 ◽  
Vol 17 (4) ◽  
pp. 463-469
Author(s):  
Hou Deqiang ◽  
Gao Yufeng ◽  
Bai Ning ◽  
Dong Yu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Carcinoma Cells ◽  
Tongue Squamous Cell Carcinoma ◽  
Luciferase Assay ◽  
Forkhead Box ◽  
Proliferation And Apoptosis ◽  
Mrna And Protein Expression ◽  
Induced Apoptosis

Isoliquiritigenin is a flavonoid commonly found in liquorice and has been identified as a potent anti-tumor agent. The aim of this study was to investigate whether isoliquiritigenin regulates the proliferation and apoptosis of tongue squamous cell carcinoma cells by regulating forkhead box G1 expression via miR-21. MTT assay and flow cytometry were used to analyze cell proliferation and apoptosis, respectively. Quantitative real time polymerase chain reaction and western blotting were used to detect mRNA and protein expression levels, respectively. The relationship between miR-21 and forkhead box G1 was detected by dual luciferase assay. Isoliquiritigenin inhibited proliferation and induced apoptosis of tongue squamous cell carcinoma cells, and decreased miR-21 levels and promoted forkhead box G1 expression. Forkhead box G1 was then identified as a target of miR-21 and ISL could promote forkhead box G1 expression by inhibiting miR-21. Further analysis suggested that upregulation of miR-21 improved proliferation and suppressed apoptosis of tongue squamous cell carcinoma cells by inhibiting forkhead box G1 expression. Finally, our results revealed that isoliquiritigenin inhibited proliferation and induced apoptosis of tongue squamous cell carcinoma cells by regulating miR-21. Isoliquiritigenin might act as a novel therapeutic treatment for tongue squamous cell carcinoma cells through up-regulation of forkhead box G1 expression via inhibiting miR-21expression.

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