KRT17 Facilitates Proliferation, Migration and Invasion in Esophageal Squamous Cell Carcinoma by Regulating mTOR/S6K1 pathway

Abstract BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies worldwide which originates from the malignant transformation of esophageal epithelial cells. Dysregulated expression of Keratin17 (KRT17) has been claimed in a variety of malignancies, while its role in ESCC remains unclear. Therefore, our study aimed to explore the potential function and underlying molecular mechanism of KRT17 in ESCC.MethodsData-independent acquisition-mass spectrometry (DIA-MS) workflow was used to analysis KRT17 expression between ESCC and adjacent non-cancerous esophageal tissues. The online database gene expression profiling interactive analysis (GEPIA) was used to further determine the differential expression of KRT17 in tissues. The function of KRT17 in ESCC was tested on two human esophageal cancer cell lines (EC9706 and ECA109). Small interfering RNA (siRNA) was used to inhibit KRT17 expression. Cell proliferation was examined by cell counting kit 8 (CCK8) reagent, colony formation assay, cell cycle distribution analysis and apoptosis. Cell migration was examined by transwell and wound healing assay. Cell invasion was also examined by transwell assay. Western blot and quantitative real-time PCR (qRT-PCR) was used to evaluate protein and mRNA levels, respectively.ResultsKRT17 expression was higher in cancer tissues compared with normal tissues. Transfected with siKRT17 attenuated protein and mRNA levels of KRT17, inhibited proliferation, migration and invasion, and decreased mTOR/S6K1 phosphorylation levels in EC9706 and ECA109.ConclusionKRT17 facilitates proliferation, migration and invasion in ESCC cells, and these cell viability functions were mediated by mTOR/S6K1 pathway.

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Interferon-induced transmembrane protein 1 (IFITM1) is essential for progression of laryngeal squamous cell carcinoma in an Osteopontin/NF-κB-dependent manner

Cancer Biomarkers ◽

10.3233/cbm-201435 ◽

2020 ◽

Vol 29 (4) ◽

pp. 521-529

Author(s):

Yong Yin ◽

Keke Yang ◽

Juanjuan Li ◽

Peng Da ◽

Zhenxin Zhang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Signaling Pathway ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Transmembrane Protein ◽

Migration And Invasion ◽

Dependent Manner ◽

Tissue Samples ◽

Normal Tissues

OBJECTIVE: To assess the expression levels of IFITM1 in human tissue samples and laryngeal squamous cell carcinoma (LSCC) cells, and to explore the potential mechanisms of IFITM1 in LSCC progression. METHODS: Quantitative PCR and immunohistochemical (IHC) assays were performed to detect IFITM1 expression in 62 LSCC tissues and corresponding normal tissues. We further detected the effects of IFITM1 on the proliferation, migration and invasion of LSCC cells and NF-κB signaling pathway through colony formation assay, wound healing assay and transwell assay, respectively. RESULTS: We demonstrated the possible involvement of IFITM1 in the progression of LSCC. We found the upregulated expression of IFITM1 in human LSCC tissues and cells, and analyzed the correlations between IFITM1 expression and osteopontin. Our data further confirmed that IFITM1 affected cell proliferation, migration, and invasion of LSCC cells via the regulation of NF-κB signaling pathway. CONCLUSIONS: We investigated the potential involvement of IFITM1 in the progression of LSCC, and therefore confirmed that IFITM1 was a potential therapeutic target for LSCC.

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NF-κB-Mediated lncRNA AC007271.3 as A ceRNA Promotes Carcinogenesis of Oral Squamous Cell Carcinoma by Regulating Slug

10.21203/rs.3.rs-61547/v1 ◽

2020 ◽

Author(s):

Ze-nan Zheng ◽

Guang-zhao Huang ◽

Qing-qing Wu ◽

Heng-yu Ye ◽

Wei-sen Zeng ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Core Promoter ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Mrna Levels ◽

E Cadherin

Abstract Background: Oral squamous cell carcinoma (OSCC) is the most common oral cancer. Our previous studies confirmed that dysregulation function of long non-coding RNA (lncRNA) AC007271.3 was associated with a poor prognosis and overexpression of AC007271.3 promoted cell proliferation, migration, invasion and inhibited cell apoptosis in vitro, and promoted tumor growth in vivo. However, the underlying mechanisms of AC007271.3 dysregulation remained obscure.Methods: Bioinformatics databases were used to predicted the potential down-stream targeted of AC007271.3 and verified by dual luciferase reporter assay. Core promoter region of AC007271.3 was identified by luciferase activity assay and the potential transcription factor on it was verified by ChIP assay. Western blot and qRT-PCR were performed to detect the protein and messenger RNA (mRNA) levels, respectively. Animal experiments confirmed the metastatic ability in vivo.Results: AC007271.3 functioned as competing endogenous RNA (ceRNA) by binding to miR-125b-2-3p and upregulated the expression of Slug, which is a direct target of miR-125b-2-3p. AC007271.3 enhanced the expression of Slug and inhibited the expression of E-cadherin to promote the migration and invasion in OSCC cells. The expression of AC007271.3 was promoted by canonical nuclear factor-κB (NF-κB) pathway. Conclusion: Our study showed that the classical NF-κB pathway-activated AC007271.3 regulates EMT by miR-125b-2-3p / Slug / E-cadherin axis to promote the development of OSCC, implicating it as a novel potential target for therapeutic intervention in this disease.

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Prognostic role of DFNA5 in head and neck squamous cell carcinoma revealed by systematic expression analysis

BMC Cancer ◽

10.1186/s12885-021-08692-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhiguo Liu ◽

Hongyan Liu ◽

Qian Dong ◽

Hongyu Li ◽

Bin Zhang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Prognostic Value ◽

Prognostic Significance ◽

Neck Squamous Cell Carcinoma ◽

Mrna Levels ◽

Strong Positive Correlation ◽

Normal Tissues

Abstract Background The gasdermin E gene (GSDME, also known as DFNA5) is mutated in familial aging-related hearing loss. Recent studies have also revealed that the expression of DFNA5 is suppressed in many cancer types; however, little is known about the function of DFNA5 in head and neck squamous cell carcinoma (HNSCC). Accordingly, the aim of the present study was to evaluate the expression of DFNA5 and explore its prognostic value in HNSCC. Result We used a set of bioinformatics tools, including Oncomine, TIMER, TISIDB, cBioPortal, and GEPIA, to analyze the expression of DFNA5 in patients with HNSCC from public databases. Kaplan-Meier plotter was used to evaluate the potential prognostic significance of DFNA5. DFNA5 mRNA levels were significantly higher in HNSCC tissues than in normal tissues, and high DFNA5 expression was correlated with worse survival. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that DFNA5 expression has a strong positive correlation with cell adhesion and the integrin signaling pathway, whereas its expression was negatively correlated with the levels of infiltrating B cells (cor = − 0.223, P = 8.57e-07) and CD8 T cells (cor = − 0.223, P = 2.99e-07). Conclusion This study demonstrates that DFNA5 expression has prognostic value for HNSCC patients. Moreover, these results suggest that regulation of lymphocyte infiltration is the mechanism underlying the function of DFNA5 in HNSCC.

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LncRNA MCM3AP-AS1 promotes proliferation, migration and invasion of oral squamous cell carcinoma cells via regulating miR-204-5p/FOXC1

Journal of Investigative Medicine ◽

10.1136/jim-2020-001415 ◽

2020 ◽

Vol 68 (7) ◽

pp. 1282-1288

Author(s):

Hui Li ◽

Junhong Jiang

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Molecular Mechanisms ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Qrt Pcr ◽

Gene Assay

Oral squamous cell carcinoma (OSCC) is a lethal malignancy. It is reportedly demonstrated that long non-coding RNA (lncRNA) participates in the development of OSCC. The purpose of this study was to clarify the function and possible molecular mechanisms of lncRNA MCM3AP antisense RNA 1 (lncRNA MCM3AP-AS1) in OSCC. Quantitative real-time PCR (qRT-PCR) was adopted to investigate MCM3AP-AS1 expressions in OSCC tissues and cells. The proliferation, migration and invasion of HN-6 and SCC-9 cells were probed by cell counting kit-8 and Transwell assays, respectively. Dual luciferase reporter gene assay, Pearson’s correlation analysis, qRT-PCR and western blot were used to detect the binding relationship among miR-204-5 p, MCM3AP-AS1 and forkheadbox C1 (FOXC1). MCM3AP-AS1 expression was elevated in OSCC tissues and cell lines. Overexpression of MCM3AP-AS1 facilitated the proliferation, migration and invasion of OSCC cells, while the knockdown of MCM3AP-AS1 suppressed these malignant phenotypes. Besides, MCM3AP-AS1 impeded miR-204-5 p by binding with it. MCM3AP-AS1 could also upregulate the expression of FOXC1 via repressing miR-204-5 p.MCM3AP-AS1 promotes the progression of OSCC cells by adsorbing miR-204-5 p and upregulating FOXC1 expressions.

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Circular RNA circ_0006168 enhances Taxol resistance in esophageal squamous cell carcinoma by regulating miR-194-5p/JMJD1C axis

Cancer Cell International ◽

10.1186/s12935-021-01984-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fanyong Qu ◽

Lina Wang ◽

Caiyan Wang ◽

Lingxia Yu ◽

Kaikai Zhao ◽

...

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Taxol Resistance

Abstract Background Chemoresistance is one of the major obstacles for cancer therapy in the clinic. Circular RNAs (circRNAs) are involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and chemoresistance. This study aimed to explore the role and molecular mechanism of circ_0006168 in Taxol resistance of ESCC. Methods The expression levels of circ_0006168, microRNA-194-5p (miR-194-5p) and jumonji domain containing 1C (JMJD1C) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The half-inhibition concentration (IC50) value of Taxol was evaluated by Cell Counting Kit-8 (CCK-8) assay. Cell proliferation was evaluated by CCK-8 and colony formation assays. Cell migration and invasion were detected by transwell assay. Cell apoptosis was determined by flow cytometry. The interaction between miR-194-5p and circ_0006168 or JMJD1C was predicted by bioinformatics analysis (Circinteractome and TargetScan) and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) and RNA pull-down assays. The mice xenograft model was established to investigate the roles of circ_0006168 in vivo. Results Circ_0006168 and JMJD1C were upregulated and miR-194-5p was downregulated in ESCC tissues, ESCC cells, and Taxol-resistant cells. Functionally, knockdown of circ_0006168 or JMJD1C increased Taxol sensitivity of ESCC in vitro via inhibiting cell proliferation, migration and invasion, and promoting apoptosis. Moreover, circ_0006168 could directly bind to miR-194-5p and JMJD1C was verified as a direct target of miR-194-5p. Mechanically, circ_0006168 was a sponge of miR-194-5p to regulate JMJD1C expression in ESCC cells. Furthermore, JMJD1C overexpression reversed the promotive effect of circ_0006168 knockdown on Taxol sensitivity. Besides, circ_0006168 silence suppressed tumor growth in vivo. Conclusion Circ_0006168 facilitated Taxol resistance in ESCC by regulating miR-194-5p/JMJD1C axis, providing a promising therapeutic target for ESCC chemotherapy.

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BAG2 overexpression correlates with growth and poor prognosis of esophageal squamous cell carcinoma

Open Life Sciences ◽

10.1515/biol-2018-0069 ◽

2018 ◽

Vol 13 (1) ◽

pp. 582-588

Author(s):

Ying-Cai Hong ◽

Zheng Wang ◽

Bin Peng ◽

Li-Gang Xia ◽

Lie-Wen Lin ◽

...

Keyword(s):

Gene Expression ◽

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

The Cancer Genome Atlas ◽

Cell Counting ◽

Migration And Invasion ◽

Small Interference Rna

AbstractPrevious studies have suggested that Bcl2-associated athanogene 2 (BAG2) serves as a crucial regulator for tumorigenesis in multiple tumors. However, little is known about the effect of BAG2 on esophageal squamous cell carcinoma (ESCC). This study focused on investigating whether BAG2 functions as a cancer-promoting gene in ESCC. In this work, gene expression data and clinical information from the NCBI Gene Expression Omnibus (GEO), Oncomine and The Cancer Genome Atlas (TCGA) were collected and analyzed. Expression of BAG2 in ESCC was determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). BAG2 was knocked down using small interference RNA (si-RNA) approach. Cell proliferation, migration and invasion were assessed by Cell Counting Kit-8 (CCK-8) and transwell assays. Molecular mechanism was detected by western blotting assay. The expression of BAG2 both in ESCC tissues and cells was upregulated and overexpression was associated with worsened prognosis. BAG2 silencing inhibited ESCC cell proliferation, migration and invasion, which was regulated by the phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway. These results reveal contributions of BAG2 as a predictor and potential therapeutic target in ESCC.

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Long Non-Coding RNA LINC01929 Accelerates Progression of Oral Squamous Cell Carcinoma by Targeting the miR-137-3p/FOXC1 Axis

Frontiers in Oncology ◽

10.3389/fonc.2021.657876 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hongze Che ◽

Yanhai Che ◽

Zhimin Zhang ◽

Qing Lu

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Cell Lines ◽

Squamous Cell ◽

Cell Counting ◽

Migration And Invasion ◽

Tissue Samples ◽

Non Coding Rna ◽

Luciferase Activity Assay

Recently, additional long noncoding RNAs (lncRNAs) have been identified and their possible roles were investigated in a variety of human tumors. One of these lncRNAs, LINC01929, promoted the progression of some cancers, whereas its expression and biological function in human oral squamous cell carcinoma (OSCC) remains still mostly uncertain. The LINC01929 expression in OSCC tissues or cell lines was identified via quantitative real-time polymerase chain reaction. The cell counting kit-8, transwell migration, wound-healing, and flow cytometry assays were utilized to characterize the functions of LINC01929 in OSCC cells. The interactive relationships between LINC01929 and miR-137-3p, miR-137-3p and Forkhead box C1 (FOXC1) were investigated by the dual-luciferase activity assay. Our findings demonstrated that LINC01929 was highly expressed in OSCC tissue samples and cell lines, whereas miR-137-3p expression was downregulated. LINC01929 acted as a carcinogenic lncRNA with accelerated OSCC cell proliferation, migration and invasion, and suppression of apoptosis. We further indicated that LINC01929 facilitated tumor growth in xenograft mouse models. Mechanistically, LINC01929 acted as a sponge for miR-137-3p to elevate FOXC1 expression, which is the target of miR-137-3p. In addition, downregulated miR-137-3p expression rescued the suppressive behaviors of LINC01929 knockdown on the biological behaviors of OSCC cells. Taken together, LINC01929 functioned as a tumor-promoting lncRNA via the miR-137-3p/FOXC1 axis in OSCC, suggesting novel targets for OSCC therapy.

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MicroRNA-573 inhibits cell proliferation, migration and invasion and is downregulated by PICSAR in cutaneous squamous cell carcinoma

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2021.6301 ◽

2021 ◽

Author(s):

Yanhua Wang ◽

Shengjian Tang ◽

Jianping Lv

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cutaneous Squamous Cell Carcinoma ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Tumor Tissues ◽

Regulatory Effects

The incidence of cutaneous squamous cell carcinoma (cSCC) has been increasing in recent years. Meanwhile, microRNAs (miRNAs) have been found to play vital roles in various cancers, including cSCC. This study aimed to investigate the expression of microRNA-573 (miR-573) in cSCC, its relationship with long non-coding RNA PICSAR and analyze its biological role. The relationship between PICSAR and miR-573 was confirmed by dual-luciferase reporter assay and Pearson’s correlation coefficient analysis. The levels of PICSAR and miR-573 were measured using quantitative Real-Time PCR. Cell Counting Kit-8 assay was used to evaluate the cSCC cell proliferation ability. The migration and invasion abilities of cSCC cells were evaluated by Transwell assay. PICSAR expression was increased and miR-573 was decreased in tumor tissues and cSCC cell lines. PICSAR and miR-573 can bind directly, and miR-573 expression was downregulated by PICSAR in cSCC. Overexpression of miR-573 significantly inhibited the proliferation, migration and invasion abilities of A431 and SCC13 cells. Additionally, miR-573 overexpression reversed the promotion effects of PICSAR overexpression on cSCC cell proliferation, migration and invasion abilities. In conclusion, our findings indicated that miR-573 expression was decreased in tumor tissues and cSCC cells and was downregulated by PICSAR in cSCC. Additionally, miR-573 overexpression inhibited cSCC cell proliferation, migration and invasion, and reversed the promotion effects of PICSAR overexpression on cSCC cell biological functions. Thus, miR-573 might function as a tumor suppressor and might be involved in the regulatory effects of PICSAR on tumorigenesis in cSCC.

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ETV5 overexpression promotes progression of esophageal squamous carcinoma by upregulating SKA1 and TRPV2

10.21203/rs.3.rs-820720/v1 ◽

2021 ◽

Author(s):

Mingchuang Sun ◽

Kang Fang ◽

Zhaoxing Li ◽

Yuan Chu ◽

Aiping Xu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Tumor Metastasis ◽

Cell Counting ◽

Luciferase Reporter ◽

Clinicopathological Parameters ◽

Migration And Invasion ◽

Rapid Progression

Abstract Background Esophageal squamous cell carcinoma (ESCC) is notorious for the rapid progression especially early tumor metastasis due to the unclear mechanism. Recently, ETV5 attracts much attention for its potential role as an oncogenic transcription factor involved in multiple cancers. However, no one reported the mechanism behind the association between ETV5 expression and Esophageal squamous cell carcinoma (ESCC) progression. Therefore, in this study, we aimed to investigate the role of ETV5 in ESCC. Methods The Cancer Genome Atlas (TCGA) and GEO database was used to explore ETV5 expression in ESCC. ECA109, KYSE150 and TE1 cell lines were used in the experiments. The Cell Counting Kit 8 (CCK8), migration, invasion, wound healing assays were exerted to evaluate proliferation, migration and invasion of ESCC cells. RNA sequencing was performed to find downstream genes regulated by ETV5. Real-time PCR, Western blotting, Chromatin immunoprecipitation (CHIP) and Dual luciferase reporter assays were used to assess the underlying mechanism. Immunohistochemistry was used to evaluate the relationship between ETV5 expression, clinicopathological parameters and patient prognosis. Tumor metastasis was investigated in BALB/c nude mice. Results ETV5 was observed upregulated in ESCC both from online database and our ESCC tissues and ETV5 was associated with tumor staging. Knockdown of ETV5 or its downstream genes SKA1 and TRPV2 significantly suppress ESCC cells migration and invasion, respectively. Additionally, in vivo study showed knockdown of ETV5 inhibited tumor metastasis. Further experiments unveiled ETV5 could transcriptionally upregulate the expression of SKA1 and TRPV2 and further activate MMPs in ESCC progression. Conclusion ETV5 promoted metastasis of ESCC by activating MMPs through augmenting the transcription of SKA1 and TRPV2. ETV5 was likely to be a novel diagnostic marker and therapeutic target in ESCC treatment.

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Prognostic Role of DFNA5 in Head and Neck Squamous Cell Carcinoma Revealed by Systematic Expression Analysis

10.21203/rs.3.rs-114898/v1 ◽

2020 ◽

Author(s):

Zhiguo Liu ◽

Hongyan Liu ◽

Qian Dong ◽

Hongyu Li ◽

Bin Zhang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Prognostic Value ◽

Prognostic Significance ◽

Neck Squamous Cell Carcinoma ◽

Mrna Levels ◽

Strong Positive Correlation ◽

Normal Tissues

Abstract The gasdermin E gene (GSDME, also known as DFNA5) is mutated in familial aging-related hearing loss. Recent studies have also revealed that the expression of DFNA5 is suppressed in many cancer types; however, little is known about the function of DFNA5 in head and neck squamous cell carcinoma (HNSCC). Accordingly, the aim of the present study was to evaluate the expression of DFNA5 and explore its prognostic value in HNSCC. We used a set of bioinformatics tools, including Oncomine, TIMER, TISIDB, cBioPortal, and GEPIA, to analyze the expression of DFNA5 in patients with HNSCC from public databases. Kaplan-Meier plotter was used to evaluate the potential prognostic significance of DFNA5. DFNA5 mRNA levels were significantly higher in HNSCC tissues than in normal tissues, and high DFNA5 expression was correlated with worse survival. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that DFNA5 expression has a strong positive correlation with cell adhesion and the integrin signaling pathway, whereas its expression was negatively correlated with the levels of infiltrating B cells (cor = –0.223, P = 8.57e-07) and CD8 T cells (cor = –0.223, P = 2.99e-07). Overall, this study demonstrates that DFNA5 expression has prognostic value for HNSCC patients. Moreover, these results suggest that regulation of lymphocyte infiltration is the mechanism underlying the function of DFNA5 in HNSCC.

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