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

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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RNA-Seq revealing the tumor immunity regulation mechanism of circular RNA in human laryngeal squamous cell carcinomas

10.21203/rs.3.rs-29486/v1 ◽

2020 ◽

Author(s):

Tianyu Cui ◽

Menghua Li ◽

Cheng Lu ◽

Min Xia ◽

Zhaoyang Ke ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Signaling Pathway ◽

Tumor Immunity ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Circular Rna ◽

Tissue Samples ◽

Screening Criteria ◽

Kegg Analysis

Abstract Background Motivation: Laryngeal squamous cell carcinoma (LSCC) is one of the relatively common malignant tumors occurring in the epithelial tissue of the larynx. Recently study showed that tumor immunity mechanisms have highly correlation with the development and progression of LSCC. With the development of research on circular RNA (circRNA) in recent years, a large number of abnormal expressions of circRNA in various tumors have been reported. There is a large number of evidences indicated that circRNA is widely involved in stage development of tumors and it also plays an important role as a biomarker in diagnosis and treatment. Therefore, the study of the pathways involved in the development of tumor by circRNA is a necessary process for humans to further understand cancer at the transcriptional level. The purpose of this study was to identify the circRNAs in tumor tissues of patients with laryngeal squamous cell carcinoma (LSCC) by NGS technique and to find the circRNAs that were significantly different from normal adjacent tissues. Finally, the mechanism of these differentially expressed tumor immunity circRNAs affecting LSCC development was further analyzed. Methods Raw data was mapped to Hg19 human genome and circRNA read count matrix was generated by featureCount software. In this study, the screening criteria for differential expression were p-value < 0.01 and | log2(FoldChange) | > 2.0. Filtered circRNAs were then applied for generating circRNA-miRNA-mRNA interaction network with known human micro RNA (miRNAs). After filtering unmeaning interactions, network-involved mRNAs were implement to KEGG analysis. Among those KEGG terms, immunity-related pathways were selected and their related circRNAs were chosen for further analysis. Second KEGG analysis then performed to these circRNAs for detecting their potential to be biomarkers. Finally a QRT-PCR experiment was used to verify the results. Results Among the 8 samples, 4 were LSCC tumor tissue samples and 4 were adjacent normal tissue samples. A total of 75,931 circRNAs were identified in total 8 samples. After filtering through the above screening criteria, we obtained 39 significantly differential expressed circRNAs from those identified candidates. Of the 39 circRNAs, 21 were detected to be significantly less expressed in LSCC tissues than in adjacent normal tissues, and other 18 were significantly higher. Through the interaction analysis of circRNA-miRNA-mRNA, we found that these differential expressed circRNAs were related to tumor immunity. After screening, four circRNAs with the strongest correlation with tumor immunity were obtained. We found that they play an important role in the membrane receptor tyrosine protein kinase signaling pathway pathway (Ras-Raf-MAPK pathway) and p53 signaling pathway. Conclusion According to the results, the method of detecting expression of four selected circRNAs has a bright future to be a kind of new LSCC diagnose approach.

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LncRNA TM4SF19-AS1 Promotes the Proliferation, Migration and Invasion of Laryngeal Squamous Cell Carcinoma by Targeting miR-153-3p/ITGAV Axis

10.21203/rs.3.rs-720370/v1 ◽

2021 ◽

Author(s):

Yudong Liu ◽

Xiaojuan Feng ◽

Yuexin Tian ◽

Yanzhuo Zhang ◽

Huan Cao ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Subcellular Location ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Tissue Samples ◽

Node Metastasis ◽

Dual Luciferase Reporter Assay

Abstract Background: LncRNA plays an important role in the gene regulatory network and can affect the progress of tumors. LncRNA TM4SF19-AS1 has been reported may associate with the occurrence and development of head and neck squamous cell carcinoma. Methods: LncRNA TM4SF19-AS1 expression in laryngeal squamous cell carcinoma (LSCC) tissue samples was evaluated in TCGA database, and its expression in LSCC tissues and cells was further determined via qRT-PCR. CCK-8, EdU, wound healing and transwell assays were performed to access the cell biological behaviors of TM4SF19-AS1. The downstream regulatory mechanism of TM4SF19-AS1 regulating gene expression was further detected by WGCNA, subcellular location prediction, western blot and dual-luciferase reporter assay.Results: The expression of TM4SF19-AS1 was upregulated in LSCC tissues and positively correlated with tumor-node-metastasis (TNM) stage and lymph node metastasis in LSCC patients. Knockdown of TM4SF19-AS1 suppressed the proliferation, migration and invasion of LSCC cells. Mechanistically, TM4SF19-AS1 acted as a competing endogenous RNA (ceRNA) that directly bound to miR-153-3p, and ITGAV was the direct target of miR-153-3p.Conclusions: LncRNA TM4SF19-AS1 promotes the proliferation, migration and invasion of laryngeal carcinoma by targeting miR-153-3p/ITGAV axis, suggesting that TM4SF19-AS1 could be a potential diagnostic biomarker and an effective target for the treatment for LSCC.

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Effects of Polygonatum sibiricum Polysaccharides (PSP) on Human Esophageal Squamous Cell Carcinoma (ESCC) via NF-κB Signaling Pathway

International Journal of Polymer Science ◽

10.1155/2019/3852879 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

Weizheng Zhou ◽

Jiang Hong ◽

Ji Zhu ◽

Xiaowei Wang

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Signaling Pathway ◽

Squamous Cell ◽

Migration And Invasion ◽

Control Group ◽

Dependent Manner ◽

Rt Pcr ◽

Expression Levels

Objective. To explore the effects of different concentrations of Polygonatum sibiricum polysaccharides (PSP) on human esophageal squamous cell carcinoma (ESCC) cell line Eca109 and explore the new approach for the treatment of ESCC. Methods. Eca109 cells were divided into 5 groups, including one control group and 4 experimental groups where the concentrations of PSP used were 50, 100, 200, and 400 μg/mL. The proliferation rate of Eca109 cells in each group was measured with the CCK8 assay, and the apoptosis rate in each group was analyzed by flow cytometry; the in vitro scratch assay was used to determine the migration ability of Eca109 cells after PSP treatment; the expression levels of IL-1, IL-6, IL-10, TNF-α, and TGF-β were measured by RT-PCR, and the expression levels of TLR4 and proteins that are related to NF-κB signaling pathways were determined by Western blot. Results. PSP significantly inhibited the proliferation of Eca109 cells (p<0.05) on a time- and dose-dependent manner; the apoptosis rates of Eca109 cells in experimental groups were significantly increased after 48 h of culture (p<0.05); PSP significantly reduced the migration and invasion ability of Eca109 cells (p<0.05); RT-PCR results showed that the expression of IL-10 in Eca109 cells increased significantly after treatment with PSP (p<0.05), while the expression of IL-1, IL-6, TNF-α, and TGF-β decreased significantly (p<0.05). Compared with the control group, the expression level of TLR4, NF-κB/p50, and NF-κB/p65 protein in each experimental group was significantly lower than that in the control group (p<0.05). Conclusions. PSP significantly inhibited the proliferation, invasion, and migration of Eca109 cells and promoted cell apoptosis. These observed effects were probably due to the PSP’s inhibition on the NF-κB signaling pathway in Eca109 cells via the regulation of the TLR4 expression.

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OTX1 exerts an oncogenic role and is negatively regulated by miR129-5p in laryngeal squamous cell carcinoma

10.21203/rs.3.rs-21929/v3 ◽

2020 ◽

Author(s):

Xiu-Ping Tu ◽

Hao Li ◽

Liang-Si Chen ◽

Xiao-Ning Luo ◽

Zhong-Ming Lu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Tumor Growth ◽

Cell Carcinoma ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Migration And Invasion ◽

Tissue Samples ◽

Direct Target

Abstract Background Orthodenticle homeobox 1 (OTX1) is a transcription factor that plays an important role in various human cancers. However, the function of OTX1 in laryngeal squamous cell carcinoma (LSCC) is largely unknown. We aimed to explore the roles of OTX1 in LSCC and its possible molecular mechanism.Methods The expression levels of OTX1 were assessed in LSCC cell lines and tissue samples. We further examined the effect of OTX1 on LSCC progression. The upstream regulator of OTX1 was identified using a computer algorithm and confirmed experimentally. Results OTX1 was highly expressed in 70.7% (70/99) of LSCC tissue samples. The OTX1 expression in LSCC was significantly correlated with lymph node metastasis. High OTX1 expression in patients with LSCC was correlated with poor prognosis. Knockdown of OTX1 inhibited proliferation, colony formation, migration and invasion in LSCC cells. Knockdown of OTX1 inhibited tumor growth in a xenograft mouse model. Mechanistically, OTX1 might act as a direct target of miR-129-5p. OTX1 enhanced tumorigenicity and tumor growth both in vitro and in vivo. Conclusions Our findings support that OTX1 is an oncogene in LSCC tumorigenesis and progression. Furthermore, OTX1 is a direct target of miR-129-5p in LSCC cells. Taken together, OTX1 is a promising diagnostic and therapeutic marker for LSCC.

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OTX1 exerts an oncogenic role and is negatively regulated by miR129-5p in laryngeal squamous cell carcinoma

10.21203/rs.3.rs-21929/v2 ◽

2020 ◽

Author(s):

Xiu-Ping Tu ◽

Hao Li ◽

Liang-Si Chen ◽

Xiao-Ning Luo ◽

Zhong-Ming Lu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Tumor Growth ◽

Cell Carcinoma ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Migration And Invasion ◽

Tissue Samples ◽

Direct Target

Abstract Background Orthodenticle homeobox 1 (OTX1) is a transcription factor that plays an important role in various human cancers. However, the function of OTX1 in laryngeal squamous cell carcinoma (LSCC) is largely unknown. We aimed to explore the roles of OTX1 in LSCC and its possible molecular mechanism. Methods The expression levels of OTX1 were assessed in LSCC cell lines and tissue samples. We further examined the effect of OTX1 on LSCC progression. The upstream regulator of OTX1 was identified using a computer algorithm and confirmed experimentally. Results OTX1 was highly expressed in 70.7% (70/99) of LSCC tissue samples. The OTX1 expression in LSCC was significantly correlated with lymph node metastasis. High OTX1 expression in patients with LSCC was correlated with poor prognosis. Knockdown of OTX1 inhibited proliferation, colony formation, migration and invasion in LSCC cells. Knockdown of OTX1 inhibited tumor growth in a xenograft mouse model. Mechanistically, OTX1 might act as a direct target of miR-129-5p. OTX1 enhanced tumorigenicity and tumor growth both in vitro and in vivo . Conclusions Our findings support that OTX1 is an oncogene in LSCC tumorigenesis and progression. Furthermore, OTX1 is a direct target of miR-129-5p in LSCC cells. Taken together, OTX1 is a promising diagnostic and therapeutic marker for LSCC.

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OTX1 Exerts an Oncogenic Role and is Negatively Regulated by miR129-5p in Laryngeal Squamous Cell Carcinoma

10.21203/rs.3.rs-21929/v1 ◽

2020 ◽

Author(s):

Xiu-Ping Tu ◽

Hao Li ◽

Liang-Si Chen ◽

Xiao-Ning Luo ◽

Zhong-Ming Lu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Tumor Growth ◽

Cell Carcinoma ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Migration And Invasion ◽

Tissue Samples ◽

Direct Target

Abstract Background Orthodenticle homeobox 1 (OTX1) is a transcription factor that plays important roles in various human cancers. However, the function of OTX1 in laryngeal squamous cell carcinoma (LSCC) is largely unknown. We aim to explore the roles of OTX1 in LSCC and possible molecular mechanism.Methods The expression levels of OTX1 were assessed in LSCC cell lines and tissue samples. We further examined the effect of OTX1 on LSCC progression. The upstream regulator of OTX1 was identified using computer algorithm and confirmed experimentally.Results OTX1 was highly expressed in 70.7% (70/99) of LSCC patient tissues. The OTX1 expression in LSCC was significantly correlated with lymph node metastasis. High OTX1 expression in LSCC patients was correlated with poor prognosis. Knockdown of OTX1 inhibits proliferation, colony formation, migration and invasion in LSCC cells. Knockdown of OTX1 inhibits tumor growth in a xenograft mouse model. Mechanistically, OTX1 might act as a direct target of miR-129-5p. OTX1 enhances tumorigenicity and tumor growth both in vitro and in vivo.Conclusions Our findings support that OTX1 is an oncogene in LSCC tumorigenesis and progression. Furthermore, OTX1as a direct target of miR-129-5p in LSCC cells.Taken together, OTX1 is a promising diagnostic and therapeutic marker for LSCC.

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Huaier Inhibits Proliferation, Migration, and Invasion of Cutaneous Squamous Cell Carcinoma Cells by Inhibiting the Methylation Levels of CDKN2A and TP53

Integrative Cancer Therapies ◽

10.1177/15347354211031646 ◽

2021 ◽

Vol 20 ◽

pp. 153473542110316

Author(s):

Liang Wang ◽

Lei Xu ◽

Yu Wang

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Dna Methyltransferase ◽

Cutaneous Squamous Cell Carcinoma ◽

Migration And Invasion ◽

Dependent Manner ◽

Concentration Gradients ◽

A431 Cells

Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor that originates from keratinocytes in the epidermis or appendage. Traditional Chinese medicine Huaier has anti-tumor activity in various malignancies. Little is known about the role of Huaier in CSCC. Here, we investigated the function of Huaier in CSCC. We treated CSCC cell line (SCL-1 and A431) with a series of concentration gradients of Huaier to examine the half maximal inhibitory concentration (IC50) of Huaier on SCL-1 and A431 cells. The IC50 of Huaier on growth of SCL-1 and A431 cells were 6.96 and 7.57 mg/mL, respectively. Moreover, Huaier reduced the methylation levels of CDKN2A and TP53, and enhanced the expression of CDKN2A and TP53 in SCL-1 and A431 cells in a dosage-dependent manner. The expression of DNA methyltransferase DNMT1 was severely repressed by Huaier treatment in SCL-1 and A431 cells. DNMT1 overexpression enhanced the methylation levels of CDKN2A and TP53, and suppressed the expression of CDKN2A and TP53 in Huaier-treated SCL-1 and A431 cells. Huaier treatment inhibited proliferation, migration, and invasion of SCL-1 and A431 cells. However, inhibition of CDKN2A or TP53 reversed the influence of Huaier treatment on proliferation, migration, and invasion of CSCC cells. In conclusion, our data demonstrate that Huaier inhibits proliferation, migration, and invasion of CSCC cells by regulating DNA methylation of CDKN2A and TP53, thereby attenuating the progression of CSCC. Thus, Huaier extract may act as a drug for treating CSCC.

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