534 Fra-1 is an independent prognostic factor in esophageal squamous cell carcinoma and related to cell proliferation, migration and invasion in vitro

Abstract Background In recent years, long non-coding RNAs (lncRNAs) are of great importance in development of different types of tumors, while the function of lncRNA ZFAS1 is rarely discussed in esophageal squamous cell carcinoma (ESCC). Therefore, we performed this study to explore the expression of exosomal lncRNA ZFAS1 and its molecular mechanism on ESCC progression. Methods Expression of ZFAS1 and miR-124 in ESCC tissues was detected. LncRNA ZFAS1 was silenced to detect its function in the biological functions of ESCC cells. A stable donor and recipient culture model was established. Eca109 cells transfected with overexpressed and low expressed ZFAS1 plasmid and miR-124 inhibitor labeled by Cy3 were the donor cells, and then co-cultured with recipient cells to observe the transmission of Cy3-ZFAS1 between donor cells and recipient cells. The changes of cell proliferation, apoptosis, invasion, and migration in recipient cells were detected. The in vivo experiment was conducted for verifying the in vitro results. Results LncRNA ZFAS1 was upregulated and miR-124 was down-regulated in ESCC tissues. Silencing of ZFAS1 contributed to suppressed proliferation, migration, invasion and tumor growth in vitro and induced apoptosis of ESCC cells. LncRNA ZFAS1 was considered to be a competing endogenous RNA to regulate miR-124, thereby elevating STAT3 expression. Exosomes shuttled ZFAS1 stimulated proliferation, migration and invasion of ESCC cells and restricted their apoptosis with increased STAT3 and declined miR-124. Furthermore, in vivo experiment suggested that elevated ZFAS1-exo promoted tumor growth in nude mice. Conclusion This study highlights that exosomal ZFAS1 promotes the proliferation, migration and invasion of ESCC cells and inhibits their apoptosis by upregulating STAT3 and downregulating miR-124, thereby resulting in the development of tumorigenesis of ESCC.

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LncRNA JPX Promotes Esophageal Squamous Cell Carcinoma Progression by Targeting miR-516b-5p/VEGFA Axis

10.21203/rs.3.rs-798922/v1 ◽

2021 ◽

Author(s):

Yi He ◽

Bin Li ◽

Yang Yang ◽

Rong Hua ◽

Zhigang Li

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Fish Cell

Abstract Background: Long non-coding RNAs (lncRNAs) are reported act as important regulators in various cancers. LncRNA JPX was identified as an oncogenic regulator in lung cancer. However, the function of lncRNA JPX in the progression of esophageal squamous cell carcinoma (ESCC) remains unclear. Methods: The effects and molecular mechanism of JPX on the progression of ESCC were investigated using fluorescence in situ hybridization (FISH), cell proliferation, quantitative real-time PCR (qRT-PCR), western blot, dual luciferase, cell cycle, 5-Ethynyl-2′-Deoxyuridine (EdU) incorporation, transwell, RNA pull-down, tube formation and RNA immunoprecipitation (RIP) assays. Results: In the present study, we found JPX was highly expressed in tissues of ESCC patients and different ESCC cell lines. Functional assays demonstrated that JPX promoted ESCC cell proliferation, migration and invasion in vitro and tumor growth in vivo. Moreover, we found JPX promoted ESCC mobility in vitro. Mechanistically, the results showed that JPX functions as a sponge of miR-516b-5p, which targets an oncogene vascular endothelial growth factor A (VEGFA) in ESCC cells. Interactions between miR-516b-5p and JPX or VEGFA were confirmed by luciferase reporter assays. Furthermore, inhibition of JPX significantly attenuated the cell growth and mobility ability of ESCC cells in vitro. In addition, miR-516b-5p overexpression abrogated JPX enhanced proliferation, migration, invasion, and angiogenesis of ESCC cells. Conclusions: Our study demonstrated that JPX played an important role in promoting ESCC progression via the miR-516b-5p/VEGFA pathway and might serve as a promising novel therapeutic target for ESCC patients.

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Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway

Journal of Immunology Research ◽

10.1155/2020/6765474 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Jia-Huang Liu ◽

Qi-Fei Wu ◽

Jun-Ke Fu ◽

Xiang-Ming Che ◽

Hai-Jun Li

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Nude Mice ◽

Serum Glucose ◽

Migration And Invasion ◽

Endocrine Effect

Obesity could increase the risk of esophageal squamous cell carcinoma (ESCC) and affect its growth and progression, but the mechanical links are unclear. The objective of the study was to explore the impact of obesity on ESCC growth and progression utilizing in vivo trials and cell experiments in vitro. Diet-induced obese and lean nude mice were inoculated with TE-1 cells, then studied for 4 weeks. Serum glucose, insulin, leptin, and visfatin levels were assayed. Sera of nude mice were obtained and then utilized to culture TE-1. MTT, migration and invasion assays, RT-PCR, and Western blotting were used to analyze endocrine effect of obesity on cell proliferation, migration, invasion, and related genes expression of TE-1. Obese nude mice bore larger tumor xenografts than lean animals, and were hyperglycemic and hyperinsulinemic with an elevated level of leptin and visfatin in sera, and also were accompanied by a fatty liver. As for the subcutaneous tumor xenograft model, tumors were more aggressive in obese nude mice than lean animals. Tumor weight correlated positively with mouse body weight, liver weight of mice, serum glucose, HOMA-IR, leptin, and visfatin. Obesity prompted significant TE-1 cell proliferation, migration, and invasion by endocrine mechanisms and impacted target genes. The expression of AMPK and p-AMPK protein decreased significantly ( P < 0.05 ); MMP9, total YAP, p-YAP, and nonphosphorylated YAP protein increased significantly ( P < 0.05 ) in the cells cultured with conditioned media and xenograft tumor from the obese group; the mRNA expression of AMPK decreased significantly ( P < 0.05 ); YAP and MMP9 mRNA expression increased significantly ( P < 0.05 ) in the cells exposed to conditioned media from the obese group. In conclusion, the altered adipokine milieu and metabolites in the context of obesity may promote ESCC growth in vivo; affect proliferation, migration, and invasion of ESCC cells in vitro; and regulate MMP9 and AMPK-YAP signaling pathway through complex effects including the endocrine effect.

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THAP9-AS1/miR-133b/SOX4 positive feedback loop facilitates the progression of esophageal squamous cell carcinoma

Cell Death and Disease ◽

10.1038/s41419-021-03690-z ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Jiwei Cheng ◽

Haibo Ma ◽

Ming Yan ◽

Wenqun Xing

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Positive Feedback ◽

Feedback Loop ◽

Malignant Tumors ◽

Migration And Invasion ◽

Positive Feedback Loop

AbstractEsophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in the digestive system with a high incidence and poor prognosis. Long non-coding RNAs (LncRNA) have been reported to be closely associated with the occurrence and development of various human cancers. Data from GSE89102 shows an increase of THAP9-AS1 expression in ESCC. However, its functions and mechanisms underlying ESCC progression remain to be investigated. In this study, we found that THAP9-AS1 was overexpressed in ESCC tissues and cells. High THAP9-AS1 expression was positively correlated with tumor size, TNM stage, lymph node metastasis, and worse prognosis. Functionally, depletion of THAP9-AS1 suppressed cell proliferation, migration, and invasion, while enhanced apoptosis in vitro. Consistently, knockdown of THAP9-AS1 inhibited xenograft tumor growth in vivo. Mechanistically, THAP9-AS1 could serve as a competing endogenous RNA (ceRNA) for miR-133b, resulting in the upregulation of SOX4. Reciprocally, SOX4 bound to the promoter region of THAP9-AS1 to activate its transcription. Moreover, the anti-tumor property induced by THAP9-AS1 knockdown was significantly impaired due to miR-133b downregulation or SOX4 overexpression. Taken together, our study reveals a positive feedback loop of THAP9-AS1/miR-133b/SOX4 to facilitate ESCC progression, providing a potential molecular target to fight against ESCC.

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Cirsiliol targets tyrosine kinase 2 to inhibit esophageal squamous cell carcinoma growth in vitro and in vivo

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01903-z ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Xuechao Jia ◽

Chuntian Huang ◽

Yamei Hu ◽

Qiong Wu ◽

Fangfang Liu ◽

...

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Tumor Model ◽

Kinase Assay ◽

Tyrosine Kinase 2

Abstract Background Esophageal squamous cell carcinoma (ESCC) is an aggressive and lethal cancer with a low 5 year survival rate. Identification of new therapeutic targets and its inhibitors remain essential for ESCC prevention and treatment. Methods TYK2 protein levels were checked by immunohistochemistry. The function of TYK2 in cell proliferation was investigated by MTT [(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and anchorage-independent cell growth. Computer docking, pull-down assay, surface plasmon resonance, and kinase assay were used to confirm the binding and inhibition of TYK2 by cirsiliol. Cell proliferation, western blot and patient-derived xenograft tumor model were used to determine the inhibitory effects and mechanism of cirsiliol in ESCC. Results TYK2 was overexpressed and served as an oncogene in ESCC. Cirsiliol could bind with TYK2 and inhibit its activity, thereby decreasing dimer formation and nucleus localization of signal transducer and activator of transcription 3 (STAT3). Cirsiliol could inhibit ESCC growth in vitro and in vivo. Conclusions TYK2 is a potential target in ESCC, and cirsiliol could inhibit ESCC by suppression of TYK2.

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PS02.201: EXPRESSION AND ROLE OF CLIC1 IN HUMAN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Diseases of the Esophagus ◽

10.1093/dote/doy089.ps02.201 ◽

2018 ◽

Vol 31 (Supplement_1) ◽

pp. 179-179

Author(s):

Toshiyuki Kobayashi ◽

Atsushi Shiozaki ◽

Hitoshi Fujiwara ◽

Hirotaka Konishi ◽

Yoshito Nako ◽

...

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Microarray Analysis ◽

Squamous Cell ◽

Migration And Invasion ◽

Poor Prognostic Factor ◽

Weak Expression

Abstract Background Recent studies have reported important roles for chloride intracellular channel 1 (CLIC1) in various cancers; however, its involvement in esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of the present study was to investigate the role of CLIC1 in human ESCC. Methods CLIC1 expression in human ESCC cell lines was analyzed by Western blotting. Knockdown experiments were conducted with CLIC1 siRNA, and their effects on cell proliferation, the cell cycle, apoptosis, migration, and invasion were analyzed. The gene expression profiles of cells were analyzed using a microarray analysis. An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy. Results ESCC cells strongly expressed CLIC1. The depletion of CLIC1 using siRNA inhibited cell proliferation, induced apoptosis, and promoted cell migration and invasion. The results of the microarray analysis revealed that the depletion of CLIC1 regulated apoptosis via the TLR2/JNK pathway. Immunohistochemistry showed that CLIC1 was present in the cytoplasm of carcinoma cells, and that the very strong or very weak expression of CLIC1 was an independent poor prognostic factor. Conclusion The present results suggest that the very strong expression of CLIC1 enhances tumor survival, while its very weak expression promotes cellular movement. The present study provides an insight into the role of CLIC1 as a switch among tumor behaviors in ESCC. Disclosure All authors have declared no conflicts of interest.

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LncRNA GHET1 Promotes Esophageal Squamous Cell Carcinoma Cells Proliferation and Invasion via Induction of EMT

The International Journal of Biological Markers ◽

10.5301/ijbm.5000304 ◽

2017 ◽

Vol 32 (4) ◽

pp. 403-408 ◽

Cited By ~ 22

Author(s):

Hongfen Liu ◽

Qiang Zhen ◽

Yakun Fan

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Noncoding Rna ◽

In Vitro Assays ◽

Migration And Invasion ◽

Advanced Tumor

Background Recent studies have shown that long noncoding RNA (IncRNA) gastric carcinoma highly expressed transcript 1 (GHET1) was involved in the progression of tumors. However, the role of GHET1 in esophageal squamous cell carcinoma (ESCC) remains unclear. Methods The expression of IncRNA GHET1 was examined in 55 paired ESCC tissues and adjacent nontumor tissues. Molecular and cellular techniques were used to explore the role of GHET1 on ESCC cells. Results Our data showed that GHET1 expression was significantly increased in ESCC tissues and cell lines. High GHET1 expression in ESCC tissues was significantly associated with poor differentiation, advanced tumor nodes metastasis stage, and lymph node metastasis. GHET1 showed high sensitivity and specificity for diagnosing ESCC. Our data from in vitro assays showed that GHET1 inhibition suppressed ESCC cells proliferation, migration, and invasion, and induced cells apoptosis. Furthermore, western blot showed that GHET1 inhibition significantly decreased the expression of vimentin and N-cadherin while it increased the expression of E-cadherin. Conclusions Our study indicates that GHET1 acts as an oncogene in ESCC and may represent a novel therapeutic target for the treatment of ESCC patients.

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Long Non-Coding RNA CCAT2 Promotes the Development of Esophageal Squamous Cell Carcinoma by Inhibiting miR-200b to Upregulate the IGF2BP2/TK1 Axis

Frontiers in Oncology ◽

10.3389/fonc.2021.680642 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiaodan Wu ◽

Yihui Fan ◽

Yupeng Liu ◽

Biao Shen ◽

Haimin Lu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Clinical Samples ◽

Non Coding Rna

Long non-coding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). In the current study, we identified CCAT2 as a relevant lncRNA and investigated its role in the progression of ESCC. RT-qPCR was adopted to detect CCAT2 expression in collected clinical samples, ESCC cell lines, and a normal cell line. We tested the correlation between CCAT2 expression and the prognosis of ESCC. RT-qPCR or immunoblotting was adopted to detect the expression of relevant factors in ESCC tissues or cells. Cell proliferation, apoptosis, migration, and invasion were examined by colony formation assay, flow cytometry, scratch assay, and Transwell assay, respectively, while subcutaneous tumorigenesis in nude mice was adopted to examine the role of CCAT2 in tumorigenesis of ESCC cells in vivo. Bioinformatics analysis, dual luciferase reporter assay, and RIP were conducted for the target relationship profiling. Me-RIP was adopted to detect m6A modification level of TK1 in ESCC tissues or cells. Upregulated CCAT2, IGF2BP2, and TK1 expression and inhibited miR-200b expression were observed in ESCC cells and tissues. CCAT2 bound to miR-200b and reduced its expression, leading to upregulated IGF2BP2 expression. IGF2BP2 improved TK1 mRNA stability to enhance its expression by recognizing its m6A modification. CCAT2 promoted the migration and invasion of ESCC cells in vitro, and tumorigenesis in vivo by upregulating TK1 expression, while overexpression of miR-200b reversed these effects of CCAT2. Overall, this study suggests that CCAT2 competitively binds to miR-200b to alleviate its inhibitory effects on IGF2BP2 expression, resulting in elevated TK1 expression, and an ensuing promotion of the development of ESCC.

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