Deregulated HOXB7 Expression Predicts Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma and Regulates Cancer Cell Proliferation In Vitro and In Vivo

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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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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Prostaglandin E2 produced by inducible COX-2 and mPGES-1 promoting cancer cell proliferation in vitro and in vivo

Life Sciences ◽

10.1016/j.lfs.2014.07.042 ◽

2014 ◽

Vol 116 (1) ◽

pp. 43-50 ◽

Cited By ~ 37

Author(s):

Diana Ruan ◽

Shui-Ping So

Keyword(s):

Cell Proliferation ◽

Prostaglandin E2 ◽

Cancer Cell ◽

Cancer Cell Proliferation ◽

Cox 2 ◽

Proliferation In Vitro

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Exosomal lncRNA ZFAS1 regulates esophageal squamous cell carcinoma cell proliferation, invasion, migration and apoptosis via microRNA-124/STAT3 axis

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1473-8 ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 18

Author(s):

Zhirong Li ◽

Xuebo Qin ◽

Wei Bian ◽

Yishuai Li ◽

Baoen Shan ◽

...

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Tumor Growth ◽

Cell Carcinoma ◽

Squamous Cell ◽

Migration And Invasion ◽

Donor Cells

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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MiR-346-5p promotes colorectal cancer cell proliferation in vitro and in vivo by targeting FBXL2 and activating the β-catenin signaling pathway

Life Sciences ◽

10.1016/j.lfs.2020.117300 ◽

2020 ◽

Vol 244 ◽

pp. 117300 ◽

Cited By ~ 1

Author(s):

Shuang Pan ◽

Wei Wu ◽

Fu Ren ◽

Lei Li ◽

Yao Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Cancer Cell ◽

Colorectal Cancer Cell ◽

Cancer Cell Proliferation ◽

Proliferation In Vitro

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Bauhinia acuminata L. attenuates lung cancer cell proliferation: in vitro, in vivo and in silico approaches

Phytomedicine Plus ◽

10.1016/j.phyplu.2021.100173 ◽

2021 ◽

pp. 100173

Author(s):

Divya Sebastian ◽

K. Gowrishankar ◽

S. Ignacimuthu ◽

A.J. Renilda Sophy ◽

R. Vidhya ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cancer Cell ◽

In Silico ◽

Cancer Cell Proliferation ◽

Lung Cancer Cell ◽

Proliferation In Vitro

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LncRNA MTX2-6 Suppresses Cell Proliferation by Acting as ceRNA of miR-574-5p to Accumulate SMAD4 in Esophageal Squamous Cell Carcinoma

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.654746 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jie Li ◽

Xu Han ◽

Yan Gu ◽

Jixiang Wu ◽

Jianxiang Song ◽

...

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Molecular Mechanisms ◽

Non Coding Rna ◽

Long Non Coding Rna

Esophageal squamous cell carcinoma (ESCC) has been one of the key causes of cancer deaths worldwide. It has been found that long non-coding RNA (lncRNA) is related to the generation and progression of various cancers (including ESCC). However, there are still many lncRNAs related to ESCC whose functions and molecular mechanisms have not been clearly elucidated. In this study, we first reported that lncRNA MTX2-6 was significantly downregulated in ESCC tissues and cell lines. The decreased expression of MTX2-6 is closely related to larger tumor and worse prognosis of ESCC patients. Through a series of functional experiments, we detected that overexpressed MTX2-6 inhibited cell proliferation and promoted cell apoptosis of ESCC in vitro and in vivo. Further studies showed that MTX2-6 exerts as a competing endogenous RNA (ceRNA) by binding miR-574-5p and elevates the expression of SMAD4 in ESCC. In summary, our results clarify the tumor suppressor roles of MTX2-6/miR-574-5p/SMAD4 axis in the progression of ESCC and provide emerging therapeutic targets for ESCC patients.

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