Blockade of TRIM59 to enhance chemosensitivity of esophageal cancer cell to cisplatin by upregulating p53 expression.

e16509 Background: TRIM59 is the one of TRIM family characterized by an N-terminal really interesting new gene (RING)-finger domain, followed by two zinc-finger domains named B2 box and a coiled-coil (CC). Ubiquitination plays a vital role in the degradation of many kinds of proteins that function in the intracellular signaling pathway, cell cycle, DNA repair and transcriptional regulation. Because of the RING-finger domain, TRIM59 protein functions as E3 ubiquitin ligase activity and can selectively target ubiquitin-modified proteins for proteasomes or degradation. In additional, accumulating finding results have shown the TRIM proteins promote positively or negatively carcinogenesis. Here we focus on the TRIM59 protein: oncogenic activity in the promoting proliferation and metastasis of esophageal cancer cell. Methods: None. Results: Human esophageal cancer cells’ motility adopts various modes resulting in the HESC progression and poor survival of patients. We proved that TRIM59 is aberrantly up-regulated in metastatic human esophageal cancer (hESC) than adjacent normal esophageal tissue, which is on behalf of poor survival and advanced TNM state among the hESC patients. At the molecular level, we proved TRIM59 as an E3 putative ubiquitin ligase targets the p53 protein leading to the increased degradation of p53 resulting in the less chemotherapy sensitivity to cisplatin. TRIM59 knockdown in hESC cell lines reduced TRIM59 expression and promotes p53 protein level and decreased the proliferation, clone formation, migration. At the same time, hESC cell lines showed more sensitive to the cisplatin in the cell line treated with knockdown of TRIM59. These findings establish the relationship between TRIM59 and p53 and chemotherapy sensitivity of cisplatin and TRIM59 may be a promising prognostic indicator for esophageal squamous cell carcinoma (ESCA) patients. Conclusions: We have confirmed that the up-regulation of TRIM59 in human esophageal cancer tissues closely correlates with poor prognosis of patients and TRIM59 serves as an oncogene promoting the proliferation and metastasis of esophageal cancer. The study demonstrates that knockdown of TRIM59 inhibited the growth and invasion of Eca109 cancer cells and strengthened the chemosensitivity to cisplatin through the mechanism of increasing the p53 expression. These results suggest that combination of TRIM59 knockdown with cisplatin might provide a promising strategy to treat the patients with esophageal cancer.

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Synergistic Antiproliferative Effect in Combination Therapy of Δ12-Prostaglandin J2 and Hyperthermia-An in vitro Study with Human Esophageal Cancer Cell Lines

The Japanese Journal of Gastroenterological Surgery ◽

10.5833/jjgs.28.749 ◽

1995 ◽

Vol 28 (3) ◽

pp. 749-749

Author(s):

Tomohiro Saito ◽

Yoshinobu Yokoyama ◽

Toru Yunoki ◽

Mitsukazu Saito ◽

Yoshiaki Karaki ◽

...

Keyword(s):

Esophageal Cancer ◽

Combination Therapy ◽

Cell Lines ◽

Cancer Cell ◽

In Vitro Study ◽

Cancer Cell Lines ◽

Antiproliferative Effect ◽

Esophageal Cancer Cell ◽

Human Esophageal Cancer

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MiR-195-5p Reduces Esophageal Cancer Cell Proliferation Through The IGF-1R/AKT Axis

10.21203/rs.3.rs-569371/v1 ◽

2021 ◽

Author(s):

Zhao-xian Lin ◽

Xing Lin ◽

Lihuan Zhu ◽

Jian-yuan Huang ◽

Yang-yun Huang

Keyword(s):

Esophageal Cancer ◽

Lactate Production ◽

Cancer Cell Proliferation ◽

Poor Survival ◽

Atp Production ◽

Downstream Target ◽

Glut1 Expression ◽

Esophageal Cancer Cell ◽

Low Levels ◽

Novel Target

Abstract Background Esophageal cancer (ECa) remains a major cause of mortality across the globe. The expression of MiR-195-5p is altered in a plethora of tumors, but its role in ECa development and progression are undefined. Result Here, we show that miR-195-5p is downregulated in ECa and associated with poor survival in ECa. Function assays indicated that MiR-195-5p inhibited ECa progression. Mechanistically, we identified IGF-1R as a downstream target of miR-195-5p, and miR-195-5p/IGFR axis caused a loss of GLUT1 expression, reduced glucose uptake, reduced lactate production, and low levels of ATP production. Conclusion Collectively, miR-195-5p as a Eca suppressor impaired glycolysis. This highlighting miR-195-5p as a novel target for much needed anti-ECa therapeutics.

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MdmX Protects p53 from Mdm2-Mediated Degradation

Molecular and Cellular Biology ◽

10.1128/mcb.20.3.1001-1007.2000 ◽

2000 ◽

Vol 20 (3) ◽

pp. 1001-1007 ◽

Cited By ~ 142

Author(s):

Mark W. Jackson ◽

Steven J. Berberich

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Nuclear Export ◽

P53 Protein ◽

Ring Finger ◽

Ring Finger Domain ◽

Cycle Arrest ◽

Dependent Cell ◽

Potential Basis ◽

P53 Tumor Suppressor Protein

ABSTRACT The p53 tumor suppressor protein is stabilized in response to cellular stress, resulting in activation of genes responsible for either cell cycle arrest or apoptosis. The cellular pathway for releasing normal cells from p53-dependent cell cycle arrest involves the Mdm2 protein. Recently, a p53-binding protein with homology to Mdm2 was identified and called MdmX. Like Mdm2, MdmX is able to bind p53 and inhibit p53 transactivation; however, the ability of MdmX to degrade p53 has yet to be examined. We report here that MdmX is capable of associating with p53 yet is unable to facilitate nuclear export or induce p53 degradation. In addition, expression of MdmX can reverse Mdm2-targeted degradation of p53 while maintaining suppression of p53 transactivation. Using a series of MdmX deletions, we have determined that there are two distinct domains of the MdmX protein that can stabilize p53 in the presence of Mdm2. One domain requires MdmX interaction with p53 and results in the retention of both proteins within the nucleus and repression of p53 transactivation. The second domain involves the MdmX ring finger and results in stabilization of p53 and an increase in p53 transactivation. The potential basis for stabilization and increased p53 transactivation by the MdmX ring finger domain is discussed. Based on these observations, we propose that the MdmX protein may function to maintain a nuclear pool of p53 protein in undamaged cells.

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