TRIM59 Promotes Retinoblastoma Progression by Activating the p38-MAPK Signaling Pathway.

Abstract

Purpose:

Retinoblastoma is a malignant tumor of the developing retina that mostly occurs in children. Our study aimed to investigate the effect of tripartite motif-containing protein 59 (TRIM59) on retinoblastoma growth and the underlying mechanisms.

Methods:

We performed bioinformatic analysis of three datasets (GSE24673, GSE97508, and GSE110811) from the Gene Expression Omnibus database. Quantitative reverse-transcription PCR and immunoblotting of three retinoblastoma cell lines were conducted to verify TRIM59 as a differentially expressed gene. Specific siRNAs were used to inhibit TRIM59 expression in the HXO-Rb44 cell line. A lentiviral vector was transfected into the Y79 cell line to overexpress TRIM59. The effects of TRIM59 on retinoblastoma cell proliferation, cell cycling, and apoptosis were explored in vitro using the abovementioned cell lines. The effect of TRIM59 expression on retinoblastoma cell proliferation was evaluated in a mouse xenograft tumor model.

Results:

TRIM59 expression in three retinoblastoma cell lines was remarkably elevated compared with normal control. Knocking down TRIM59 expression remarkably suppressed cell proliferation and growth and promoted cell apoptosis in HXO-Rb44 cells, whereas TRIM59 overexpression promoted tumor progression in Y79 cells. Silencing TRIM59 also markedly inhibited in vivo tumor growth in the xenograft model. Mechanistic studies revealed that TRIM59 upregulated phosphorylated p38, p-JNK1/2, p-ERK1/2, and p-c-JUN expression in retinoblastoma cells. Notably, the p38 inhibitor SB203580 attenuated the effects of TRIM59 on cell proliferation, apoptosis, and the G1/S phase transition.

Conclusions:

TRIM59 plays an oncogenic role in retinoblastoma and exerts its tumor-promotive function by activating the p38-mitogen-activated protein kinase pathway.

• Authors: Chao Wu, Xue-Qin Shang, Zhi-Peng You, Qi-Fang Jin, Yu-Lan Zhang, Yue Zhou, Yue-Zhi Zhang, Ke Shi
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 61 Issue 10 Pg. 2 (08 03 2020) ISSN: 1552-5783 [Electronic] United States
• PMID: 32744597 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Intracellular Signaling Peptides and Proteins
• RNA, Small Interfering
• TRIM59 protein, human
• Tripartite Motif Proteins

Topics

• Animals
• Apoptosis
• Cell Cycle (physiology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Disease Models, Animal
• Disease Progression
• Gene Expression Regulation, Neoplastic (physiology)
• Genetic Vectors (genetics)
• Humans
• Immunohistochemistry
• Intracellular Signaling Peptides and Proteins (genetics)
• Lentivirus (genetics)
• MAP Kinase Signaling System (physiology)
• Mice, Nude
• Phosphorylation
• RNA, Small Interfering (genetics)
• Real-Time Polymerase Chain Reaction
• Retinal Neoplasms (genetics, metabolism, pathology)
• Retinoblastoma (genetics, metabolism, pathology)
• Signal Transduction (physiology)
• Tripartite Motif Proteins (genetics)
• Xenograft Model Antitumor Assays