CSE1L silence inhibits the growth and metastasis in gastric cancer by repressing GPNMB via positively regulating transcription factor MITF

2019/07/25 by Yijun Li, Shanshan Yuan, Jiaming Liu +4 · 38 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Biochemistry #Biology #Cancer research #Cell biology #Gene #Kinase #MAPK/ERK pathway #Medicine #MicroRNA in disease regulation #Microphthalmia-associated transcription factor #PI3K/AKT/mTOR pathway #Protein kinase A #Protein kinase B #RNA Research and Splicing #RNA modifications and cancer #Signal transduction #Transcription factor

paper · doi:10.1002/jcp.29107

published in Journal of Cellular Physiology 235(3), 2071-2079 (Wiley)

openalex publication_date 2019/07/25 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/27

Abstract

Human chromosomal segregation 1-like (CSE1L) gene functions as a key molecular mediator in cellular proliferation, invasion, and apoptosis. The association of CSE1L with tumor progression has been reported in diverse human cancers. A greater understanding of CSE1L molecular mechanism is beneficial for cancer treatment. In the current study, we show that CSE1L was highly expressed in gastric cancer (GC) cell lines. CSE1L silence promoted apoptosis and inhibited cell proliferation and invasion. Overexpression of glycoprotein nonmetastatic melanoma protein B (GPNMB) reversed the anticancer effect of CSE1L inhibition. CSE1L inhibition decreased GPNMB by microphthalmia-associated transcription factor (MITF). Moreover, GPNMB regulates the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway. Taken together, our study revealed that CSE1L inhibition decreased MITF and suppressed GPNMB expression, thereby activating the PI3K/Akt/mTOR and MEK/ERK signaling pathway, ultimately inhibiting the tumor growth and metastasis in GC.

Citations

• Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

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