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UBE2C mRNA expression controlled by miR-300 and HuR determines its oncogenic role in gastric cancer
Ying Wang1, Feifei Huang2, Ming Liu2
1State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Center for Translational Medicine, School of Life Sciences, Nanjing University, Nanjing, 210000, China; Department of Urology, University of California, San Francisco, San Francisco, CA, 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, 94158, USA.
Abstract:
Ubiquitin Conjugating Enzyme E2 C (UBE2C) has a key oncogenic role in many human malignancies, including gastric cancer. However, it remains largely unknow at which level UBE2C expression is altered, as well as what are the downstream targets of UBE2C. In this study, we show that UBE2C is frequently overexpressed in gastric cancer patients. Interestingly, high expression of UBE2C mRNA instead of genome amplification is the predominant alterations observed in both stomach adenocarcinoma. We then confirmed that silencing UBE2C not only suppresses gastric cancer colony formation, but also inhibits DNA biosynthesis. Furthermore, we discovered that microRNA-300 is able to suppress gastric cancer progression through reducing UBE2C mRNA abundance, which is protected by an RNA binding protein HuR. Lastly, through an analysis of genes whose expressions correlate with that of UBE2C from gastric cancer cell lines, we have proposed several key genes that can be regulated by UBE2C, contributing to its oncogenic activity.
Insights
Ubiquitin Conjugating Enzyme E2 C (UBE2C) is overexpressed in gastric cancer, primarily at the mRNA level. Suppressing UBE2C inhibits cancer growth and DNA synthesis, revealing potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ubiquitin Conjugating Enzyme E2 C (UBE2C) is implicated in oncogenesis across various human cancers.
- Understanding the precise mechanisms and regulatory pathways of UBE2C in gastric cancer is crucial for therapeutic development.
Purpose of the Study:
- To investigate the expression levels and alterations of UBE2C in gastric cancer.
- To identify downstream targets and regulatory mechanisms of UBE2C in gastric cancer progression.
- To explore the potential of targeting UBE2C for gastric cancer treatment.
Main Methods:
- Quantitative analysis of UBE2C expression in gastric cancer patients.
- Experimental manipulation of UBE2C levels (silencing) in gastric cancer cell lines.
- Assessment of DNA biosynthesis and colony formation assays.
- MicroRNA expression analysis and RNA binding protein interaction studies.
Main Results:
- UBE2C is frequently overexpressed in gastric cancer, predominantly via elevated mRNA levels rather than gene amplification.
- Silencing UBE2C significantly suppresses gastric cancer cell proliferation and inhibits DNA biosynthesis.
- MicroRNA-300 was identified as a suppressor of gastric cancer progression by reducing UBE2C mRNA abundance, with HuR protecting UBE2C mRNA.
- Several potential UBE2C-regulated genes contributing to its oncogenic activity were proposed based on expression correlation analysis.
Conclusions:
- Elevated UBE2C mRNA expression is a key driver of gastric cancer.
- Targeting UBE2C or its regulatory pathways, such as microRNA-300, holds promise for gastric cancer therapy.
- Further investigation into UBE2C-regulated genes may uncover novel therapeutic strategies.
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