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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Downregulated m⁵C regulator NSUN6 enhances proliferation, migration and affects immune regulation in ovarian cancer
Kuan Hu1, Wenjing Shi2, Zongjiang Zhou2
1Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Abstract:
Ovarian cancer (OC) remains one of the most lethal gynecological malignancies, largely due to late diagnosis and high metastatic potential. RNA 5-methylcytosine (m⁵C) modification has emerged as a key regulatory mechanism in cancer biology, yet the role of m⁵C-related genes such as NSUN6 in OC remains poorly understood. In this study, we first obtained three OC datasets and one m5C-related dataset from the GEO database and identified differentially expressed genes (co-DEGs) using Venn diagram analysis. Kaplan Meier plotter showed that NSUN6 was the only regulator significantly associated with patient prognosis. Additionly, Western Blot, Online database analysis and immunohistochemical staining evaluation showed that NSUN6 was significantly downregulated in OC and negatively correlated with tumor stage, metastasis and survival. Next, we overexpressed NSUN6 in OC cell lines. CCK8, wound healing and Transwell assays demonstrated that NSUN6 overexpression inhibited OC cell proliferation, migration, and invasion. Rescue experiments confirmed NSUN6-mediated suppression of AKT phosphorylation. In vivo xenograft models confirmed the tumor-suppressive effect of NSUN6, showing reduced tumor burden in both intraperitoneal and subcutaneous models. Bioinformatic analyses revealed enrichment in immune-related pathways and correlations with immune infiltration markers, which were further validated using ovarian cancer clinical samples. Collectively, our results demonstrate that NSUN6 is downregulated in OC and suppresses OC proliferation, migration, and invasion by inhibiting AKT activity, highlighting its potential as a therapeutic target in OC.
Insights
The gene NSUN6 is downregulated in ovarian cancer (OC) and suppresses tumor growth and spread. Restoring NSUN6 may offer a new therapeutic strategy for OC patients.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Ovarian cancer (OC) is a lethal gynecological malignancy with late diagnosis and high metastatic potential.
- RNA 5-methylcytosine (m⁵C) modification is a key regulator in cancer, but the role of m5C-related genes like NSUN6 in OC is unclear.
Purpose of the Study:
- To investigate the role of NSUN6 in ovarian cancer progression and its potential as a therapeutic target.
Main Methods:
- Analysis of OC datasets from GEO database, Kaplan Meier plotter, Western Blot, immunohistochemical staining, cell line overexpression, CCK8, wound healing, Transwell assays, in vivo xenograft models, and bioinformatic analyses.
Main Results:
- NSUN6 was significantly downregulated in OC and correlated with poorer prognosis, advanced tumor stage, metastasis, and survival.
- NSUN6 overexpression inhibited OC cell proliferation, migration, and invasion by suppressing AKT phosphorylation.
- In vivo studies confirmed NSUN6's tumor-suppressive effects, and bioinformatic analysis indicated enrichment in immune-related pathways.
Conclusions:
- NSUN6 acts as a tumor suppressor in ovarian cancer by inhibiting AKT activity.
- NSUN6 downregulation contributes to OC progression, and NSUN6 represents a potential therapeutic target for OC.
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