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Identification of a hypoxia-suppressed lncRNA RAMP2-AS1 in breast cancer
Weiyang Lou1, Shuyuan Xiao2, Kuailu Lin3
1Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
Non-Coding RNA Research
|April 9, 2024
Summary
This study identifies RAMP2-AS1 as a key long non-coding RNA (lncRNA) suppressed by hypoxia in breast cancer. It reveals RAMP2-AS1
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Hypoxia is a critical hallmark of solid tumors, significantly influencing cancer progression, including breast cancer.
- The intricate interplay between long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in hypoxia-driven breast cancer remains incompletely understood.
- Understanding these regulatory networks is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To construct a hypoxia-related lncRNA-miRNA-mRNA regulatory network in breast cancer using computational analyses.
- To identify key lncRNAs, miRNAs, and genes involved in the hypoxia-mediated progression of breast cancer.
- To elucidate the regulatory role of RAMP2-AS1 in breast cancer under hypoxic conditions.
Main Methods:
- Utilized in silico analyses and integrated public databases to build a competing endogenous RNA (ceRNA) network.
- Performed single-cell resolution analysis to identify hypoxia-associated regulatory interactions.
- Conducted survival analysis and in vitro experiments to validate key findings.
Main Results:
- Identified RAMP2-AS1 as a significantly downregulated lncRNA in breast cancer, negatively correlated with hypoxia and associated with favorable prognosis.
- Discovered miR-660-5p, miR-2277-5p, and miR-1301-3p as upregulated downstream miRNAs of RAMP2-AS1 with poor prognostic value.
- Screened ATM and MYH11 as potential downstream hypoxia-related genes regulated by the RAMP2-AS1/miRNA axis, with in vitro validation of the RAMP2-AS1/miR-660-5p/ATM pathway.
Conclusions:
- Elucidated RAMP2-AS1 as a crucial hypoxia-suppressed lncRNA in breast cancer.
- Established a potential regulatory mechanism involving RAMP2-AS1, its downstream miRNAs (miR-660-5p), and target genes (ATM) in breast cancer progression under hypoxia.
- Highlighted RAMP2-AS1 as a potential prognostic biomarker and therapeutic target for breast cancer.
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