miR‑1299/NOTCH3/TUG1 feedback loop contributes to the malignant proliferation of ovarian cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Notch receptor 3 (NOTCH3) plays an oncogenic role in ovarian cancer (OC).
• The precise regulatory mechanisms of NOTCH3 in OC pathogenesis require further elucidation.
• Identifying novel regulators and pathways is crucial for developing targeted therapies.

Purpose of the Study:

• To identify microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate NOTCH3 in OC.
• To investigate the functional role of identified regulators in OC cell proliferation and tumor growth.
• To explore the underlying molecular mechanisms, including potential feedback loops, involving NOTCH3, miRNAs, and lncRNAs in OC.

Main Methods:

• Bioinformatics analysis and luciferase reporter assays to identify regulatory miRNAs and lncRNAs.
• In vitro assays (cell proliferation, colony formation, EdU incorporation, cell cycle analysis) to assess functional effects.
• In vivo xenograft mouse models to evaluate tumor growth suppression.

Main Results:

• MicroRNA-1299 (miR-1299) was identified as a direct negative regulator of NOTCH3, downregulated in OC.
• Overexpression of miR-1299 inhibited OC cell proliferation, colony formation, and induced G0G1 cell cycle arrest, suppressing tumor growth in vivo.
• Long non-coding RNA taurine upregulated gene 1 (TUG1) acts as a sponge for miR-1299, upregulating NOTCH3 and promoting proliferation.
• A feedback loop involving miR-1299, NOTCH3, and TUG1 was identified in OC development.

Conclusions:

• miR-1299 functions as a tumor suppressor in OC by targeting NOTCH3.
• The lncRNA TUG1 promotes OC progression via the competing endogenous RNA mechanism involving miR-1299 and NOTCH3.
• The identified miR-1299/NOTCH3/TUG1 feedback loop provides novel insights into OC pathogenesis and potential therapeutic strategies.