miR-29b-3p Increases Radiosensitivity in Stemness Cancer Cells via Modulating Oncogenes Axis

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Cancer stem cells (CSCs) drive radioresistance, hindering radiotherapy success.
• MicroRNAs (miRNAs) are implicated in regulating cancer cell radiosensitivity.
• Three-dimensional (3D) cell culture models effectively mimic in vivo tumor microenvironments and induce CSC properties.

Purpose of the Study:

• To investigate the role of miRNAs in the radiosensitivity of 3D-cultured stem-like cells.
• To identify specific miRNAs that influence radioresistance in cancer models.
• To explore the therapeutic potential of miRNAs in enhancing radiotherapy efficacy.

Main Methods:

• Utilized miRNA microarray analysis to compare miRNA expression in 2D and 3D cell cultures.
• Analyzed The Cancer Genome Atlas (TCGA) database for clinical data correlation.
• Performed experiments involving miR-29b-3p overexpression and knockdown in 3D cultures and in vivo models.
• Assessed effects on DNA damage repair, oncogene expression, stemness, invasion, and migration.

Main Results:

• miR-29b-3p expression was significantly downregulated in 3D cultured cancer cells (A549, MCF7) compared to 2D cultures.
• High miR-29b-3p expression correlated with better prognosis in lung adenocarcinoma and breast invasive carcinoma patients.
• Overexpression of miR-29b-3p reduced radioresistance in 3D cultures and in vivo, by interfering with DNA repair and inhibiting oncogenes (RBL1, PIK3R1, AKT2, Bcl-2).
• miR-29b-3p knockdown increased cancer cell invasion and migration, while its overexpression reduced stemness properties.

Conclusions:

• miR-29b-3p acts as a radiosensitizer in CSC-like cells by suppressing oncogene expression.
• miR-29b-3p demonstrates potential as a novel therapeutic target to enhance radiotherapy outcomes.
• Restoring miR-29b-3p levels could be a promising strategy to overcome treatment resistance in cancer.