CircINTS4 Facilitates Chemoresistance of TNBC by Competitively Binding miR-129-5p/POM121 Axis

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
• Circular RNAs (circRNAs) are emerging as key regulators in cancer development and progression.
• Understanding the role of specific circRNAs in TNBC is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the expression of circRNA circINTS4 in TNBC.
• To analyze the association between circINTS4 expression and clinicopathological characteristics and chemotherapy resistance in TNBC patients.
• To elucidate the molecular mechanism underlying circINTS4's role in TNBC.

Main Methods:

• Bioinformatics analysis to predict interactions between circINTS4, miR-129-5p, and POM121.
• Dual luciferase reporter assays to confirm binding interactions.
• RNA immunoprecipitation (RIP) and RNA pull-down assays to validate circRNA-miRNA binding.
• Quantitative real-time PCR (qRT-PCR) to assess expression levels.
• In vitro and in vivo experiments involving circINTS4 knockdown and manipulation of miR-129-5p/POM121 axis.

Main Results:

• CircINTS4 was significantly upregulated in Adriamycin-resistant TNBC cells.
• circINTS4 knockdown suppressed TNBC cell proliferation, migration, invasion, and autophagy.
• circINTS4 acts as a competing endogenous RNA (ceRNA) by sponging miR-129-5p, leading to POM121 upregulation.
• circINTS4 knockdown inhibited ADR-resistant TNBC tumor growth in vivo via the miR-129-5p/POM121 axis.

Conclusions:

• CircRNA circINTS4 promotes TNBC progression and chemoresistance by regulating the miR-129-5p/POM121 axis.
• circINTS4 serves as a ceRNA for miR-129-5p, upregulating its target gene POM121.
• circINTS4 represents a potential novel molecular target for clinical diagnosis and therapeutic strategies against TNBC drug resistance.