LINC01234 Coordinates Protein Interactions and ceRNA Networks to Enhance YWHAZ-Driven Malignancy in Triple-Negative...

Area of Science:

• Molecular Biology
• Oncology
• Genetics

Background:

• Triple-negative breast cancer (TNBC) remains a significant therapeutic challenge due to a lack of targeted treatments.
• Long noncoding RNA LINC01234 is frequently overexpressed in TNBC and contributes to its progression.
• The precise molecular mechanisms underlying LINC01234's role in TNBC require further investigation.

Purpose of the Study:

• To elucidate the molecular mechanism by which LINC01234 promotes TNBC progression.
• To identify key protein and RNA interactions involving LINC01234 in TNBC.
• To evaluate the therapeutic potential of targeting the LINC01234 pathway in TNBC.

Main Methods:

• RNA-pulldown coupled with mass spectrometry and RNA immunoprecipitation (RIP) to identify LINC01234-interacting proteins.
• Functional assays including proliferation, migration, and apoptosis assays in TNBC cells.
• Mechanistic studies involving knockdown of miR-204-5p and YWHAZ, and clinical correlation analysis.

Main Results:

• LINC01234 directly interacts with and promotes the phosphorylation of the scaffolding protein YWHAZ (14-3-3ζ).
• High YWHAZ expression in TNBC tissues correlates with poor patient prognosis.
• LINC01234 acts as a competing endogenous RNA (ceRNA) to sponge miR-204-5p, thereby upregulating YWHAZ expression and promoting TNBC progression.
• Overexpression of miR-204-5p or knockdown of YWHAZ significantly inhibited TNBC cell proliferation and migration while promoting apoptosis.

Conclusions:

• LINC01234 drives TNBC progression through a dual mechanism involving direct protein interaction with YWHAZ and ceRNA crosstalk with miR-204-5p.
• This dual mechanism enhances YWHAZ function and expression, contributing to tumor growth and survival.
• The LINC01234/miR-204-5p/YWHAZ axis represents a promising theoretical foundation and potential therapeutic strategy for TNBC treatment.