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Published on: March 27, 2020
LINC01234 Coordinates Protein Interactions and ceRNA Networks to Enhance YWHAZ-Driven Malignancy in Triple-Negative
Diping Yu1, Li Chen2, Huimin Li2
1Department of Thyroid and Breast Surgery, Kunming University of Science and Technology Affiliated Puer City People's Hospital, Puer, China.
Background:
Triple-negative breast cancer (TNBC) lacks effective therapies. Long noncoding RNA LINC01234 is upregulated in TNBC and promotes progression, but its molecular mechanism requires elucidation.
Methods:
RNA-pulldown with mass spectrometry and RNA immunoprecipitation (RIP) identified LINC01234-interacting proteins. Clinical correlation, functional assays (proliferation, migration, apoptosis), and mechanistic studies involving miR-204-5p and YWHAZ knockdown were performed.
Results:
LINC01234 directly binds to and promotes phosphorylation of the scaffolding protein YWHAZ (14-3-3ζ). Clinical analysis showed that YWHAZ was highly expressed in TNBC tissues and correlated with poor patient prognosis. Mechanistically, LINC01234 regulated YWHAZ expression via targeting miR-204-5p, thereby influencing tumor progression. Further functional validation demonstrated that either miR-204-5p overexpression or YWHAZ knockdown significantly inhibited TNBC cell proliferation/migration and promoted apoptosis.
Conclusion:
LINC01234 promotes TNBC progression through a dual "protein interaction-ceRNA crosstalk" mechanism, directly enhancing YWHAZ function and indirectly increasing its expression via sponging miR-204-5p, providing a theoretical foundation and potential therapeutic strategy for TNBC treatment.
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