LINC01234 coordinates protein interactions and ceRNA networks to enhance YWHAZ-driven malignancy in triple-negative breast cancer

Triple-negative breast cancer (TNBC) exhibits poor prognosis due to the lack of effective therapeutic targets. This study investigates the molecular mechanism of long non-coding RNA LINC01234 in TNBC progression. Our preliminary work identified significant upregulation of LINC01234 in TNBC cells, and its knockdown suppressed tumor progression. Here, through RNA-pulldown coupled with mass spectrometry, we screened LINC01234-interacting proteins and confirmed its direct binding to the scaffolding protein YWHAZ (14-3-3ζ) via RNA immunoprecipitation (RIP), which promotes YWHAZ phosphorylation. 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. These findings suggest a dual regulatory mechanism: LINC01234 directly activates YWHAZ's oncogenic function through protein interaction, while indirectly releasing the suppression of YWHAZ expression by sponging miR-204-5p. This study reveals a "protein interaction-ceRNA crosstalk" paradigm by which LINC01234 promotes TNBC progression, providing a theoretical foundation and potential therapeutic strategy for TNBC management.