MALAT1 overexpression contributes to choriocarcinoma by binding with RBM10 and promoting p53 degradation.

BACKGROUND

Choriocarcinoma (CC), a highly aggressive and malignant subtype of gestational trophoblastic disease (GTD), arises from the dysregulated proliferation of trophoblastic cells, which normally mediate placental development during pregnancy. This study aimed to characterize the expression and functional significance of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a nuclear-enriched long non-coding RNA, in CC pathogenesis.

METHODS

We analyzed MALAT1 expression levels in 30 normal placental villi, 46 hydatidiform moles (repressive subtype), and 52 CC specimens. To identify MALAT1-interacting proteins, we performed RNA antisense purification followed by immunoblotting, with subsequent validation via co-immunoprecipitation (Co-IP) and immunofluorescence (IF) assays.

RESULTS

MALAT1 was significantly upregulated in CC tissues compared to controls. In vivo xenograft experiments further revealed that MALAT1 overexpression enhanced tumor growth. Mechanistically, we identified RNA-binding motif protein 10 (RBM10), a key spliceosomal regulator, as a novel MALAT1-binding partner. Strikingly, MALAT1 promoted p53 protein degradation without affecting its transcriptional levels, and this oncogenic effect was mediated through an RBM10-dependent mechanism.

CONCLUSIONS

In conclusion, our findings establish MALAT1 as a critical oncogenic driver in CC, functioning through its interaction with RBM10 to destabilize p53 and accelerate tumor progression. These insights highlight the potential of the MALAT1-RBM10-p53 axis as a therapeutic target in CC.