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Transformer 2β regulates alternative splicing of cell cycle regulator genes to promote ovarian cancer cell progression

ABSTRACT: Poor prognosis of late stage ovarian cancer patients is observed with high metastasis rate, but the underlying molecular mechanism is ambiguous. RNA binding proteins (RBPs) play important roles in post-transcriptional regulation in tumor neoplasia and metastasis. In this study, we dedicated to explore the molecular functions of a canonical RBP, TRA2B, in cancer cells. By knocking TRA2B expression in HeLa cells and performing whole transcriptome sequencing experiment (RNA-seq), we found TRA2B-regulated alternative splicing profile was tightly associated with mitotic cell cycle, apoptosis, and several cancer pathways. Meanwhile, hundreds of genes were regulated by TRA2B at expression level, and their functions were enriched in cell proliferation, cell adhesion and angiogenesis, which were also related to cancer progression. We also observed the AS regulation and expression regulation were independent by integrating AS genes and expression changed genes. We then explored and validated the carcinogenic functions of TRA2B by knocking down its expression in ovarian cancer cells. In vivo, higher expression level of TRA2B was associated with poor prognosis in ovarian cancer patients. In conclusion, we demonstrated the important roles of TRA2B in ovarian cancer neoplasia and progression, and identified the underlying molecular mechanisms, making a contribution to molecular targeting treatment of ovarian cancer in the future.

ORGANISM(S): Homo sapiens

PROVIDER: GSE176214 | GEO | 2023/08/16

REPOSITORIES: GEO

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