CircVPRBP inhibits nodal metastasis of cervical cancer by impeding RACK1 O-GlcNAcylation and stability.

ABSTRACT

Lymph node (LN) metastasis is one of the most malignant clinical features in patients with cervical cancer (CCa). Understanding the mechanism of lymph node metastasis will provide treatment strategies for patients with CCa. Circular RNAs (circRNA) play a critical role in the development of human cancers. However, the role and mechanism of circRNAs in lymph node metastasis remain largely unknown. Here, it is reported that loss expression of circRNA circVPRBP was closely associated with LN metastasis and poor survival of CCa patients. In vitro and in vivo assays showed that circVPRBP overexpression notably inhibited lymphangiogenesis and LN metastasis, whereas RfxCas13d mediated silencing of circVPRBP promoted lymphangiogenesis and the ability of the cervical cancer cells to metastasize to the LNs. Mechanistically, circVPRBP could bind to RACK1 and shield the S122 O-GlcNAcylation site to promote RACK1 degradation, resulting in inhibition of Galectin-1 mediated lymphangiogenesis and LN metastasis in CCa. Taken together, the results demonstrate that circVPRBP is a potential prognostic biomarker and a novel therapeutic target for LN metastasis in CCa patients.