PRPF6 promotes metastasis and paclitaxel resistance of ovarian cancer via SNHG16/CEBPB/GATA3 axis

Abstract

Metastasis and paclitaxel (PTX) resistance are the main reason for the poor prognosis of ovarian cancer (OC).Evidence showed that RNA-binding proteins (RBPs) and long noncoding RNAs (lncRNAs) can modulate posttranscriptional regulation. The aim of this study was to determine the relationship among RBP, lncRNA and OC and to further guide clinical therapy. Immunohistochemistry revealed that pre-mRNA processing factor 6 (PRPF6) was upregulated in OC chemoresistant tissues and was closely related to advanced (Federation of International of Gynecologists and Obstetricians) FIGO stages and chemo-resistance. PRPF6 promoted progression, and PTX resistance in vitro and in vivo. And the transcripts of small nucleolar RNA host gene SNHG16-L/S were differentially expressed in OC cells and tissues as detected through real-time PCR (RT-PCR). SNHG16-L/S had opposite effects on progression and PTX resistance in OC. Mechanistically, SNHG16-L inhibited GATA-binding protein 3 (GATA3) transcription by binding to CCAAT/enhancer-binding protein B (CEBPB). Moreover, PRPF6 induced the alternative splicing of SNHG16, causing downregulation of SNHG16-L and, leading to the upregulation of GATA3 expression to further promote metastasis and PTX-resistance in OC. Totally, these data unveiled that PRPF6 promotes metastasis and PTX resistance of OC through SNHG16-L/CEBPB/GATA3 axis, which provides a new direction for OC treatment.

Advances in the role of GPX3 in ovarian cancer (Review)

“…When GPX3 is inhibited by RNA interference, the sensitivity of clear cell adenocarcinoma cells to cisplatin increases. Following GPX3 inhibition, tumor cells may proliferate, enhancing drug accumulation within the cells (73,77).…”

“…Recently, the interest among researchers in the role of non-coding RNAs in the regulation of tumorigenesis and development is growing. Wang et al (77) conducted a study that focused on the small nuclear kernel RNA host gene 16 (SNHG16)/Enhancer binding protein β(CEBPB)/GATA3 axis and its influence on precursor mRNA processing factor 6 (PRPF6) and GATA3 expression. The findings of their study revealed that PRPF6 promotes the expression of GATA3 by inducing SNHG16 (77).…”

“…Wang et al (77) conducted a study that focused on the small nuclear kernel RNA host gene 16 (SNHG16)/Enhancer binding protein β(CEBPB)/GATA3 axis and its influence on precursor mRNA processing factor 6 (PRPF6) and GATA3 expression. The findings of their study revealed that PRPF6 promotes the expression of GATA3 by inducing SNHG16 (77). SNHG16 specifically interacts with CEBPB to upregulate the transcriptional activity of GATA3.…”