hsa_circ_0005358 suppresses cervical cancer metastasis by interacting with PTBP1 protein to destabilize CDCP1 mRNA

Abstract

Metastasis is the main cause of cervical cancer lethality, but to date, no effective treatment has been developed to block metastasis. Circular RNAs (circRNAs) were recently found to be involved in cancer metastasis. In this study, we identified a downregulated circRNA derived from the host gene Gli1 (hsa_circ_0005358) in cervical cancer tissues, which was expressed at lower levels in tissues with extracervical metastasis than in those without extracervical metastasis. Upregulation of hsa_circ_0005358 significantly suppressed the migration and invasion of cervical cancer cells in vitro , and downregulation of hsa_circ_0005358 had the opposite effect. A mouse model revealed that cervical cancer cells overexpressing hsa_circ_0005358 possessed weaker metastatic potential in vivo . RNA-pull-down assay, mass spectrometry, and RNA immunoprecipitation validated the findings that hsa_circ_0005358 functions via its 215–224 sequence, which interacts with polypyrimidine tract-binding protein 1 (PTBP1). RNA-sequencing profiling revealed that CUB-domain-containing protein 1 (CDCP1) is a common target for hsa_circ_0005358 and PTBP1. We further confirmed that hsa_circ_0005358 sequestered PTBP1, preventing it from stabilizing CDCP1 mRNA, reducing CDCP1 protein translation and ultimately suppressing cancer metastasis. Our findings reveal the function of hsa_circ_0005358 in tumor metastasis, which may be applied to a potential therapeutic approach for patients with metastatic cervical cancer.

LncRNA SFTA1P promotes cervical cancer progression by interaction with PTBP1 to facilitate TPM4 mRNA degradation

“…PTBP1 is a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family, which is involved in splicing regulation, IRES-mediated translation initiation, and mRNA stability [13,40,41,44]. It has been reported to be up-regulated to exert tumor-promoting roles in a variety of cancers including cervical cancer [31][32][33][34][35]. However, the biological functions of PTBP1 in cervical cancer remains to be explored.…”

“…RNA extraction and RT-qPCR were conducted for each sample as previously described [ 34 , 48 ]. All primers are listed in Supplementary Table S1 .…”

“…The wound healing assays were performed by using culture-inserts (Ibidi GmbH, Munich, Germany) as described previously [ 34 ]. Cells were seeded in 70 μL medium at a density of 7 × 10 5 cells/mL (CaSki) and 10 × 10 5 cells/mL (C-4 I) on each side of the culture-inserts, into 12-well plate.…”

“…It has been previously reported that PTBP1 plays a tumorpromoting role in cancer progression [31][32][33] and is associated with cervical lesion progression and carcinogenesis in our former studies [34,35]. To find related downstream genes, we performed RNA-seq on SFTA1P knockdown cells (upper panel in Fig.…”

Oncogenic circTICRR suppresses autophagy via binding to HuR protein and stabilizing GLUD1 mRNA in cervical cancer

“…The specific probe targeting the back-splice junction of circTICRR was labeled with Cy3, and probe sequences are listed in Table S3 . The FISH assay was conducted as previously described [ 44 ].…”