Tumor cells-derived extracellular vesicles carry circ_0064516 competitively inhibit microRNA-6805-3p and promote cervical cancer angiogenesis and tumor growth

ABSTRACT

Background

The current study tried to elucidate the regulatory role of tumor cell-derived exosomes (Exos)-circ_0064516 in angiogenesis and growth of cervical cancer.

Research design and methods

Related cirRNAs and downstream target genes were identified through bioinformatics analysis. Exos were isolated from cervical cancer cell line CaSki, followed by co-cultured with human umbilical vein endothelial cells (HUVECs). Then, the roles of circ_0064516, miR-6805-3p, and MAPK1 in migration and angiogenesis of HUVECs were assayed. Furthermore, xenografted tumors were transplanted into nude mice for in vivo validation.

Results

In vitro assay validated highly expressed circ_0064516 in cervical cancer cells. Tumor cell-derived Exos carried circ_0064516 to HUVECs. circ_0064516 increased MAPK1 expression by binding to miR-6805-3p, thus enhancing migration and angiogenesis. Exos containing circ_0064516 also promoted tumorigenesis of cervical cancer cells in nude mice.

Conclusions

We confirmed the oncogenic role of tumor cell-derived Exos carrying circ_0064516 in cervical cancer progression through miR-6805-3p/MAPK1.

KEYWORDS:

• Cervical cancer
• Angiogenesis
• circ_0064516
• miR-6805-3p
• MAPK1
• HUVECs
• tumor cell-derived exosomes
• ceRNA

Abbreviations

Exosomes (Exos), Circular RNAs (circRNAs), microRNA (miR), mitogen-activated protein kinase 1 (MAPK1), Gene Expression Omnibus (GEO), fold change (FC), HUVECs, Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), wild-type (WT), mutant type (MUT), RNA binding protein immunoprecipitation (RIP), Argonaute 2 (Ago2), Fluorescence in situ hybridization (FISH), Immunohistochemistry (IHC), microvessel density (MVD), microRNA(miR), U6 snRNA(U6), Streptavidin-Biotin Complex(SABC), 3,3N-Diaminobenzidine Tetrahydrochloride (DAB).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Ethics approval and consent to participate

This study was approved by the ethics committee of our hospital (No. SCXK2018–19). Animal experimentations were completed following the guidelines for the care and use of laboratory animals issued by the National Institutes of Health (NIH, Bethesda, Maryland, U.S.A.).

Data availability statement

The datasets generated and/or analyzed during the current study are available in the manuscript and supplementary materials.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14728222.2024.2306353.

Additional information

Funding

This study was funded by Sichuan Science and Technology Program [2023YFS0092].