Abstract
Circular RNAs (circRNAs) play essential roles in human bladder cancer (BCa) development, however, unusual expression patterns and functional dysfunction of circRNAs in BCa have not been evaluated. In this study, we validated that circKDM4C (hsa_circ_0001839), derived from the KDM4C gene, is elevated in BCa cell lines as well as tissues. Functionally, overexpression of circKDM4C significantly enhances, and silencing of circKDM4C suppresses migration and invasion capabilities of BCa cells. Mechanistically, circKDM4C can directly interact with miR-200b-3p and miR-200c-3p as a miRNA sponge, which enhances the expression of ZEB1 and promotes mesenchymal phenotype. Conclusively, our findings indicate that circKDM4C may act as a pro-oncogenic factor in BCa invasion and metastasis via the circKDM4C/miR-200bc-3p/ZEB1 axis, which is a potential biomarker or therapeutic target for bladder cancer.
Highlights
Bladder cancer (BCa) is the most prevalent malignant tumor in the urinary system
Elucidation of the mechanisms involved in BCa invasion and metastasis will inform the development of potential therapeutic strategies
We identified a KDM4C gene-derived circular RNA, termed circKDM4C, in which expression was remarkably elevated in BCa tissues and cell lines
Summary
Bladder cancer (BCa) is the most prevalent malignant tumor in the urinary system. Globally, it is the 10th most commonly clinically diagnosed cancer, with about 573,000 new cases and 213,000 deaths in 2020 [1]. We identified a KDM4C gene-derived circular RNA, termed circKDM4C, in which expression was remarkably elevated in BCa tissues and cell lines. RESULTS circKDM4C is elevated in BCa, and mainly distributes in the cytoplasm To explore the roles of circRNAs in bladder cancer progression, UM-UC3 and cisplatin-resistant UM-UC3 cells were screened for changes using RNA-seq, which found a lot of circRNAs associated with BCa cisplatin resistance and progression. The human KDM4C gene (GenBank: NM_015061) could generate 43 and 124 different circRNAs according to CircBase [20] and MiOncoCirc [7] database, respectively, and hsa_circ_0001839 consists of the exon 6, 7, and 8 (292 bp) (Fig. 1A). Hsa_circ_0001839 is the most abundant one of all KDM4C gene-derived circRNAs in various tumors shown in MiOncoCirc database (Fig. S1B).
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