Background: Endometrial cancer (EC) is a common gynecologic malignancy worldwide. This study investigated the regulatory effects of circular RNA (circRNA) hsa_circ_0002577 on the tumorigenesis of EC.
Methods: Tumor samples and adjacent normal tissues were obtained from 84 EC patients. Recombinant lentiviral vectors expressing hsa_circ_0002577 (Lv-circRNA), short hairpin RNAs against hsa_circ_0002577 (sh-circRNA), miR-625-5p mimics, miR-625-5p inhibitor, lentiviral vectors expressing insulin-like growth factor 1 receptor (IGF1R) and their corresponding controls were transfected into EC cells as designated. A mouse xenograft model was established in BALB/c mice by inoculating Ishikawa cells transfected with sh-circRNA or control sequence.
Results: Hsa_circ_0002577 was upregulated in EC tissue samples and cells as compared to normal controls. EC patients with higher expression of hsa_circ_0002577 showed poorer overall survival and more advanced tumor stage. EC cells transfected with Lv-circRNA showed promoted proliferation, migration, and invasion, whereas the delivery of sh-circRNA exerted an opposite effect. Further analyses showed that hsa_circ_0002577 acted as a miR-625-5p sponge in EC cells. IGF1R was a potential downstream target of miR-625-5p. The expression of IGF1R in EC tissues was significantly higher than that in matched controls. Hsa_circ_0002577 accelerated EC development by inducing IGF1R expression and activating PI3K/Akt signaling pathway. Also, the knockdown of hsa_circ_0002577 delayed tumor growth and metastasis in the inoculated mice.
Conclusion: Our study showed that circRNA hsa_circ_002577 accelerated EC progression by acting as a miR-625-5p sponge, upregulating IGF1R and activating the PI3K/Akt pathway, suggesting the potential therapeutic use of hsa_circ_002577 in EC treatment.
Trial registration: Not Applicable.
Keywords: Circular RNA; Endometrial cancer; IGF1R; PI3K/Akt pathway; miRNA sponge.