Abstract
BackgroundEndometrial 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.MethodsTumor 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.ResultsHsa_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.ConclusionOur 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 registrationNot Applicable.
Highlights
Endometrial cancer (EC) is a common gynecologic malignancy worldwide
The results showed that hsa_circ_0002577, hsa_circ_0005797, hsa_circ_0057780, and hsa_circ_0016595 were the top upregulated circular RNA (circRNA) between EC and noncancerous tissues (Fig. 1 a)
We measured the expressions of these circRNAs in 84 paired EC and normal tissue samples, and found that hsa_circ_0002577 was the most upregulated one in EC tissues (Fig. 1 b, Supplementary Figure 1A)
Summary
Endometrial cancer (EC) is a common gynecologic malignancy worldwide. Endometrial cancer (EC) is the fourth commonly diagnosed gynecologic malignancy worldwide with an annual increase in incidence of approximately 1–2% [1, 2]. Seventy-five percent patients are diagnosed at an early stage (I/II) and their overall 5-year survival rate was over 70%. The survival rates of women who are diagnosed at FIGO stage III or IV are 57–66% and 20–26%, respectively [5]. Surgeries include pelvic lymph node dissection, bilateral salpingo-oophorectomy, and hysterectomy remain as the mainstay of EC treatment for early diagnosed patients [6]. Several molecular targeted therapies for EC are currently under investigation, such as phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin inhibitors and epidermal growth factor receptor inhibitor [8, 9]. The identification of novel molecular targets facilitates the development of diagnostic and therapeutic approaches for EC patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
