Enhancement of circular RNA 0002577 in serum exosomes in patients with endometrial cancer accelerates disease progression via general transcription factor II-I repeat domain-containing 1 (GTF2IRD1).

Abstract

Objective: Uterine corpus endometrial carcinoma (UCEC) is a common gynecologic malignancy with poor prognosis in advanced stages. Circular RNA (circRNA) and exosomes have been documented as significant contributors to the advancement of tumor cells, but the specific regulatory mechanisms between them is unclear. Therefore, our study attempts to explore the mechanism between them.

Methods: Firstly, we isolated and identified exosomes, and then validated their role in UCEC progression by experiments in vivo and in vitro. Secondly, a human competing endogenous RNA (ceRNA) array was used to identify the circRNA with the most significant differences in expression from serum of UCEC patient, and validated its role in UCEC progression by experiments in vitro. Then, we find the target gene of this circRNA by RNA sequencing, and further clarify the correlation between the 2 and their role in tumor cell progression through experiments in vitro.

Results: Serum exosomes in patients with UCEC can promote the progression of UCEC. The human ceRNA array identified that circRNA 0002577 (circ_0002577) was up-regulated and was the most significantly altered circRNA. Moreover, the up-regulated circ_0002577 in exosomes derived from UCEC patients promote proliferation and migration of UCEC. Based on RNA sequencing results, general transcription factor II-I repeat domain-containing 1 (GTF2IRD1) gene was identified as being highly correlated with circ_0002577. Additionally, a positive correlation between circ_0002577 and GTF2IRD1 was confirmed by experiments in vitro.

Conclusion: Exosomes promote UCEC progression through circ_0002577 mediated regulation of GTF2IRD1, highlighting the potential therapeutic targets in treatment for UCEC.