Long Noncoding RNA UCA1 Facilitates Endometrial Cancer Development by Regulating KLF5 and RXFP1 Gene Expressions.

Abstract

Objective: Long noncoding RNA urothelial carcinoma associated 1 (UCA1) was found to facilitate endometrial cancer cell metastasis, and high UCA1 expression predicted endometrial cancer development and patients' worsened outcomes. This research aimed to investigate the cancer promoting role and mechanism of UCA1 in endometrial cancer. Materials and Methods: Around 64 endometrioid adenocarcinoma patients' tissue specimens were analyzed by qRT-PCR. Primary endometrial cancer cell culture was established in vitro. UCA1 overexpression or knockdown was executed by adenoviral transduction. Cell proliferation, apoptosis, colony formation, transwell invasion, and epithelia-to-mesenchymal transition of primary endometrial cancer cells were assessed. Interactions among UCA1, microRNAs (miRNAs), and mRNAs were investigated by luciferase reporter assay and argonaute 2 (AGO2)-RNA immunoprecipitation. Nude mouse xenograft assay was used to explore the role of UCA1 in endometrial cancer in vivo. Results: UCA1 was significantly upregulated in endometrial cancer tissues compared to normal tissues. High expression of UCA1 associated with endometrial cancer progression and patients' decreased survival. Overexpressing UCA1 significantly increased the malignancy of primary endometrial cancer cells in vitro, while UCA1 knockdown showed opposite effect. Kruppel-like factor 5 (KLF5) and relaxin like family peptide receptor 1 (RXFP1) were found as two UCA1 co-expressing genes in endometrial cancer. UCA1 increased the malignancy of endometrial cells partially through KLF5, and it increased the relaxin 2-induced endometrial cancer cell metastasis through RXFP1. UCA1 reduced the si-RNA-induced silencing of KLF5 and RXFP1 genes in endometrial cancer cells. MiR-143-3p and miR-1-3p were found to interact with both UCA1 and KLF5 mRNA. In addition, knockdown of UCA1 suppressed tumor growth in endometrial cancer in vivo. Conclusion: UCA1 might facilitate endometrial cancer development by upregulating KLF5 and RXFP1 gene expression by sponging miR-143-3p and miR-1-3p.