UCA1 executes an oncogenic role in pancreatic cancer by regulating miR-582-5p/BRCC3

Xiaole Hu; Jiahao Wu; Jianwei Xu

doi:10.3389/fonc.2023.1133200

UCA1 executes an oncogenic role in pancreatic cancer by regulating miR-582-5p/BRCC3

Front Oncol. 2023 Jul 25:13:1133200. doi: 10.3389/fonc.2023.1133200. eCollection 2023.

Authors

Xiaole Hu¹, Jiahao Wu², Jianwei Xu²

Affiliations

¹ Department of First Operating Room, Qilu Hospital of Shandong University, Jinan, China.
² Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Shandong University, Jinan, China.

Abstract

Background: As a fatal disease, the mechanism of pancreatic cancer is unclear. Urothelial carcinoma antigen 1(UCA1), a long noncoding RNA (lncRNA) that was first reported in bladder cancer, acts as an oncogene. However, the regulatory role and mechanism of UCA1 in pancreatic cancer remain unknown. This study aims to investigate the expression level and prognostic value of UCA1 in pancreatic cancer tissues, the effects and mechanism of UCA1 in regulating cell proliferation, apoptosis and metastasis.

Methods: UCA1 expression levels in tissues were detected by in situ hybridization (ISH) and the prognostic value was evaluated by univariate and multivariate survival analysis. For in vitro experiments, proliferation was evaluated by a cell count kit assay, Edu experiments, and a clone formation assay. Apoptosis was evaluated by fluorescence-activated cell sorting flow-cytometry. Cell migration and invasion capacities were detected by wound healing and transwell assays. Western blots were performed to detect apoptotic associated molecules and epithelial-mesenchymal transition (EMT) markers. For the in vivo experiment, subcutaneous transplantation models of pancreatic cancer in nude mice were established to observe the tumor growth. The regulatory mechanism of UCA1 was explored by proteomics, bioinformatic analysis, luciferase reporter assays, and rescue experiments.

Results: ISH staining revealed that UCA1 levels between cancer tissues (n=94) and tumor-adjacent tissues (n=73) did not show significant differences. Survival analysis indicated that high expression of UCA1 was an unfavorable prognosis factor for pancreatic cancer. Downregulation of UCA1 by siRNA significantly inhibited cell proliferation, decreased the capacities of cell migration and invasion, induced cell apoptosis, and inhibited EMT. Furthermore, we demonstrated that UCA1 positively regulated the expression of BRCC3 by inhibiting miR-582-5p. Rescue experiments indicated that either inhibiting the expression of miR-582-5p or enhancing expression of BRCC3 could partly attenuate the antitumor effects of downregulation of UCA1.

Conclusion: UCA1 acted as an oncogene in pancreatic cancer by partly regulating miR-582-5p/BRCC3, which could be a new therapeutic target for pancreatic cancer.

Keywords: ceRNA; lncRNA; miRNA; pancreatic cancer; prognosis.

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (81502051), the Shandong Provincial Natural Science Foundation, China (ZR2020MH256), the Postdoctoral Research Foundation of China (2018M632681), Special Support for Post-doc Creative Funding in Shandong Province (201902009), Medical Health Science and Technology Project of Shandong Provincial Health Commission (2019WS386), Basic Cancer Research Program Supported by Bethune Charitable Foundation (BCF-NH-ZL-20201119-009).