Long Non-Coding RNA PCED1B-AS1 Promotes the Progression of Clear Cell Renal Cell Carcinoma Through miR-484/ZEB1 Axis

Jianhua Qin; Tingting Zhu; Weihua Wu; Huan Chen; Yi He

doi:10.2147/OTT.S270149

Long Non-Coding RNA PCED1B-AS1 Promotes the Progression of Clear Cell Renal Cell Carcinoma Through miR-484/ZEB1 Axis

Onco Targets Ther. 2021 Jan 13:14:393-402. doi: 10.2147/OTT.S270149. eCollection 2021.

Authors

Jianhua Qin^{1

2}, Tingting Zhu^{1

2}, Weihua Wu^{1

2}, Huan Chen³, Yi He⁴

Affiliations

¹ Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, People's Republic of China.
² Sichuan Clinical Research Center for Nephropathy, Luzhou 646000, Sichuan, People's Republic of China.
³ Department of Pathogen Biology, Basic Medical College, Southwest Medical University, Luzhou 646000, Sichuan, People's Republic of China.
⁴ Department of Urology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, People's Republic of China.

Abstract

Background: Long non-coding RNA (lncRNA) has been recognized as the new regulator and biomarker for cancers. However, in clear cell renal cell carcinoma (ccRCC), the functions of lncRNAs are not well characterized. This research aimed to probe the function of lncRNA PCED1B-AS1 in the progression of ccRCC.

Materials and methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression levels of PCED1B-AS1, microRNA-484 (miR-484), and zinc finger E-box binding homeobox 1 (ZEB1) in 40 pairs of human ccRCC tissues and corresponding adjacent kidney tissue samples. Chi-square test was employed to evaluate the association between PCED1B-AS1 expression level and clinicopathological characteristics. The effects of PCED1B-AS1, miR-484 and ZEB1 on the cell proliferation, migration and epithelial-mesenchymal transition (EMT) process of ccRCC cells were studied by CCK-8 assay, EdU cell proliferation assay, wound healing test and Western blotting. The regulatory relationships among PCED1B-AS1, miR-484, ZEB1 were examined by luciferase reporter gene assay and RNA immunoprecipitation assay.

Results: PCED1B-AS1 was remarkably up-regulated in ccRCC tissues and cell lines. High expression of PCED1B-AS1 was associated with poor prognosis of the patients. Loss-of-function experiments showed that PCED1B-AS1 could regulate the proliferation, migration and EMT of ccRCC cells. PCED1B-AS1 sponged miR-484 to suppress its expression, and miR-484 targeted the 3'-UTR of ZEB1 to repress the expression of ZEB1. MiR-484 counteracted the functions of PCED1B-AS1 in promoting the proliferation, migration and EMT of ccRCC cells, and PCED1B-AS1 promotes the expression of ZEB1 via repressing miR-484.

Conclusion: PCED1B-AS1/miR-484/ZEB1 axis is involved in regulating the progression of ccRCC.

Keywords: PCED1B-AS1; ZEB1; ccRCC; miR-484.

Grants and funding

This work is supported by the National Natural Science Foundation of China (No. 81800670) and Foundation of Luzhou-Southwest Medical University (No. 2017lzxnyd-j32).