Enzalutamide-resistant related lncRNA NONHSAT210528 promotes the proliferation and invasion of prostate cancer

Chen Ye; Yuan-Gui Chen; Sheng-Fei Qin; Shou-Yan Tang; Song Li; Min-Feng Shi; Tie Zhou

doi:10.21037/tau-22-99

Enzalutamide-resistant related lncRNA NONHSAT210528 promotes the proliferation and invasion of prostate cancer

Transl Androl Urol. 2022 May;11(5):643-658. doi: 10.21037/tau-22-99.

Authors

Chen Ye^#¹, Yuan-Gui Chen^#¹, Sheng-Fei Qin¹, Shou-Yan Tang¹, Song Li¹, Min-Feng Shi², Tie Zhou³

Affiliations

¹ Department of Urology, Shanghai Changhai Hospital, Shanghai, China.
² Reproduction Center, Shanghai Changhai Hospital, Shanghai, China.
³ Department of Urology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

^# Contributed equally.

Abstract

Background: As a new-generation androgen-receptor antagonist, enzalutamide is a first-choice drug for advanced prostate cancer (PCa) patients. However, secondary resistance to enzalutamide poses a new challenge in the treatment of cancer. Long non-coding RNA (lncRNA) regulates cell function through many levels and mechanisms, and also plays an important role in the biological behaviors of tumors.

Methods: LncRNA microarrays were used to detect enzalutamide-resistant related lncRNA in Enzalutamide-resistant C4-2 (C4-2 ENZ-R) cells and corresponding parent cells. Cell Counting Kit 8, flow cytometry, and transwell assays were used to test the effect of lncRNA NONHSAT210528 on the function of PCa cells. RNA pulls down and the luciferase report gene was used to detect the competitive endogenous RNA (ceRNA) mechanism. The culture supernatant of C4-2 and C4-2b cells was transferred to the lower chamber for transwell assay of human umbilical endothelial cells (HUVECs).

Results: The lncRNA microarray analysis showed that there were significant differences in the expression of many lncRNAs between the C4-2 ENZ-R and C4-2 cells. The real-time polymerase chain reaction (PCR) detection showed that the expression of lncRNA NONHSAT210528 was significantly higher in the C4-2 ENZ-R cells than the C4-2 cells. The Transwell assays showed that lncRNA NONHSAT210528 overexpression increased the invasion of the C4-2 and C4-2b cells. The cell-wound scratch and the transwell assays showed that the culture supernatant of C4-2 and C4-2b cells with overexpressed lncRNA NONHSAT210528 promoted the migration and invasion of HUVECs. Furthermore, lncRNA NONHSAT210528 regulated the expression of YOD1 dependent on miR-21.

Conclusions: Enzalutamide-resistant related lncRNA NONHSAT210528 appears to promote the proliferation and invasion of PCa cells by functioning as a ceRNA and regulating the miR-21-5p/YOD1 signal pathway.

Keywords: Enzalutamide; YOD1; long non-coding RNA (lncRNA); miRNA; prostate cancer (PCa).