βKlotho Inhibits Cell Proliferation by Downregulating ELK4 and Predicts Favorable Prognosis in Prostate Cancer

Abstract

Objective Prostate cancer (PCa) ranks as the second common malignancy in males worldwide. Although conspicuous progressions in diagnosis and treatment have been achieved in the past decades, the prognosis expectation of PCa remains unsatisfied yet. To improve the prognosis prediction of PCa, more specific biomarkers are needed. In this retrospective research, we focused on βKlotho and ETS-like transcription factor 4 (ELK4), aiming to identify potential prognostic biomarkers for PCa. Methods Western blotting was used to determine the expression of βKlotho, ELK4, and PARP in C4-2B and PC3 PCa cell lines. CCK-8 assay and colony formation assay were applied to examine the roles of βKlotho and ELK4 in the proliferation of PCa cells. The expression of βKlotho and ELK4 in PCa tissue samples was determined by immunochemistry. Pearson’s χ2 test and Fisher’s exact test were performed to investigate the associations among βKlotho, ELK4 and various clinical factors. Kaplan–Meier curves and Cox regression model were established to reveal the correlation among βKlotho, ELK4 expression and the prognosis of patients. Results βKlotho overexpression down-regulated the ELK4 expression, induced apoptosis and inhibited cell proliferation in both C4-2B and PC3 cells, which were reversed by ELK4 overexpression. βKlotho expression in PCa tissue samples had negative correlation with the ELK4 expression, and higher βKlotho expression was associated with lower Gleason score, absent distant metastasis and lower prostate-specific antigen (PSA) level. On the contrast, higher ELK4 expression was correlated with distant metastasis and higher PSA level. Moreover, βKlotho and ELK4 were both recognized as independent factors for the prognosis of patients with PCa. Conclusion βKlotho inhibits proliferation of prostate cancer cells by downregulating ELK4. Both βKlotho and ELK4 expressions correlate with the prognosis of PCa, which may serve as potential biomarkers for follow-up surveillance and prognostic assessments.

Inhibiting androgen receptor splice variants with cysteine-selective irreversible covalent inhibitors to treat prostate cancer

“…S4 B ). While SP2, ELK4, and E2F are implicated in tumor growth and metastasis, CCAAT-binding transcription factors have been found to be good prognostic indicators in cancer ( 60 – 63 ). The genome browser tracks are shown in SI Appendix , Fig.…”

ELK4 Promotes Cell Cycle Progression and Stem Cell-like Characteristics in HPV-associated Cervical Cancer by Regulating the FBXO22/PTEN Axis

“…Several studies have reported that ELK4 expression is involved in the formation of a tumor. ELK4 acts as a prognostic marker, and it is highly expressed in various cancers, such as glioblastoma, 13 prostate cancer, 14 esophageal squamous cell carcinoma, 15 and breast cancer. 16 ELK4 promotes cell proliferation and its presence indicated a poor prognosis in patients.…”

“…Changlin, et al also reported that β-Klotho downregulated the expression of ELK4, inducing apoptosis and inhibition of cell proliferation in prostate cancer cells. 14 Furthermore, a persistent HPV infection may accelerate the progression to CC. For instance, CaCxSLCs exhibited highly tumorigenic abilities through selectively overexpressing the HPV oncoprotein E6 in the CC stem cells.…”