Molecular Mechanism of hsa-circKLK3-25 in Regulating Prostate Cancer Progression via the JNK/ERK Signal Transduction Pathway

Background: PCa (representing prostate cancer) ranks among the most prevalent malignancies in males. This disease begins insidiously. Most patients have reached an advanced stage when being diagnosed for the first time. Moreover, this condition is prone to distant metastasis, leading to an unfavorable prognosis. Therefore, the paramount thing is to find the biomarkers underlying this disease to facilitate the early diagnosis of PCa. Methodology: A high-throughput sequencing method was taken to identify the circular RNA, hsa-circKLK3-25, in PCa tissues. Next, the expression and stability of hsa-circKLK3-25 were assessed by qRT-PCR and Actinomycin D testing. Followed by, PCa cells were transfected with hsa-circKLK3-25 or sh-hsa-circKLK3-25 and tested through CCK-8, Edu, scratch healing and transwell experiments to make clear the influences of heightening or silencing hsa-circKLK3-25 on the aggressive evolution of PCa cells. Afterward, western blot experiments were carried out to determine the expressions of proteins associated with the JNK/ERK signal transduction pathway and judge whether hsa-circKLK3-25 effected by virtue of the JNK/ERK pathway. Finally, subcutaneous xenograft tumor models were formed in nuke mice to uncover the interference of hsa-circKLK3-25 with the evolution of PCa cells in vivo. Results: The high-throughput sequencing results confirmed the presence of hsa-circKLK3-25 in PCa tissues. In PCa cells, hsa-circKLK3-25 was at a notably and stably heightened level. Excessive hsa-circKLK3-25 propelled PCa cells to multiply, penetrate, and migrate; conversely, silenced hsa-circKLK3-25 impaired the aggressive evolution of such cells. Overexpression of hsa-circKLK3-25 led to an upregulation in the expressions of proteins associated with the JNK/ERK pathway, while silencing hsa-circKLK3-25 lead to the opposite trend. The cancer-promoting effect of excessive hsa-circKLK3-25 was retarded following the administration of the inhibitors for this pathway. Besides, in vivo experiments demonstrated that silencing hsa-circKLK3-25 leveled down the expressions of proteins associated with the said pathway and could suppress the expansion of tumors. Conclusion: hsa-circKLK3-25 is at a notably over-high level in PCa cells and promotes the aggressive evolution of PCa in vitro/vivo through the JNK/ERK signal transduction pathway.