Abstract

Epidermal growth factor receptor (EGFR) stands out to being a key player in promoting the progression to an invasive, metastatic state in prostate cancer (PCa). However, the precise molecular mechanisms regulating EGFR in relation to early detection and recurrence in advanced stages are still unclear. Thus, in the current study, we investigated the protein expression of EGFR in PCa patients and mouse tissue by immunohistochemistry and western blot technique using PCa cell lines. Relative expression of EGFR and its associated microRNAs (miRNAs) and circular RNAs (circRNAs) were investigated in PCa cell lines DU145 and LNCaP by real-time quantitative PCR and data were compared using a non-parametric t-test. In our study, we identified three up-regulated (hsa-miR-1199, hsa-miR-7110, and hsa-miR-6778) and four downregulated (miR-936, miR-1275/4665-5p, miR-423-5p, and miR-493-5p) EGFR binding miRNAs in metastatic PCa. Furthermore, circRNAs, of EGFR and its associated phospholipid-binding protein, Annexin A2, such as hsa_circ_0035565, hsa_circ_0080228, hsa_circ_0080221, and hsa_circ_0080222 were upregulated in metastatic PCa cell lines, while their targets miR-936, miR-1275/4665-5p, miR-423-5p, and miR-493-5p were downregulated. EGFR is essential in driving the advancement of PCa towards an invasive and metastasis. miRNAs associated with EGFR, with their corresponding circRNAs, might play a significant role in regulating the differential expression of EGFR in hormone-dependent and hormone-independent metastatic PCa.

Key words: EGFR, Biomarker, circular RNA, micro-RNA, Prostate Cancer