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RTN3 (Reticulon 3) as a Novel Prostate Cancer-Specific Biomarker derived from Exosome

Ye-Eun Kim, Anh-Thu Nguyen, Jin woo Min, Mi Jung Kim, Ki-Young Kim, Hee cheol Kang

Objective: Prostate cancer accounts for a large proportion of male cancer deaths worldwide.

Commonly used prostate-specific antigens (PSA) lead to over diagnosis, so novel prostate cancer diagnostic markers are needed. Several substances derived from exosomes affect the progression of cancer. Therefore, it is possible to predict the cancer progression through exosome derived markers.

Design: In order to find a candidate protein that can be used as a biomarker among the exosomal protein coding 7145 genes, screening was performed using qRT-PCR. The genes selected through screening were subjected to western blot to confirm protein expression in cells and protein expression in cancer cell derived exosomes. Afterwards, the function of the corresponding exosomal protein was confirmed through Invasion Assay.

Result: As a result of screening of the expression level of RNAs in various cancer cell lines, RTN3 showed a high expression level in the prostate cancer cell lines but not in the normal prostate cell line, RWPE-1. RTN3 was also highly expressed in prostate cancer exosomes except for the normal cell line.

To verify the function of exosomal RTN3, a cell line (Malme-3M) with low RTN3 expression was treated with exosomes extracted with high RTN3 expression and showed increased metastasis.

Conclusion: RTN3 can be used as a diagnostic marker for prostate cancer because of the high expression level of RTN3 in prostate cancer derived exosomes compared with normal prostate cell derived exosome. Exosomal RTN3 is also important for cancer metastasis.