Cross-Kingdom Gene regulation via miRNAs of Hypericum perforatum (St. John's wort) flower dietetically absorbed: An in silico approach to define potential biomarkers for prostate cancer.

Prostate cancer (PCa) is the most frequent type of cancer in men. Hypericum perforatum (H. Perforatum) extract (HPE) administration provides remarkable decrease of PCa development. H. perforatum contains 7 conserved miRNAs (Hyp-miR-156a, Hyp-miR-156b, Hyp-miR-166, Hyp-miR-390, Hyp-miR-394, Hyp-miR-396 and Hyp-miR-414) with different targets. In this study, we aimed to investigate cross-kingdom gene regulation via miRNAs of H. perforatum flower dietetically absorbed in manner of an in silico approach to define potential biomarkers for PCa. psRNATarget database was used to find human genes targeted by 7 pre-defined H. perforatum miRNAs. We defined the mostly affected gene families from these miRNAs as ZNF, TMEM, SLC and FAM gene families. GeneMANIA database was used to define the most affected genes (TMEM41B and SLC4A7) from these 7 miRNAs. cBioPortal database was used to define alteration frequencies of TMEM41B and SLC4A7 on different types of PCa and to measure the mutual interaction potency and significance of co-occurence in PCa. This analysis showed that neuroendocrine prostate cancer (NEPC) had the highest total mutation frequency (22%) of TMEM41B and SLC4A7 genes. Also, TMEM41B and SLC4A7 genes had an average 2.1% pathway change potential among all different types of PCa. Moreover, TMEM41B and SLC4A7 gene pair was found significantly co-occurrent in PCa (p < 0.001). Finally, via GEPIA database, we used Spearman correlation analysis to measure the correlation degree of TMEM41B and SLC4A7 genes in PCa and found their significant correlation with PCa (p = 1.2 × 10^-12, R = 0.28). All in all, it was proved in silico and supported with previously known clinical data that SLC4A7 and TMEM41B potentially have a significant and critical tumor suppressive role for PCa, and show this effect combinatorily working together. This is the first study correlating SLC4A7 and TMEM41B with PCa significantly.