Hypoxia-Related Tumor Acidosis Affects MicroRNA Expression Pattern in Prostate and Breast Tumor Cells.

MicroRNAs (miRNAs) are small non-coding RNA sequences which are able to modulate the expression of many functional proteins. The expression level of miRNAs can be modulated by parameters of the tumor microenvironment like hypoxia, nutrient deprivation or oxidative stress. Since miRNAs can act either as oncogenes or tumor suppressors, this may affect malignant progression or therapy resistance. In the present study it was analyzed whether extracellular acidosis can impact on miRNA expression. Therefore, tumor cells (R3327-AT-1 prostate and Walker-256 mammary carcinoma cells) were incubated at pH 6.6 (acidosis) or pH 7.4 (control) for 24 h and changes in miRNA expression were analyzed by PCR array for 84 cancer-associated miRNAs and Next-Generation Sequencing (NGS) with a panel of 765 miRNAs.In the cancer-related PCR array an acidosis-induced reduction of 5 miRNAs in AT-1 and 6 miRNAs in Walker-256 cells was seen. The miR-203a was consensually down-regulated in both cell lines. Using NGS, 19 miRNAs were found to be upregulated and 14 miRNAS were downregulated in AT-1 prostate cancer cells. In Walker-256 cells the expression of 21 miRNAs was increased and decreased for 17 miRNAs. Eleven miRNAs were regulated by acidosis in both tumor cell lines in the same direction.Acidosis induced changes in the miRNA expression of prostate and breast carcinoma cells. However, miRNA profiles differed strongly between the tumor cell lines (and between the experimental methods used), indicating that cells can react individually to microenvironmental stress. However, some miRNAs were consensually regulated in both cell lines and thus might represent a general cellular response to an extracellular acidosis.