Acidosis-driven aberrations of microRNAs in endometrial cancer in vitro

Purpose: MicroRNAs have been identified as crucial regulators of carcinogenic pathways. Micro environmental alterations such as hypoxia and acidosis frequently accompany tumor progression and metastasis. Thereto expression profiles of 24 different microRNAs, exhibiting oncogenic as well as tumor suppressor functions, were investigated under the influence of these two exogenic stimuli in endometrial cancer (EC) in vitro.

Material and methods: Quantitative analyses of 24 specific microRNA specimen were performed by RNA isolation and subsequent realtime PCR from three established EC cell types. Therefore, relative quantification of the different microRNAs resulted from ΔC_t method, normalized against medium expression values of the housekeeping miRNAs RNU48 and microRNA16 under control versus hypoxic or acidic conditions.

Results: In two cell lines, derived from EC type 1, the exogenic stimulus acidosis triggered a uniform significant down-regulatory effect on the expression levels of ten microRNA phenotypes. Whereas in the third cell line, derived from EC type 2, acidosis did not affect the expression pattern significantly. Hypoxia caused no marked alterations in the expression pattern of the different microRNA types in all three EC cell lines tested.

Conclusion: Microenvironmental alterations such as acidosis lead to down-regulation of ten microRNAs in two EC type 1 cell lines, known as estrogen receptor positive. However, the molecular background of signaling pathways that undergo acidosis-dependent alterations and its concomitant effects on tumor biology still need to be investigated in more detail. Furthermore, the potential biomarker function of microRNA expression pattern in EC diagnosis (subtyping) is a future subject of this translational approach.