MiRNA pattern in hypoxic microenvironment of kidney cancer – role of PTEN

ABSTRACT: MicroRNAs are post-transcriptional regulators of gene expression, disturbances of their expression are the basis of many pathological states, including cancers. The miRNA pattern in the context of tumor microenvironment, explains mechanisms related to cancer progression and pro-vides a potential target of modern therapies. Here we show how tumor hypoxia modifies the miRNA pattern in renal cancer focusing on the dysregulation PTEN being a major tumor suppressor for its regulation of others key suppressors. Methods comprised the CRSPR/Cas9 mediated PTEN knockout in Renca kidney cancer cell line and global miRNA expression analysis in both in vivo and in vitro (in normoxic and hypoxic conditions). The results were validated on human cancer models with distinct PTEN status. The increase in miR210-3p in hypoxia was universal, however, the hypoxia-induced decrease in PTEN was associated with an increase in miR-221-3p, the loss of PTEN affected differently the response to hypoxia by decreasing miR-10b-3-5p and increasing miR-206-3p. In turn, Complete loss of PTEN induces miR-155-5p, miR-100-5p. Upregulation of miR342-3p in knockout PTEN occurred in the context of whole tumor microenvironment. Thus effective identification of miRNA patterns in cancers must consider the specificity of the tumor microenvi-ronment together with the mutations of key suppressors.

ORGANISM(S): Mus musculus

PROVIDER: GSE197301 | GEO | 2022/05/10

REPOSITORIES: GEO