Nuclear speckles regulate functional programs in cancer.

ABSTRACT: Nuclear speckles are dynamic nuclear bodies characterized by high concentrations of factors involved in RNA production. Although the contents of speckles suggest multifaceted roles in gene regulation, their biological functions are unclear. Here we investigate speckle variation in human cancer, finding two main signatures. One speckle signature was similar to healthy adjacent tissues, whereas the other was dissimilar, and considered an aberrant cancer speckle state. Aberrant speckles show altered positioning within the nucleus, higher levels of the TREX RNA export complex and correlate with poorer patient outcomes in clear cell renal cell carcinoma (ccRCC), a cancer typified by hyperactivation of the HIF-2α transcription factor. We demonstrate that HIF-2α promotes physical association of c

SUBMITTER: Alexander KA 

PROVIDER: S-EPMC12039181 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature