Extracellular Vesicle-Mediated Transfer of LncRNA IGFL2-AS1 Confers Sunitinib Resistance in Renal Cell Carcinoma.

ABSTRACT: Sunitinib resistance remains a serious challenge to the treatment of advanced and metastatic renal cell carcinoma (RCC), yet the mechanisms underlying this resistance are not fully understood. Here, we report that the long noncoding RNA IGFL2-AS1 is a driver of therapy resistance in RCC. IGFL2-AS1 was highly upregulated in sunitinib-resistant RCC cells and was associated with poor prognosis in patients with clear cell RCC (ccRCC) who received sunitinib therapy. IGFL2-AS1 enhanced TP53INP2 expression by competitively binding to hnRNPC, a multifunctional RNA-binding protein that posttranscriptionally suppresses TP53INP2 expression through alternative splicing. Upregulated TP53INP2 enhanced autophagy and ultimately led to sunitinib resistance. Meanwhile, IGFL2-AS1 was packaged into extracellu

SUBMITTER: Pan Y 

PROVIDER: S-EPMC9811158 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature