Abstract
<title>Abstract</title> <p>Background Clear cell renal cell carcinoma (ccRCC) exhibits a high metabolic plasticity and a poor prognosis. However, the mechanisms of long non-coding RNA (lncRNA) RP11-893F2.9 affect the prognosis of ccRCC through metabolic pathways remains unclear. Methods The role and mechanism of RP11-893F2.9 in ccRCC were investigated by RNA pull-down, actinomycin D assay, western blot, transwell cell migration and invasion, and colony formation assays. Results RP11-893F2.9 promoted the transcription of TMEM92 through HNRNPK, thereby facilitating the growth, migration and invasion of ccRCC cells. RNA-seq revealed enrichment of glutamine metabolism, among which glutamine synthase (GLUL) induction is the most significant. Mechanistically, TMEM92 interacted with Yes-associated protein 1 (YAP1) on the nuclear membrane, facilitating its nuclear translocation and upregulating GLUL. YAP1 knockdown can abolish GLUL induction by RP11-893F2.9. Conclusions RP11-893F2.9, as an AR-activated oncogenic lncRNA, promoted the initiation of ccRCC through the HNRNPK/TMEM92/YAP1/GLUL axis, reprogramed glutamine-fatty acid metabolism and drived the progression of ccRCC.</p>