RNA Regulator of Lipogenesis (RROL)

RNA Regulator of Lipogenesis (RROL), also known as lnc-17-92, is a long non-coding RNA (lncRNA) derived from the MIR17HG gene locus (Morelli et al., 2023). It plays a critical role in the metabolic reprogramming of cancer cells, particularly in multiple myeloma, by acting as a chromatin scaffold that facilitates the assembly of a transcriptional complex consisting of c-MYC and WDR82 (Morelli et al., 2023). This complex specifically targets and activates the promoter of the ACC1 (ACACA) gene, the rate-limiting enzyme in de novo lipogenesis, leading to increased fatty acid synthesis (Morelli et al., 2023; AACR, 2023). This metabolic adaptation is essential for the proliferation and survival of malignant plasma cells, and high expression of RROL is associated with disease progression and poor clinical outcomes (Morelli et al., 2023). Therapeutic strategies focusing on RROL utilize antisense oligonucleotides (ASOs) to deplete the lncRNA, effectively disrupting the oncogenic lipogenic axis and inhibiting tumor growth in preclinical models (Morelli et al., 2023).

Other names

lnc-17-92MIR17HG-RROLMIR17HGLong non-coding RNA regulator of lipogenesisMIR17HG-derived lncRNA

RNA Regulator of Lipogenesis (RROL) acts as a chromatin scaffold that facilitates the functional interaction between the transcription factor c-MYC and the WD repeat-containing protein 82 (WDR82) (Morelli et al., 2023). This assembly promotes the recruitment of the complex to the promoter of the Acetyl-CoA Carboxylase 1 (ACC1/ACACA) gene, leading to its transcriptional and epigenetic activation (Morelli et al., 2023). Increased ACC1 expression drives de novo lipogenesis, providing the necessary fatty acids for the rapid proliferation and survival of multiple myeloma cells (Morelli et al., 2023). Therapeutic targeting involves using antisense oligonucleotides to degrade RROL, thereby disrupting the lipogenic pathway and inducing anti-tumor effects (Morelli et al., 2023).