A long non-coding RNA OLBC15 promotes triple-negative breast cancer progression via enhancing ZNF326 degradation

Background: The long non-coding RNAs (lncRNAs) have been involved in various processes, including cancer. However, the function of many lncRNAs is still elusive in triple-negative breast cancer (TNBC).

Methods: LncRNA profiling was used to screen for novel lncRNAs related to TNBC. OLBC15 expression was measured via qRT-PCR. In vitro migration and viability assays were conducted to determine the oncogenic role of OLBC15. Xenograft and metastatic models were performed to further investigate effects in vivo. RNA immunoprecipitation (RIP), mass spectrometry (MS), and fluorescence in situ hybridization (FISH) strategies were designed to identify the interaction between ZNF326 and OLBC15.

Results: In the current study, we have identified a novel oncogenic lncRNA termed OLBC15 via lncRNA profiling. OLBC15 is highly expressed especially in triple-negative breast cancer. OLBC15 promoted viability and migration in breast cancer cells. Moreover, OLBC15 could accelerate metastasis and xenograft tumor growth. Mechanistic study suggested that OLBC15 could bind a well-characterized tumor suppressor ZNF326 and OLBC15-ZNF326 interaction resulted in ZNF326 destabilization. OLBC15 induced proteasomal ZNF326 degradation through enhanced ubiquitination. OLBC15 and ZNF326 protein expression is also negatively correlated in clinical specimens.

Conclusions: Collectively, OLBC15 may serve as an oncogenic lncRNA to facilitate TNBC progression and a putative target for therapeutic anti-breast cancer intervention.