LINC01094 promotes gastric cancer through dual targeting of CDKN1A by directly binding RBMS2 and HDAC1.

Abstract

Background: Accumulating studies have focused on long noncoding RNAs (lncRNAs) because of their regulatory effects on multiple cancers. However, the biological functions and molecular mechanisms of lncRNAs in gastric cancer (GC) remain to be elucidated in depth.

Methods: Long intergenic nonprotein coding RNA 1094 (LINC01094), a differentially expressed lncRNA between GC tissues and adjacent normal tissues, was identified. Moreover, gain- and loss-of-function experiments in vitro and in vivo were carried out. To understand the mechanisms underlying the regulatory effects of LINC01094, we performed RNA pull-down assays, RNA immunoprecipitation assays, chromatin immunoprecipitation assays, luciferase reporter assays, etc. RESULTS: LINC01094 was markedly upregulated in GC tissues and cell lines, and LINC01094 upregulation was positively correlated with GC malignant behaviours in vitro and in vivo. Mechanistically, LINC01094 downregulated the expression of CDKN1A by interacting with RNA binding motif single stranded interacting protein 2 (RBMS2) and histone deacetylase 1 (HDAC1). Additionally, LINC01094 was confirmed to sponge miR-128-3p and participate in the LINC01094-miR-128-3p-RUNX family transcription factor 1 (RUNX1) feedback loop. Finally, Ro 5-3335, a validated RUNX1 inhibitor, was explored for anticancer drug development in GC.

Conclusions: The LINC01094-miR-128-3p-RUNX1 feedback loop downregulates CDKN1A and promotes GC cooperatively with RBMS2 and HDAC1. Furthermore, Ro 5-3335 may hold promising therapeutic potential in the treatment of GC. Hence, our study found an oncogenic lncRNA, LINC01094, which could be a promising target for cancer treatment and diagnosis.