The lncRNA011760/miR-novel-91/<em>NIPA2 </em>ceRNA Network Regulates Salinity Stress Response in Sea Cucumber (<em>Apostichopus japonicus</em>)

Abstract Low-salinity stress poses a critical constraint on the commercial aquaculture and survival of the sea cucumber (Apostichopus japonicus). This study investigated the regulatory network involving lncRNA011760, miR-novel-91, and their target gene NIPA2 in response to salinity fluctuations. Using integrated in vivo and in vitro functional assays, we demonstrate that lncRNA011760 acts as a competitive endogenous RNA (ceRNA) to sponge miR-novel-91, thereby alleviating the post-transcriptional repression of NIPA2. Based on these molecular dynamics, we propose a novel inhibition-adaptation-survival three-stage model. Initially (0–3h), acute NIPA2 upregulation enhances Mg²⁺ transport efficiency to mitigate osmotic shock. During the mid-stage (3–24 h), miR-novel-91-mediated NIPA2 suppression creates a transient biosynthetic window, facilitating a shift from passive tolerance to active metabolic adaptation. Ultimately (24–48 h), lncRNA-driven NIPA2 restoration sustains Mg²⁺ homeostasis, allowing the organism to enter a low-metabolism survival mode. These stage-specific shifts reflect the inherent physiological strategies of sea cucumbers as osmoconformers. Our findings elucidate the complex epigenetic orchestration of osmotic stress tolerance and highlight the lncRNA011760/miR-novel-91/NIPA2 axis as a promising molecular target for the marker-assisted breeding of salt-tolerant strains.