New RNA Regulatory Network Identified in Colorectal Cancer Progression and Immune Response

Recent research led by Prof. Gu Hongcang and Zhang Fan at the Hefei Institutes of Physical Science of the Chinese Academy of Sciences has uncovered a crucial RNA-driven regulatory network influencing colorectal cancer (CRC) development and immune system interaction. Through comprehensive multi-omics analysis—integrating transcriptomic, proteomic, and metabolomic data—scientists identified key molecular alterations distinguishing CRC tissues from normal counterparts, including 1,394 differentially expressed long non-coding RNAs (lncRNAs), 2,788 mRNAs, 548 proteins, and 91 metabolites.

Among these, a particular lncRNA named lncRNA 60967.1 stood out as a central regulator. It was significantly downregulated in CRC cell lines and patient samples. Functional studies demonstrated that restoring lncRNA 60967.1 reactivates the tumor suppressor gene PLCD4 and increases all-trans retinoic acid (ATRA) levels, which in turn promotes apoptosis through interferon gamma pathways. This enhancement of immune responses partially mitigates the resistance of CRC cells to immune attack.

In vivo experiments in mouse models showed that overexpression of lncRNA 60967.1 boosted immune cell infiltration into tumors and significantly inhibited tumor growth, especially when combined with anti-PD-1 immunotherapy. These findings suggest that lncRNA 60967.1 influences both tumor progression and immune response mechanisms, presenting a promising therapeutic target.

The research, published in Molecular Cancer, highlights the importance of the newly identified lncRNA 60967.1–PLCD4–ATRA axis. Targeting this pathway could help overcome resistance in CRC treatments and improve immunotherapy efficacy. This discovery advances our understanding of CRC's molecular complexity and opens new avenues for precision medicine strategies in combating this disease.

Source: https://medicalxpress.com/news/2025-07-uncovers-key-rna-driven-network.html