Interplay within tumor microenvironment orchestrates neoplastic RNA metabolism and transcriptome diversity

Area of Science:

• Molecular Oncology
• Cancer Biology
• RNA Biology

Background:

• Tumor heterogeneity and the tumor microenvironment (TME) are critical drivers of cancer progression.
• The interplay between cancer cells and the TME influences immune evasion, angiogenesis, metastasis, and therapeutic resistance.
• Transcriptomic alterations, including mRNA and noncoding RNA modifications, are central to these processes.

Purpose of the Study:

• To review the multifaceted influence of TME components on cancer-associated RNA metabolism.
• To highlight transcriptomic adaptations to the physicochemical conditions of the TME.
• To analyze therapeutic strategies targeting TME-mediated RNA regulation.

Main Methods:

• Comprehensive literature review of studies investigating TME-cancer cell interactions.
• Categorization of TME components and their impact on RNA synthesis, modification, stability, and processing.
• Analysis of transcriptomic responses to TME-associated stressors like hypoxia and acidosis.

Main Results:

• TME components profoundly shape cancer cell transcriptomes, affecting RNA metabolism.
• Physicochemical TME factors induce specific transcriptomic adaptations.
• RNA metabolism is a key mechanism underlying immune tolerance, angiogenesis, metastasis, and therapy resistance.

Conclusions:

• Targeting TME-driven RNA metabolism offers promising therapeutic avenues.
• Modulating RNA processing and stability within the TME can impede cancer progression.
• Further research into TME-specific RNA regulation is crucial for advancing cancer therapy.