RNA N6-methyladenosine modification in regulating cancer stem cells and tumor immune microenvironment and its implication for cancer therapy

Therapy resistance is a well-known phenomenon in cancer treatment. It can be intrinsic or acquired, accountable for frequent tumor relapse and death worldwide. The interplay between cancer cells and their neighboring environment can activate complex signaling mechanisms influencing epigenetic changes and maintain cancer cell survival leading to the malignant phenotype. Cancer stem cells (CSCs) are tumor-initiating cells (TICs) and constitute the primary source of drug resistance and tumor recurrence. Studies have shown that cancer cells exhibit dysregulated RNA N6-methyladenosine (m6A) writers, erasers, and readers levels after acquiring drug resistance. The present review provides novel insight into the role of m6A modifiers involved in CSC generation, cancer cell proliferation, and therapy resistance. m6A RNA modifications in the cross-talk between CSC and the tumor immune microenvironment (TIME) have also been highlighted. Further, we have discussed the therapeutic potential of targeting m6A machinery for cancer diagnosis and the development of new therapies for cancer treatment.

Automated summary

Therapy resistance in cancer treatment is a well-known phenomenon that leads to frequent tumor relapse and death. Cancer stem cells (CSCs) play a crucial role in drug resistance and tumor recurrence. Studies have shown dysregulated levels of RNA N6-methyladenosine (m6A) modifiers in drug-resistant cancer cells. This review explores the role of m6A modifiers in CSC generation, cancer cell proliferation, and therapy resistance, as well as their interaction with the tumor immune microenvironment (TIME). The therapeutic potential of targeting m6A machinery for cancer diagnosis and treatment is also discussed.