Noncoding RNA (ncRNA)-mediated regulation of TLRs: critical regulator of inflammation in tumor microenvironment.

Toll-like receptors (TLRs) are central components of the innate immune system as they recognize molecular patterns associated with pathogens and cellular damage and initiate immune responses using MyD88- and TRIF-dependent pathways. In contrast to being very useful for immune defense, dysregulated TLR signaling may be involved in diseases, such as cancer and autoimmune conditions. In cancer, TLRs create an environment that supports tumorigenesis and growth. In addition to this, a class of multifunctional noncoding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, regulate gene expression without encoding proteins. MiRNAs regulate gene expression in a fine-tuned manner, while lncRNAs and circRNAs do so via diverse mechanisms. Notably, these ncRNAs interact, where lncRNAs and circRNAs function as competing endogenous RNAs and ceRNA, affecting miRNA activity. This interaction has a vital role in cancer pathology, in influencing that of various oncogenes and tumor suppressors in the tumor microenvironment; hence, modulation of ncRNAs could also be a great promising therapeutic approach. In this context, interplay between TLRs and ncRNAs is of paramount importance as they influence various parameters of the tumor microenvironment. TLR signaling works upon the expression of ncRNAs, while ncRNAs work back to regulate TLR signaling in return. An example of this includes miRNA targeting of components of the TLR; lncRNAs induced by TLR signaling possibly would favor tumor progression. Pharmacological interventions directed toward inhibiting these TLR pathways could be the model to halt malignancy by hampering pro-tumor inflammation and boosting immune responses against neoplasms. Hence, the review will highlight the complicated contrast of ncRNAs and TLRs within human cancer. By connecting the mechanisms, the researchers may study more about tumorigenesis and gather up new, innovative notions regarding therapeutic targeting.