Background/Objectives: The oral–gut–lung axis represents a dynamic system where exosomes carrying mRNAs and non-coding RNAs might help to regulate microbiota and human cell crosstalk to establish transcriptional regulatory networks controlling cellular biological processes and signaling pathways. Methods: We conducted a comprehensive transcriptomic analysis to characterize the molecular cargo of extracellular exosomes in the context of gut and lung cancer. Results: By analyzing gut and lung exosomes cargo with our previous transcriptomic studies from tumoral and inflammatory tissues, we found that exosomes can transport key RNAs that codify specific receptors that facilitate pathogenic interaction with microorganisms and RNAs that are part of interacting gene and transcriptional regulatory networks that control the function of differentially expresses genes, all involved in biological processes like cell cycle, plasticity and growth regulation, invasion, metastasis, microenvironmental remodeling, epigenetic, and microbial and immunological modulation, during the unlocking of phenotypic plasticity for the acquisition of the hallmarks of cancer in the oral–gut–lung axis. Conclusions: Exosomal RNA regulation of transcriptional networks represents a pivotal axis in the interplay between inflammation and cancer, offering opportunities for innovative diagnostic and therapeutic approaches.

Lung-cancer cell-cycle progression is shaped by interacting checkpoint, transcriptional, chromatin, and non-coding RNA regulatory layers rather than by isolated molecular alterations. This integrative review uses SMARCB1, NOC2L, CDCA4, and CHEK1 as four complementary anchor regulators representing SWI/SNF-dependent chromatin remodeling, inhibition of histone acetyltransferase activity, E2F-linked transcriptional modulation, and checkpoint signaling, respectively. We critically map their literature-supported relationships across G1, S, G2, and M and integrate DNA and histone methylation, acetylation, chromatin remodeling, phosphorylation, ubiquitination, hydroxylation, and non-coding RNA regulation. Importantly, lung-cancer-specific evidence is distinguished from evidence extrapolated from other tumor models, and experimentally established mechanisms are separated from contextual or hypothesis-generating phase assignments. The strongest lung-specific evidence concerns CHEK1 dependence, replication stress, and chromatin-state plasticity, whereas several proposed phase-specific functions of NOC2L, CDCA4, and SMARCB1 remain incompletely validated in lung cancer. Recent 2026 studies further emphasize subtype-specific CHEK1 biology, therapy-associated chromatin reprogramming, and long non-coding RNA control. This framework identifies testable regulatory hypotheses while avoiding interpretation of network association as direct causality.