Efficient tumorigenesis by mutation-induced failure to terminate microRNA-mediated adaptive hyperplasia.

摘要: Seven current contending cancer theories consider different sets of critical events as sufficient for tumorigenesis. These theories, most recently the microRNA dysregulation (MRD) theory, have overlapping attributes and extensive empirical support, but also some discrepancies, do not address both benign malignant By definition, efficient tumorigenic pathways will dominate under conditions that selectively activate those pathways. The MRD theory provides a mechanistic basis to combine elements into new hypothesis that: (i) tumors arise efficiently stress induces sustains either protective or regenerative states adaptive hyperplasia (AH) normally are epigenetically maintained unless terminated; (ii) if dysregulated by somatic mutation prevents normal termination, these two AH can generate tumors, respectively. This hypothesis, multistage predicts key participating AH-stem-cell populations expand markedly when triggered stress, particularly chronic metabolic oxidative mechanical irritation, toxic exposure, wounding, inflammation, and/or infection. expression patterns in vs. tumor tissue correlate best with governing tissue, inmutagen-exposed stem cells happen be in, incidentally later become recruited into, an state.