An epigenetic perspective on tumorigenesis: Loss of cell identity, enhancer switching, and NamiRNA network. (August 2022)

• Record Type: Journal Article
• Authors: Liang, Ying; Xu, Peng; Zou, Qingping; Luo, Huaibing; Yu, Wenqiang
• Is Part Of: Seminars in cancer biology. Volume 83(2022)
• Page Start: 596
• Page End: 604
• Publication Date: 2022-08
• Subjects: AFP alpha-fetoprotein -- ATRA All-trans retinoic acid -- APL acute promyelocytic leukemia -- CML chronic myeloid leukemia -- CR complete remission -- Ctbp2 C-terminal binding protein 2 -- eRNA enhancer RNA -- ESC embryonic stem cell -- GBM glioblastoma -- HPC hematopoietic progenitor cells -- iPSC induced pluripotent stem cells -- LEF1 lymphoid enhancer-binding factor 1 -- LOCI loss of cell identity -- Isl1-Lhx3 Islet-1-LIM homeobox 3 -- NamiRNA nuclear activating miRNA -- NDRs nucleosome-depleted regions -- NOMe-seq nucleosome occupancy and methylome sequencing -- NSCs neural stem cells -- NSRs Nucleosome Secured Regions -- NuRD Nucleosome Remodeling and Deacetylation -- SNP single-nucleotide polymorphisms -- SVZ subventricular zone -- T-ALL T-cell acute lymphoblastic leukemia -- TALEN transcription activator-like effector nuclease; Loss of cell identity (LOCI) -- NamiRNA–enhancer–gene activation network -- Enhancer -- Tumor initiation; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2018.09.004
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: Various tumorigenic theories have been proposed in the past century, which contribute to the prevention and treatment of cancer clinically. However, the underlying mechanisms of the initiation of cancer, drug resistance, neoplasm relapse, and metastasis are still challenging to be panoramically addressed. Based on the abundant evidence provided by others and us, we postulate that Tumor Initiated by Loss of Cell Identity (LOCI), which is an inevitable initiating event of tumorigenesis. As a result, normal cells are transformed into the cancerous cell. In this process, epigenetic regulatory program, especially NamiRNA (Nuclear activating miRNA)–enhancer–gene activation network, is vital for the cell identity. The disorganization of NamiRNA–enhancer–gene activation network is a causal predisposition to the cell identity loss, and the altered cell identity is stabilized by genetic variations of the NamiRNA–enhancer–gene activation network. Furthermore, the additional genetic or epigenetic abnormities confer those cells to carcinogenic characteristics, such as growth advantage over normal cells, and finally yield cancer. In this review, we literally explain our tumor imitation hypothesis based on the corresponding evidence, which will not only help to refresh our understanding of tumorigenesis but also bring benefits to developing "cell identity reversing" based therapies.