Biology Mechanisms Research Articles

The Double Helical Structure of DNA in Quantum Mechanics, and Nonlinear Biomechanics

First, based on the extensive quantum mechanics in biology, Schrödinger equation at column coordinates and its solution may derive the double helical structure of DNA. It is necessity mathematical conclusion that quantum mechanics has symmetry. Second, we discuss the nonlinear biomechanics, which is related to chaos, fractal and soliton, etc. Third, an important character of the nonlinear biosystems is the formation of self-organization, which should decrease entropy. Fourth, we propose the preliminary epidemic equations of COVID-19, and discuss their meaning. Complex biology provides a wide region for entropy decrease in various isolated systems.

NEPTUNE: Phase 3 Study of First-Line Durvalumab Plus Tremelimumab in Patients With Metastatic NSCLC

IntroductionNEPTUNE, a phase 3, open-label study, evaluated first-line durvalumab plus tremelimumab versus chemotherapy in metastatic NSCLC (mNSCLC). MethodsEligible patients with EGFR and ALK wild-type mNSCLC were randomized (1:1) to first-line durvalumab (20 mg/kg every 4 weeks until progression) plus tremelimumab (1 mg/kg every 4 weeks for up to four doses) or standard chemotherapy. Randomization was stratified by tumor programmed death-ligand 1 expression (≥25% versus <25%), tumor histologic type, and smoking history. The amended primary end point was overall survival (OS) in patients with blood tumor mutational burden (bTMB) greater than or equal to 20 mutations per megabase (mut/Mb). Secondary end points included progression-free survival (PFS) in patients with bTMB greater than or equal to 20 mut/Mb and safety and tolerability in all treated patients. ResultsAs of June 24, 2019, 823 patients were randomized (intention-to-treat [ITT]); 512 (62%) were bTMB-evaluable, with 129 of 512 (25%) having bTMB greater than or equal to 20 mut/Mb (durvalumab plus tremelimumab [n = 69]; chemotherapy [n = 60]). Baseline characteristics were balanced in the intention-to-treat. Among patients with bTMB greater than or equal to 20 mut/Mb, OS improvement with durvalumab plus tremelimumab versus chemotherapy did not reach statistical significance (hazard ratio 0.71 [95% confidence interval: 0.49–1.05; p = 0.081]; median OS, 11.7 versus 9.1 months); the hazard ratio for PFS was 0.77 (95% confidence interval, 0.51–1.15; median PFS, 4.2 versus 5.1 months). In the overall safety population, incidence of grade 3 or 4 treatment-related adverse events was 20.7% (durvalumab plus tremelimumab) and 33.6% (chemotherapy). ConclusionsNEPTUNE did not meet its primary end point of improved OS with durvalumab plus tremelimumab versus chemotherapy in patients with mNSCLC and bTMB greater than or equal to 20 mut/Mb. Despite the amended study design, with a resultant small primary analysis population, therapeutic activity was aligned with expectations based on mechanistic biology and previous studies.

RISING STARS: Heterogeneity and the tumor microenvironment in neuroendocrine prostate cancer.

Neuroendocrine prostate cancer, generally arising late in the disease trajectory, is a heterogeneous subtype that infers a worse prognosis and limited treatment options for patients. Characterization of the complex landscape of this disease subtype and scrutiny of the relationship between tumor cells and cells of the surrounding tumor microenvironment have aided in elucidating some of the mechanisms of neuroendocrine disease biology and have uncovered a multitude of signaling pathways involved in disease transdifferentiation under therapeutic selection. In this review, we discuss current efforts to better understand the heterogeneous landscape of neuroendocrine prostate cancer and summarize research efforts to define the interplay between tumor cells and the microenvironment, with an emphasis on the immune component. Research efforts have uncovered several potential therapeutic approaches that may improve disease outcomes for patients diagnosed with neuroendocrine prostate cancer, including the potential for combination immunotherapies. However, additional research is required to fully address and exploit the contribution of tumor cell and microenvironment heterogeneity in developing effective treatment strategies.

Immune repertoire and evolutionary trajectory analysis in the development of diabetic nephropathy.

Diabetic nephropathy (DN) is the leading cause of death and the greatest risk to the lives of people with advanced diabetes. Yet, the molecular mechanisms underlying its development and progression remain unknown. In this research, we studied the primary pathways driving DN using transcriptome sequencing and immune repertoire analysis. Firstly, we found that the diversity and abundance of the immune repertoire in late DN were significantly increased, while there was no significant change in early DN. Furthermore, B cell-mediated antibody responses may be the leading cause of DN progression. By analyzing master regulators, we found the key DN-driving transcription factors. In the late stage of DN, immune cells, fibroblasts, and epithelial cells were abundant, but other stromal cells were few. Early DN kidneys had a higher tissue stemness score than normal and advanced DN kidneys. We showed that DN progression involves proximal tubular metabolic reprogramming and stemness restoration using Monocle3. Through WGCNA, we found that co-expression modules that regulate DN progression and immune repertoire diversity mainly regulate immune-related signaling pathways. In addition, we also found that early DN had apparent activation of immune-related signaling pathways mainly enriched in immune cells. Finally, we found that activation of fibroblasts is typical of early DN. These results provide a research basis for further exploring the molecular biology and cellular mechanisms of the occurrence and development of DN and provide a theoretical basis for the prevention and treatment of DN.

Multimodality Molecular Imaging of Stem Cells Therapy of Myocardial Infarction

Stem cell therapy in patients with acute myocardial infarction promises a new exciting option. However, the long term fate of stem cells transplanted into myocardial is not clear. Molecular imaging play a vital role in tracking stem cells after intramyocardial delivery as well as in helping us understand the mechanisms of stem cell biology in vivo. In this review, we summarize the principles underlying four kinds of stem cells applied into myocardial infarction and the major tracking methods. Finally, we discuss that molecular imaging will be useful to the successful clinical implementation of this novel therapy.

Inhibition of DNAJC12 Inhibited Tumorigenesis of Rectal Cancer via Downregulating HSPA4 Expression.

Background Dysregulation of DnaJ heat shock protein family (HSP40) member C12 (DNAJC12) is implicated in the malignancy progression of multiple cancers. The current study aimed to determine the biology function and mechanism of DNAJC12 in rectal cancer (RC). Methods RC tissues, adjacent tissues, RC cell lines, and normal colorectal epithelial cell lines were collected to analyze DNAJC12 expression. The abilities of DNAJC12 on proliferation, migration, and apoptosis of RC cells were detected by CCK-8, wound healing, and flow cytometry assays. Co-IP assays were carried out to confirm the association between DNAJC12 and HSPA4. The effect of DNAJC12 on tumor growth was detected by using the xenograft model of nude mice. Results Elevation of DNAJC12 was uncovered in RC tissues and cell lines. DNAJC12 upregulation facilitated RC cell proliferation and migration and induced apoptosis, while DNAJC12 interference showed the opposite results. Besides, HSAP4 served as a potential binding protein for DNAJC12. Rescue experiments revealed that elevated of HSAP4 restored the impact of DNAJC12 silencing on the cell functions. Finally, DNAJC12 silencing hampered tumor growth of RC in vivo. Conclusion In summary, this study highlighted a key player of DNAJC12 in modulating the malignant biological progression of RC via DNAJC12/HSPA4 axis, displaying a potential therapeutic target for RC.

P480 A novel zincophore locus in Candida auris?

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Candida auris is an emerging multidrug-resistant human fungal pathogen that is spreading rapidly across the world and is associated with hospital-acquired invasive infections with high mortality rates. Whilst previous studies have focused on understanding the basic biology and drug resistance mechanisms of C. auris, nothing is known about the strategies underlying trace metal acquisition. Trace metals like zinc are known to be crucial for numerous biological functions across all kingdoms of life. Thus, in this study, we aimed to characterize the zinc uptake mechanisms of C. auris and determine their role in virulence. We compared the ability of C. auris to grow in zinc-restricted conditions with other pathogenic fungi belonging to the CTG and WGD clade. Regardless of the clade, we found that C. auris has a striking ability to grow under extreme zinc-limiting conditions when compared with other human pathogenic fungi. Other fungi have been demonstrated to scavenge zinc via a zincophore locus, encoding a secreted zinc-binding protein Pra1 and its cognate receptor, Zrt101. However, in silico analysis of C. auris revealed that this species has undergone a rearrangement of the locus. The canonical zincophore gene PRA1 has translocated to another chromosome and the extracellular zinc-binding domain of the Zrt101 receptor has undergone an inverted duplication generating a novel putative zincophore. Our qRT-PCR analysis demonstrated that both PRA1 and the novel zincophore genes were upregulated in response to neutral pH and zinc-restriction. Protein supernatant from C. auris strains also showed high zinc binding activity. Furthermore, we have generated mutants lacking the novel zincophore gene in C. auris by CRISPR/Cas9 and found that these deletion mutants exhibited perturbed growth under zinc limitation. Together our observations suggest that C. auris has evolved a unique zinc acquisition strategy from the environment and the host.

Cells in the mechanical spotlight

Brillouin microscopy, a technique that visualizes the transfer of energy from photons of light to phonons of mechanical energy (1), has emerged as a useful tool in the study of biological mechanics. Unlike other approaches to mechanical characterization, such as optical tweezers, atomic force microscopy (AFM), or rheology, Brillouin microscopy does not require physical contact between a probe and the specimen. Instead, the mechanical properties of the specimen are characterized by observing optical frequency shifts in the Brillouin scattered light from the specimen.

Understanding cell to cell communication in tumor microenvironment

The tumor microenvironment is an atmosphere that covers a tumor withinside the body. It consists of the extracellular matrix, immune cells, blood vessels, and different cells, like fibroblasts. Cell-to-cell communication is a vital procedure that continues the organic features and hemostasis of cells in microenvironmental, organs, and intact systems. The cell-to-cell communication complexity has been studied for many years and is now well-known because a part of the molecular mechanisms of complexity, organ disorder, and developmental biology. A tissue microenvironment of a growing tumor is constituted of the tumor stroma, proliferating tumor cells, infiltrating inflammatory cells, blood vessels, and quite a few related tissue cells. The tumor microenvironment offers all the vitamins, it desires to the tumor and also makes an area for the tumor to expand. Researchers are running to recognize its position in most cancer risk, improvement, and treatment. While therapeutically focused on the tumor microenvironment is an appealing method for the remedy of most cancers, current FDA-permitted remedies have restrained efficacy. Immune checkpoint blockade remedy changed into the primary era of antibody-primarily based cures to target immune cells withinside the microenvironment of tumor (PD1 and CTLA4).

Genetic structure and proteomic analysis associated in potato to Rhizoctonia solani AG-3PT-stem canker and black scurf

Rhizoctonia solani AG-3PT is a necrotrophic plant pathogenic fungus affecting potato production globally. A total of 20 isolates of R. solani AG-3PT were subjected to pathogenicity tests, genetic diversity and proteomic analyses. The genetic diversity of R. solani AG-3PT isolates with different disease virulence was analyzed using 11 simple sequence repeats (SSR) primer pairs. Cluster analysis grouped the isolates into five main categories, indicating a high genetic diversity and recombination among the isolates, with no correlation between the groups and geographical origin. The protein pattern of 20 isolates of R. solani AG-3PT with different disease severity were analyzed by SDS-PAGE. Protein profiles were different that maybe associated with different levels of their aggressiveness. Based on the pathogenicity test results, isolates Rs-13 and Rs-4 were classified as virulent and least virulent, respectively. Here, we used proteomics strategy to compare mycelial proteins of virulent and least virulent isolates in order to further characterize them at the molecular level. The 2-DE results showed a differential expression of 27 protein spots, of which 11 well-focused protein spots were subjected to LC-MS-MS. The functions of the identified proteins indicated that they play roles in the fungal development, sporulation, carbohydrate metabolic process, lipid metabolic process, protein modification, and nucleotide metabolic process. The differences in pathogenicity between Rs-13 and Rs-4 isolate can be explained by differences in the expression levels of proteins involved in these pathways. The results of this research can enrich our knowledge about the virulence strategies of R. solani AG-3PT and provide useful information for the development of future fungicides. A combination of genetic diversity assessments of pathogen and understanding the biology and virulence mechanisms of pathogen, can help us in development of innovative and sustainable approaches to slow down the emergence of pathogen.

Overview of the Heart’s Intelligence: A Dynamic Perspective Into the World of Energetic Wellness

Research over the last 30 years has begun to explore the intrinsic relationship between biology and quantum mechanics, leading to the new science of quantum biology. The convergence of these 2 seemingly disparate disciplines has revolutionized current thought on biophysiology and overall health and wellness. Important concepts covered in this review are the sensory and intuitive intelligence of the heart, the phenomenon of coherence, heart rate variability (HRV) and the creation of heart rhythms, the dynamic role of the autonomic nervous system (ANS), and the bidirectional communication network between the heart and the brain. Neurocardiology and psychoneurophysiology come into play, as well as electromagnetic fields (EMFs), biofield physiology, and quantum mechanics. This paper provides an overview of the heart as a physiological and sensory organ at the seat of innate intuitive intelligence. The energetic nature of the heart co-creates the ability to build resilience, and establishing emotional self-regulation is the basis for achieving systems-wide coherence and optimal states of wellbeing for people and those that surround them, both human and animal.

Discovering autoinhibition as a design principle for the control of biological mechanisms

Autoinhibition is a design principle realized in many molecular mechanisms in biology. After explicating the notion of a design principle and showing that autoinhibition is such a principle, we focus on how researchers discovered instances of autoinhibition, using research establishing the autoinhibition of the molecular motors kinesin and dynein as our case study. Research on kinesin and dynein began in the fashion described in accounts of mechanistic explanation but, once the mechanisms had been discovered, researchers discovered that they exhibited a second phenomenon, autoinhibition. The discovery of autoinhibition not only reverses the pattern in terms of which philosophers have understood mechanism discovery but runs counter to the one phenomenon-one mechanism principle assumed to relate mechanisms and the phenomena they explain. The ubiquity of autoinhibition as a design principle, therefore, necessitates a philosophical understanding of mechanisms that recognizes how they can participate in more than one phenomenon. Since mechanisms with this design are released from autoinhibition only when they are acted on by control mechanisms, we advance a revised account of mechanisms that accommodates attribution of multiple phenomena to the same mechanism and distinguishes them from other processes that control them.

The Role and Regulatory Mechanism of Brown Adipose Tissue Activation in Diet-Induced Thermogenesis in Health and Diseases

Brown adipose tissue (BAT) has been considered a vital organ in response to non-shivering adaptive thermogenesis, which could be activated during cold exposure through the sympathetic nervous system (SNS) or under postprandial conditions contributing to diet-induced thermogenesis (DIT). Humans prefer to live within their thermal comfort or neutral zone with minimal energy expenditure created by wearing clothing, making shelters, or using an air conditioner to regulate their ambient temperature; thereby, DIT would become an important mechanism to counter-regulate energy intake and lipid accumulation. In addition, there has been a long interest in the intriguing possibility that a defect in DIT predisposes one to obesity and other metabolic diseases. Due to the recent advances in methodology to evaluate the functional activity of BAT and DIT, this updated review will focus on the role and regulatory mechanism of BAT biology in DIT in health and diseases and whether these mechanisms are applicable to humans.

Delineating the role of extracellular vesicles in cancer metastasis: A comprehensive review.

Extracellular vesicles (EVs) are subcellular messengers that aid in the formation and spread of cancer by enabling tumor-stroma communication. EVs develop from the very porous structure of late endosomes and hold information on both the intrinsic “status” of the cell and the extracellular signals absorbed by the cells from their surroundings. These EVs contain physiologically useful components, including as nucleic acids, lipids, and proteins, which have been found to activate important signaling pathways in tumor and tumor microenvironment (TME) cells, aggravating tumor growth. We highlight critical cell biology mechanisms that link EVS formation to cargo sorting in cancer cells in this review.Sorting out the signals that control EVs creation, cargo, and delivery will aid our understanding of carcinogenesis. Furthermore, we reviewed how cancer development and spreading behaviors are affected by coordinated communication between malignant and non-malignant cells. Herein, we studied the reciprocal exchanges via EVs in various cancer types. Further research into the pathophysiological functions of various EVs in tumor growth is likely to lead to the discovery of new biomarkers in liquid biopsy and the development of tumor-specific therapies.

DNA Methyltransferases: From Evolution to Clinical Applications.

DNA methylation is an epigenetic mark that living beings have used in different environments. The MTases family catalyzes DNA methylation. This process is conserved from archaea to eukaryotes, from fertilization to every stage of development, and from the early stages of cancer to metastasis. The family of DNMTs has been classified into DNMT1, DNMT2, and DNMT3. Each DNMT has been duplicated or deleted, having consequences on DNMT structure and cellular function, resulting in a conserved evolutionary reaction of DNA methylation. DNMTs are conserved in the five kingdoms of life: bacteria, protists, fungi, plants, and animals. The importance of DNMTs in whether methylate or not has a historical adaptation that in mammals has been discovered in complex regulatory mechanisms to develop another padlock to genomic insurance stability. The regulatory mechanisms that control DNMTs expression are involved in a diversity of cell phenotypes and are associated with pathologies transcription deregulation. This work focused on DNA methyltransferases, their biology, functions, and new inhibitory mechanisms reported. We also discuss different approaches to inhibit DNMTs, the use of non-coding RNAs and nucleoside chemical compounds in recent studies, and their importance in biological, clinical, and industry research.

Trans-genetic effects of circular RNA expression quantitative trait loci and potential causal mechanisms in autism

Genetic risk variants and transcriptional expression changes in autism spectrum disorder (ASD) were widely investigated, but their causal relationship remains largely unknown. Circular RNAs (circRNAs) are abundant in brain and often serve as upstream regulators of mRNAs. By integrating RNA-sequencing with genotype data from autistic brains, we assessed expression quantitative trait loci of circRNAs (circQTLs) that cis-regulated expression of nearby circRNAs and trans-regulated expression of distant genes (trans-eGenes) simultaneously. We thus identified 3619 circQTLs that were also trans-eQTLs and constructed 19,804 circQTL-circRNA-trans-eGene regulatory axes. We conducted two different types of approaches, mediation and partial correlation tests (MPT), to determine the axes with mediation effects of circQTLs on trans-eGene expression through circRNA expression. We showed that the mediation effects of the circQTLs (trans-eQTLs) on circRNA expression were positively correlated with the magnitude of circRNA-trans-eGene correlation of expression profile. The positive correlation became more significant after adjustment for the circQTLs. Of the 19,804 axes, 8103 passed MPT. Meanwhile, we performed causal inference test (CIT) and identified 2070 circQTL-trans-eGene-ASD diagnosis propagation paths. We showed that the CIT-passing genes were significantly enriched for ASD risk genes, genes encoding postsynaptic density proteins, and other ASD-relevant genes, supporting the relevance of the CIT-passing genes to ASD pathophysiology. Integration of MPT- and CIT-passing axes further constructed 352 circQTL-circRNA-trans-eGene-ASD diagnosis propagation paths, wherein the circRNA-trans-eGene axes may act as causal mediators for the circQTL-ASD diagnosis associations. These analyses were also successfully applied to an independent dataset from schizophrenia brains. Collectively, this study provided the first framework for systematically investigating trans-genetic effects of circQTLs and inferring the corresponding causal relations in diseases. The identified circQTL-circRNA-trans-eGene regulatory interactions, particularly the internal modules that were previously implicated in the examined disorders, also provided a helpful dataset for further investigating causative biology and cryptic regulatory mechanisms underlying the neuropsychiatric diseases.

Mapping the global research landscape and hotspot of exercise therapy and chronic obstructive pulmonary disease: A bibliometric study based on the web of science database from 2011 to 2020.

Background: The application of exercise therapy (ET) in chronic obstructive pulmonary disease (COPD) is generating increasing clinical efficacy and social-economic value. In this study, research trends, evolutionary processes and hot topics in this field are detailed, as well as predictions of future development directions. Methods: Search for literature in the field of COPD and ET and analyze data to generate knowledge graphs using VOSiewer and CiteSpace software. The time frame for the search was from 2011 to January 2021. Then we extracted full-text key information (such as title, journal category, publication date, author, country and institution, abstract, and keyword) and obtained the co-citation analysis. Use hierarchal clustering analysis software developed by VOSviewer to map common citations, and use Citespace software to plot trend networks. Results: The United States topped the list with 27.91% of the number of articles posted, followed by the UK at 25.44%. Imperial College London was the highest number of article publications in institutions, followed by Maastricht University and the University of Toronto. The Royal Brompton Harefield NHS Foundation Trust was one of many research institutions and currently holds the highest average citations per item (ACI) value, followed by Imperial College London and the University of Leuven. Judging from the number of publications related to ET and COPD, it is mainly published in cell biology, respiratory pulmonary diseases, and rehabilitation experiments study medicine. The European Respiration Journal is the most widely published in this field, followed by the International Journal of Chronic Obstructive Pulmonary Disease and Respiratory Medicine. Conclusion: COPD combined with ET is widely used in clinical practice and is on the rise. A distinctive feature of the field is multidisciplinary integration. Rehabilitation research for COPD involves multidisciplinary collaboration, tissue engineering, and molecular biology mechanism studies to help patients remodel healthy breathing. Multidisciplinary rehabilitation measures provide a solid foundation for advancing clinical efficacy in the field of COPD.

The flowering transition pathways converge into a complex gene regulatory network that underlies the phase changes of the shoot apical meristem in Arabidopsis thaliana.

Post-embryonic plant development is characterized by a period of vegetative growth during which a combination of intrinsic and extrinsic signals triggers the transition to the reproductive phase. To understand how different flowering inducing and repressing signals are associated with phase transitions of the Shoot Apical Meristem (SAM), we incorporated available data into a dynamic gene regulatory network model for Arabidopsis thaliana. This Flowering Transition Gene Regulatory Network (FT-GRN) formally constitutes a dynamic system-level mechanism based on more than three decades of experimental data on flowering. We provide novel experimental data on the regulatory interactions of one of its twenty-three components: a MADS-box transcription factor XAANTAL2 (XAL2). These data complement the information regarding flowering transition under short days and provides an example of the type of questions that can be addressed by the FT-GRN. The resulting FT-GRN is highly connected and integrates developmental, hormonal, and environmental signals that affect developmental transitions at the SAM. The FT-GRN is a dynamic multi-stable Boolean system, with 223 possible initial states, yet it converges into only 32 attractors. The latter are coherent with the expression profiles of the FT-GRN components that have been experimentally described for the developmental stages of the SAM. Furthermore, the attractors are also highly robust to initial states and to simulated perturbations of the interaction functions. The model recovered the meristem phenotypes of previously described single mutants. We also analyzed the attractors landscape that emerges from the postulated FT-GRN, uncovering which set of signals or components are critical for reproductive competence and the time-order transitions observed in the SAM. Finally, in the context of such GRN, the role of XAL2 under short-day conditions could be understood. Therefore, this model constitutes a robust biological module and the first multi-stable, dynamical systems biology mechanism that integrates the genetic flowering pathways to explain SAM phase transitions.

New Numerical Approach for Solution of Nonlinear Differential Equations

Nonlinear differential equations extensively used mathematical models for many interesting and important phenomena observed in numerous areas of science and technology. They are inspired by problems in diverse fields such as economics, biology, fluid dynamics, physics, differential geometry, engineering, control theory, materials science, and quantum mechanics. This special issue aims to highlight recent developments in methods and applications of nonlinear differential equations. In addition, there are papers analyzing equations that arise in engineering, classical and fluid mechanics, and finance. In this paper, we present a new numerical approach, which is concerned with the solutions of Nonlinear Differential Equations determined by a new approximation system based on inverse Laplace transforms using Chebyshev polynomials functional matrix of integration. The obtained solutions are novel, and previous literature lacks such derivations. The reliability and accuracy of our approach were shown by comparing our derived solutions with solutions obtained by other existing methods. The efficiency of the proposed numerical technique is exhibited through graphical illustrations and results drafted in tabular form for specific values of the parameters to validate the numerical investigation. The system capability is clarified through several standard nonlinear differential equations: Duffing, Van der Pol, Blasius, and Haul. The numerical results illustrate that the estimated result is in good agreement with exact or numerical styles available in literature whenever the exact results are unknown. Errors estimation to the corresponding numerical scheme also is carried out.

SMARCB1-Deficient Cancers: Novel Molecular Insights and Therapeutic Vulnerabilities.

Simple SummaryLoss of SMARCB1 has been identified as the sole mutation in a number of rare pediatric and adult cancers, most of which have a poor prognosis despite intensive therapies including surgery, radiation, and chemotherapy. Thus, a more robust understanding of the mechanisms driving this set of cancers is vital to improving patient treatment and outcomes. This review outlines recent advances made in our understanding of the function of SMARCB1 and how these advances have been used to discover putative therapeutic vulnerabilities.SMARCB1 is a critical component of the BAF complex that is responsible for global chromatin remodeling. Loss of SMARCB1 has been implicated in the initiation of cancers such as malignant rhabdoid tumor (MRT), atypical teratoid rhabdoid tumor (ATRT), and, more recently, renal medullary carcinoma (RMC). These SMARCB1-deficient tumors have remarkably stable genomes, offering unique insights into the epigenetic mechanisms in cancer biology. Given the lack of druggable targets and the high mortality associated with SMARCB1-deficient tumors, a significant research effort has been directed toward understanding the mechanisms of tumor transformation and proliferation. Accumulating evidence suggests that tumorigenicity arises from aberrant enhancer and promoter regulation followed by dysfunctional transcriptional control. In this review, we outline key mechanisms by which loss of SMARCB1 may lead to tumor formation and cover how these mechanisms have been used for the design of targeted therapy.