• Alzheimer's disease
• H4R3me2a
• PI3K/AKT/GSK3β signaling
• PRMT3
• Primary age‐related tauopathy
• Tau hyperphosphorylation
• miR‐448

• 82471222 National Natural Science Foundation of China
• 92353302 National Natural Science Foundation of China
• CIFMS 2021-I2M-1-025 CAMS Innovation Fund for Medical Sciences
• 2021ZD0201100 STI2030-Major Project
• 3332024152 Fundamental Research Funds for the Central Universities

• SATB1
• cancer metastasis
• chromatin remodeling
• epithelial-mesenchymal transition (EMT)
• therapeutic strategies

• amphiregulin
• areca nut
• areca nut extract
• epithelial–mesenchymal transformation
• human oral keratinocyte

• Humans
• Cell Proliferation/drug effects
• Cell Movement/drug effects
• Epithelial-Mesenchymal Transition/drug effects
• Areca/chemistry
• Plant Extracts/pharmacology
• Keratinocytes/drug effects
• Keratinocytes/metabolism
• Epithelial Cells/drug effects
• MAP Kinase Signaling System/drug effects
• Nuts

• breast cancer
• drug resistance
• epithelial to mesenchymal transition
• metastasis
• transglutaminase 2

• Natural Science Foundation of Jilin Province
• First Hospital of Jilin University

• SATB1
• aging‐related diseases
• cellular senescence
• immunosenescence
• neurodegeneration

• Humans
• Cellular Senescence/genetics
• Matrix Attachment Region Binding Proteins/metabolism
• Matrix Attachment Region Binding Proteins/genetics
• Aging/genetics
• Aging/pathology
• Aging/metabolism
• Animals
• Neoplasms/genetics
• Neoplasms/pathology
• Neoplasms/metabolism
• Chromatin/metabolism
• Chromatin/genetics

• YDZJ202201ZYTS661 The Science and Technology Development Plan Project of Jilin Province

• chemoresistance
• hypoxia
• hypoxia-inducible factor (HIF)

• AMED-CREST21gm1110010s0203; P-PROMOTE22ama221417h0001 Japan Agency for Medical Research and Development
• JPJSCCA20200009; 18KK0241; 19K22595; 20H03621; 20H05033; 21KK0144; 21K19445; 23H02855; 21K07727 Japan Society for the Promotion of Science
• Research Grant Princess Takamatsu Cancer Research Fund
• Research Grant Uehara Memorial Foundation
• Research Grant Takeda Science Foundation
• Research Grant Ichiro Kanehara Foundation
• Research Grant Kobayashi Foundation for Cancer Research
• Research Grant Yasuda Medical Foundation
• Research Grant the Foundation for Promotion of Cancer Research
• Research Grant Suzuken (Japan)
• Research Grant Daiichi Sankyo Foundation of Life Science

• ascites-derived primary cultures
• chemoresistance
• epithelial–mesenchymal transition
• high-grade serous ovarian carcinoma
• transcriptomic signature

• Animals
• Mice
• Glioblastoma/genetics
• Endothelial Cells/pathology
• Cell Line, Tumor
• Macrophages
• Immunosuppression Therapy
• Brain Neoplasms/genetics

• R01 CA241501 NCI NIH HHS
• R01 HL155198 NHLBI NIH HHS
• R01 NS094533 NINDS NIH HHS
• R01 NS106108 NINDS NIH HHS
• National Institutes of Health
• Burroughs Wellcome Fund Career Award at the Scientific Interface
• University of Pennsylvania Institute for Translational Medicine and Therapeutics award
• National Institutes of Health Director’s New Innovator Award
• US National Science Foundation CAREER award

• cancer metastasis
• epigenetics
• tumor microenvironment
• tumorigenesis

• National Natural Science Foundation of China

• Breast cancer
• Non-coding RNAs
• Organs
• Pathways
• Subtypes
• Tumor cells
• Tumor microenvironment

• Humans
• Female
• Breast Neoplasms/pathology
• Tumor Microenvironment/genetics
• Melanoma
• Tropism
• Neoplasm Metastasis
• Melanoma, Cutaneous Malignant

• breast cancer
• chemoresistance
• micro RNA
• neoadjuvant (chemo)radiotherapy
• systemic therapies

• Indian Council of Medical Research

• Biomarkers
• Breast neoplasms
• Neoadjuvant therapy
• Neoplastic cells, circulating

• Cancer
• Machine learning
• Omics
• Precision medicine

• R01 CA200859 NCI NIH HHS

• 3D co-culture system
• bone metastasis
• drug screening
• interface tissue models
• nanofibrous scaffolds
• personalized medicine

• Humans
• Cisplatin
• Tumor Microenvironment
• Bone Neoplasms/metabolism
• Epithelial-Mesenchymal Transition
• Doxorubicin/pharmacology

• 171258 CIHR

• EMT
• arsenic
• cadmium
• carcinogenesis
• chromium
• metals
• microRNAs
• nickel

• R01 ES031402 NIEHS NIH HHS
• R01 ES031937 NIEHS NIH HHS
• R01CA216987 NIH HHS
• R01ES031402 NIH HHS
• R01CA213159 NIH HHS

•

Around 50–60% of microRNAs were significantly differentially expressed between ER- and ER + breast cancer cell lines.

The origin of cancer remains one of the most important enigmas in modern biology. This paper presents a hypothesis for the origin of carcinomas in which cellular aging and inflammation enable the recovery of cellular plasticity, which may ultimately result in cancer. The hypothesis describes carcinogenesis as the result of the dedifferentiation undergone by epithelial cells in hyperplasia due to replicative senescence towards a mesenchymal cell state with potentially cancerous behavior. In support of this hypothesis, the molecular, cellular, and histopathological evidence was critically reviewed and reinterpreted when necessary to postulate a plausible generic series of mechanisms for the origin and progression of carcinomas. In addition, the implications of this theoretical framework for the current strategies of cancer treatment are discussed considering recent evidence of the molecular events underlying the epigenetic switches involved in the resistance of breast carcinomas. The hypothesis also proposes an epigenetic landscape for their progression and a potential mechanism for restraining the degree of dedifferentiation and malignant behavior. In addition, the manuscript revisits the gradual degeneration of the nonalcoholic fatty liver disease to propose an integrative generalized mechanistic explanation for the involution and carcinogenesis of tissues associated with aging. The presented hypothesis might serve to understand and structure new findings into a more encompassing view of the genesis of degenerative diseases and may inspire novel approaches for their study and therapy.

Progress in detection and treatment have drastically improved survival for early breast cancer patients. However, distant recurrence causes high mortality and is typically considered incurable. Cancer dissemination occurs via circulating tumor cells (CTCs) and up to 75% of breast cancer patients could harbor micrometastatses at time of diagnosis, while metastatic recurrence often occurs years to decades after treatment. During clinical latency, disseminated tumor cells (DTCs) can enter a state of cell cycle arrest or dormancy at distant sites, and are likely shielded from immune detection and treatment. While this is a challenge, it can also be seen as an outstanding opportunity to target dormant DTCs on time, before their transformation into lethal macrometastatic lesions. Here, we review and discuss progress made in our understanding of DTC and dormancy biology in breast cancer. Strides in our mechanistic insights of these features has led to the identification of possible targeting strategies, yet, their integration into clinical trial design is still uncertain. Incorporating minimally invasive liquid biopsies and rationally designed adjuvant therapies, targeting both proliferating and dormant tumor cells, may help to address current challenges and improve precision cancer care.

Consistently, the high metastasis of cancer cells is the bottleneck in the process of tumor treatment. In this process of metastasis, a pivotal role is executed by epithelial–mesenchymal transition (EMT). The epithelial-to-mesenchymal transformation was first proposed to occur during embryonic development. Later, its important role in explaining embryonic developmental processes was widely reported. Recently, EMT and its intermediate state were also identified as crucial drivers in tumor progression with the gradual deepening of research. To gain insights into the potential mechanism, increasing attention has been focused on the EMT-related transcription factors. Correspondingly, miRNAs target transcription factors to control the EMT process of tumor cells in different types of cancers, while there are still many exciting and challenging questions about the phenomenon of microRNA regulation of cancer EMT. We describe the relevant mechanisms of miRNAs regulating EMT, and trace the regulatory roles and functions of major EMT-related transcription factors, including Snail, Twist, zinc finger E-box-binding homeobox (ZEB), and other families. In addition, on the basis of the complex regulatory network, we hope that the exploration of the regulatory relationship of non-transcription factors will provide a better understanding of EMT and cancer metastasis. The identification of the mechanism leading to the activation of EMT programs during diverse disease processes also provides a new protocol for the plasticity of distinct cellular phenotypes and possible therapeutic interventions. Here, we summarize the recent progress in this direction, with a promising path for further insight into this fast-moving field.

• Epithelial-mesenchymal transition. MicroRNAs. Breast cancer. Metastasis. cancer therapy

• anthracyclines
• breast cancer
• drug resistance
• efficacy
• miRNAs

• 5-Fluorouracil, Chemotherapy Sensitivity
• Breast cancer cells
• Paclitaxel
• ZEB1
• miR-448

• Breast Neoplasms
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Female
• Fluorouracil
• Gene Expression Regulation, Neoplastic
• Genes, Homeobox
• Humans
• MicroRNAs
• Neoplasm Invasiveness
• Paclitaxel
• Zinc Finger E-box-Binding Homeobox 1
• Zinc Fingers

Breast cancer (BC) is one of the commonly occurring malignancies in females worldwide. Despite significant advances in therapeutics, the mortality and morbidity of BC still lead to low survival and poor prognosis due to the drug resistance. There are certain chemotherapeutic, endocrine, and target medicines often used for BC patients, including anthracyclines, taxanes, docetaxel, cisplatin, and fluorouracil. The drug resistance mechanisms of these medicines are complicated and have not been fully elucidated. It was reported that non-coding RNAs (ncRNAs), such as micro RNAs (miRNA), long-chain non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) performed key roles in regulating tumor development and mediating therapy resistance. However, the mechanism of these ncRNAs in BC chemotherapeutic, endocrine, and targeted drug resistance was different. This review aims to reveal the mechanism and potential functions of ncRNAs in BC drug resistance and to highlight the ncRNAs as a novel target for achieving improved treatment outcomes for BC patients.

• breast cancer
• drug resistance
• long-chain non-coding RNA
• micro RNA
• non-coding RNA

• EMT
• LSCC
• NSCLC
• SATB1
• adenocarcinoma
• epithelial‑mesenchymal transition
• lung adenocarcinoma
• lung squamous cell carcinoma
• metastasis
• non‑small cell lung carcinoma
• special AT‑rich binding protein 1

• pancreatic carcinoma
• lncrna duxap8
• mir-448
• wtap
• fak
• pc ‐ pancreatic carcinoma
• lncrnas ‐ long noncoding rnas
• cerna ‐ competing endogenous rnas
• wtap ‐ wilms tumor 1–associating protein
• fak ‐ focal adhesion kinase
• mirnas ‐ micrornas
• atcc ‐ american type culture collection
• pbs ‐ phosphate-buffered saline
• qpcr ‐ quantitative polymerase chain reaction
• mmp ‐ matrix metallopeptidase

• Base Sequence
• Cell Cycle Proteins/genetics
• Cell Cycle Proteins/metabolism
• Cell Line
• Cell Line, Tumor
• Cell Movement/genetics
• Cell Proliferation/genetics
• Focal Adhesion Kinase 1/genetics
• Focal Adhesion Kinase 1/metabolism
• Gene Expression Regulation, Neoplastic
• HEK293 Cells
• Humans
• MicroRNAs/genetics
• Neoplasm Invasiveness
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology
• RNA Splicing Factors/genetics
• RNA Splicing Factors/metabolism
• RNA, Long Noncoding/genetics
• Sequence Homology, Nucleic Acid
• Signal Transduction/genetics

• PKCθ
• breast
• cancer stem cells
• miR-203

• SATB1
• cisplatin
• drug resistance
• lung cancer
• miR-448

Myotonic dystrophy type 1 (DM1), the most frequent inherited muscular dystrophy in adults, is caused by the CTG repeat expansion in the 3′UTR of the DMPK gene. Mutant DMPK RNA accumulates in nuclear foci altering diverse cellular functions including alternative splicing regulation. DM1 is a multisystemic condition, with debilitating central nervous system alterations. Although a defective neuroglia communication has been described as a contributor of the brain pathology in DM1, the specific cellular and molecular events potentially affected in glia cells have not been totally recognized. Thus, to study the effects of DM1 mutation on glial physiology, in this work, we have established an inducible DM1 model derived from the MIO-M1 cell line expressing 648 CUG repeats. This new model recreated the molecular hallmarks of DM1 elicited by a toxic RNA gain-of-function mechanism: accumulation of RNA foci colocalized with MBNL proteins and dysregulation of alternative splicing. By applying a microarray whole-transcriptome approach, we identified several gene changes associated with DM1 mutation in MIO-M1 cells, including the immune mediators CXCL10, CCL5, CXCL8, TNFAIP3, and TNFRSF9, as well as the microRNAs miR-222, miR-448, among others, as potential regulators. A gene ontology enrichment analyses revealed that inflammation and immune response emerged as major cellular deregulated processes in the MIO-M1 DM1 cells. Our findings indicate the involvement of an altered immune response in glia cells, opening new windows for the study of glia as potential contributor of the CNS symptoms in DM1.

• RNA foci
• gene expression
• inducible cell models
• microarrays
• myotonic dystrophy type 1

• 3' Untranslated Regions
• Alternative Splicing
• Cell Line
• Cell Nucleus/metabolism
• Central Nervous System/metabolism
• Exons
• Gene Expression Profiling
• Gene Expression Regulation
• Genotype
• Humans
• Immune System
• Inflammation
• Mutation
• Myotonic Dystrophy/genetics
• Myotonic Dystrophy/metabolism
• Myotonin-Protein Kinase/genetics
• Neuroglia/metabolism
• Oligonucleotide Array Sequence Analysis
• RNA/metabolism
• Transcriptome
• Trinucleotide Repeat Expansion

• breast cancer
• long non-coding rnas
• mirnas

• Chemoradiation resistance
• E-cadherin
• EMT
• MMP-9
• Nasopharyngeal carcinoma
• SATB1
• Vimentin

• BCL2
• BLC2
• adénome hypophysaire
• miR-448
• pituitary adenoma

• Adenoma/genetics
• Adenoma/metabolism
• Adenoma/pathology
• Apoptosis/physiology
• Cell Line, Tumor
• Cell Proliferation/physiology
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Pituitary Neoplasms/genetics
• Pituitary Neoplasms/metabolism
• Pituitary Neoplasms/pathology
• Proto-Oncogene Proteins c-bcl-2/genetics
• Proto-Oncogene Proteins c-bcl-2/metabolism
• Signal Transduction

Neoadjuvant chemotherapy (NCT) is the standard treatment for patients with locally advanced breast cancer (LABC). The aim of this study was to verify this relationship, and to estimate the clinical value of aneuploid circulating endothelial cells (CECs) in LABC patients with different NCT responses.

Breast cancer patients received an EC4-T4 NCT regimen. Peripheral blood mononuclear cells were obtained before NCT, and after the first and last NCT courses. A novel subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) strategy was applied for detection of circulating rare cells (CRCs). CECs (CD45–/CD31+/DAPI+) and circulating tumor cells (CTCs) with different cytogenetic abnormalities related to chromosome 8 aneuploidy were analyzed in LABC patients subjected to NCT.

A total of 41 patients were enrolled. Firstly, CD31+/EpCAM+ aneuploid endothelial-epithelial fusion cells were observed in LABC patients. Further, aneuploid CECs in the peripheral blood showed a biphasic response during NCT, as they initially increased and then decreased, whereas a strong positive correlation was observed between aneuploid CECs and CTC numbers.

We determined that aneuploid CEC dynamics vary in patients with different response to chemotherapy. Elucidating the potential cross-talk between CTCs and aneuploid CECs may help characterize the process associated with the development of chemotherapy resistance and metastasis.

• aneuploidy
• breast cancer
• circulating endothelial cells
• circulating tumor cells
• liquid biopsy
• neoadjuvant therapy

Gastric cancer (GC) is currently recognized as one of the most common and fatal tumor worldwide. The identification of novel biomarkers in relation to clinical information as well as extending the knowledge on a multiple crosstalk between various oncogenic pathways implicated in GC carcinogenesis seems pivotal to limit the disease-associated mortality. Therefore, we assessed the expression of HER2, NF-κB, and SATB1 in a total of 104 gastric adenocarcinomas and 30 normal gastric samples and correlated the expression patterns with each other and with some clinicopathological variables. Protein expression was examined by immunohistochemistry (IHC) on tissue microarrays (TMAs), and fluorescence in situ hybridization (FISH) was employed to detect HER2 amplification. In the studied group, HER2 and SATB1 were found to be overexpressed in gastric cancer tissue in comparison to normal gastric mucosa. The expression status of the former protein was seen to differ according to some clinicopathological features, but without statistical significance, whereas the expression of the latter was not importantly associated with any of them. In turn, the NF-κB protein level was significantly related to the presence of lymph node metastasis. HER2 expression was not significantly correlated with that of other proteins, but a positive correlation was found between the expression of SATB1 and NF-κB. Further studies with a larger group of patients combined with in vitro mechanistic experiments are required to fully elucidate the role and relationship of HER2, NF-κB, and SATB1 expression in gastric cancer progression. However, to the best of our knowledge, this study is the first look at a simultaneous evaluation of these three markers in the samples of gastric cancer patients.

• EMT
• SATB1
• Special AT-Rich Binding Protein 1
• cancer
• epidermal-mesenchymal transition
• metastasis

• Animals
• Cell Transformation, Neoplastic/genetics
• Cell Transformation, Neoplastic/metabolism
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Humans
• Matrix Attachment Region Binding Proteins/genetics
• Matrix Attachment Region Binding Proteins/metabolism
• Neoplasm Metastasis
• Neoplasms/etiology
• Neoplasms/metabolism
• Neoplasms/pathology
• Signal Transduction

• cell migration
• cell proliferation
• microRNA-448
• non-small-cell lung cancer
• sirtuin1

• Animals
• Carcinogenesis
• Chromatin/metabolism
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Humans
• Matrix Attachment Region Binding Proteins/metabolism
• Neoplasms/immunology
• Neoplasms/metabolism
• Neoplasms/pathology

• breast cancer
• ceRNA
• ceRNET
• ceRnome
• ncRNAs

• MiR-448
• TLR4
• lipopolysaccharide
• macrophages
• type 2 diabetes mellitus

• Sine oculis homeobox homolog 1 (Six1)
• airway remodeling
• asthma
• epithelial-mesenchymal transition (EMT)
• microRNA-448-5p

• Biomarkers
• Breast cancer
• Micro RNAs
• Prognostic
• Therapy predictive

• Metastasis
• cancer
• epithelial-to-mesenchymal transition
• microRNA-10b

• R01 CA163461 NCI NIH HHS
• R25 CA174650 NCI NIH HHS
• R01 CA221771 NCI NIH HHS
• R01 CA135650 NCI NIH HHS
• R56 CA214464 NCI NIH HHS

• Breast cancer
• IDO
• SNHG1
• Treg cell
• miR-448

• NEAT1
• ZEB1
• breast cancer
• miR-448

The NF-κB family of transcription factors regulate the expression of genes encoding proteins and microRNAs (miRNA, miR) precursors that may either positively or negatively regulate a variety of biological processes such as cell cycle progression, cell survival, and cell differentiation. The NF-κB-miRNA transcriptional regulatory network has been implicated in the regulation of proinflammatory, immune, and stress-like responses. Gene regulation by miRNAs has emerged as an additional epigenetic mechanism at the post-transcriptional level. The expression of miRNAs can be regulated by specific transcription factors (TFs), including the NF-κB TF family, and vice versa. The interplay between TFs and miRNAs creates positive or negative feedback loops and also regulatory networks, which can control cell fate. In the current review, we discuss the impact of NF-κB-miRNA interplay and feedback loops and networks impacting on inflammation in cancer. We provide several paradigms of specific NF-κB-miRNA networks that can regulate inflammation linked to cancer. For example, the NF-κB-miR-146 and NF-κB-miR-155 networks fine-tune the activity, intensity, and duration of inflammation, while the NF-κB-miR-21 and NF-κB-miR-181b-1 amplifying loops link inflammation to cancer; and p53- or NF-κB-regulated miRNAs interconnect these pathways and may shift the balance to cancer development or tumor suppression. The availability of genomic data may be useful to verify and find novel interactions, and provide a catalogue of 162 miRNAs targeting and 40 miRNAs possibly regulated by NF-κB. We propose that studying active TF-miRNA transcriptional regulatory networks such as NF-κB-miRNA networks in specific cancer types can contribute to our further understanding of the regulatory interplay between inflammation and cancer, and also perhaps lead to the development of pharmacologically novel therapeutic approaches to combat cancer.

• NF-κB
• cancer
• inflammation
• miRNAs
• oncogenic and tumor suppressor pathways
• transcriptional regulatory networks

Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related mortality; nevertheless, there are few data regarding detection of circulating tumor cells (CTCs) in NSCLC, compared to other kinds of cancers in which their prognostic roles have already been defined. This difference is likely due to detection methods based on the epithelial marker expression which ignore CTCs undergoing epithelial-mesenchymal transition (CTCs^EMT).

After optimization of the test with spiking experiments of A549 cells undergoing TGF-β1-induced EMT (A549^EMT), the CTCs^EMT were enriched by immunomagnetic depletion of leukocytes and then characterized by a RT-PCR assay based on the retrieval of epithelial and EMT-related genes. Blood samples from ten metastatic NSCLC patients before starting treatment and during chemotherapy were used to test this approach by longitudinal monitoring. Ten age- and sex-matched healthy subjects were also enrolled as controls.

Recovery experiments of spiked A549^EMT cells showed that the RT-PCR assay is a reliable method for detection of CTCs^EMT. CTCs^EMT were detected in three patients at baseline and in six patients after four cycles of cysplatin-based chemotherapy. Longitudinal monitoring of three patients showed that the CTCs^EMT detection is related to poor therapeutic response.

The RT-PCR-based approach for the evaluation of CTCs^EMT phenotype could be a promising and inexpensive tool to predict the prognosis and the therapeutic response in NSCLC patients.

• Cancer
• cell
• disease
• microRNA
• molecular
• oncogenesis