• cancer therapy
• prognostic markers

• Humans
• Wnt Signaling Pathway/genetics
• Neoplasms/genetics
• Neoplasms/pathology
• Neoplasms/metabolism
• Wnt Proteins/genetics
• Neurodegenerative Diseases/genetics
• Neurodegenerative Diseases/pathology
• Neurodegenerative Diseases/metabolism
• Animals
• Autoimmune Diseases/genetics
• Autoimmune Diseases/pathology
• Autoimmune Diseases/metabolism
• Cardiovascular Diseases/genetics
• Cardiovascular Diseases/metabolism
• Cardiovascular Diseases/pathology
• beta Catenin/genetics

• 82200673 National Natural Science Foundation of China (National Science Foundation of China)
• This work was supported by the Opening Foundation of the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine (SKLID2024KF01) and the National Nature Science Foundation of China (82200673).

• Humans
• Female
• Endometrial Neoplasms/genetics
• Haplotypes/genetics
• Genome-Wide Association Study
• Sweden
• Polymorphism, Single Nucleotide
• Genetic Predisposition to Disease
• Case-Control Studies
• Middle Aged
• Risk Factors
• Genetic Loci
• Aged

• ABC transporters
• Anticancer drugs
• Cancer
• Multidrug resistance

• Humans
• Neoplasms/drug therapy
• Neoplasms/metabolism
• Neoplasms/genetics
• Neoplasms/pathology
• Drug Resistance, Neoplasm/genetics
• ATP-Binding Cassette Transporters/metabolism
• ATP-Binding Cassette Transporters/genetics
• Drug Resistance, Multiple/genetics
• Antineoplastic Agents/therapeutic use
• Antineoplastic Agents/pharmacology
• Animals
• Neoplasm Proteins/metabolism
• Neoplasm Proteins/genetics

• ABC transporter
• chemoresisitance
• doxorubicin
• miRNA - microRNA
• ncRNA

• ADME
• Breast cancer
• Immune microenvironment
• Immunotherapy
• Prognosis

• Humans
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Breast Neoplasms/drug therapy
• Breast Neoplasms/pathology
• Female
• Prognosis
• Nomograms
• Gene Expression Regulation, Neoplastic
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Gene Expression Profiling
• Tumor Microenvironment
• Middle Aged
• Transcriptome

• ABC transporter
• cancer stem cells
• half-transporter
• multidrug resistance

• cancer stem cells
• cancer therapy

• Humans
• Neoplastic Stem Cells/pathology
• Neoplastic Stem Cells/metabolism
• Neoplasms/therapy
• Neoplasms/genetics
• Neoplasms/pathology
• Neoplasms/metabolism
• Signal Transduction
• Drug Resistance, Neoplasm/genetics

• Advanced Lung Cancer Targeted Therapy Research Foundation of China (CTONG-YC20210303) Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province (CXPJJH121005-01) National Multidisciplinary Cooperative Diagnosis and Treatment Capacity (lung cancer z027002) Health Research Project of Hunan Provincial Health Commission (W20242005) Postdoctoral Fellowship Program of CPSF (GZC20233187)

• Humans
• Axl Receptor Tyrosine Kinase
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/metabolism
• Proto-Oncogene Proteins/metabolism
• Proto-Oncogene Proteins/antagonists & inhibitors
• Receptor Protein-Tyrosine Kinases/metabolism
• Receptor Protein-Tyrosine Kinases/antagonists & inhibitors
• Animals
• Molecular Targeted Therapy
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Epithelial-Mesenchymal Transition
• Drug Resistance, Neoplasm

• prognostic
• skin cutaneous melanoma
• tcga
• vasculogenic mimicry

• Humans
• Melanoma/genetics
• Skin Neoplasms/genetics
• Prognosis
• Drug Delivery Systems
• Risk Factors
• Tumor Microenvironment

• Cancer stem cell
• Clinical treatment
• Exosome
• Immune
• PD-1

• Humans
• Mesenchymal Stem Cells/pathology
• Tumor Microenvironment
• Neoplasms/drug therapy
• Immunotherapy
• Neoplastic Stem Cells

• Animals
• Female
• Mice
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics
• ATP-Binding Cassette Transporters/genetics
• ATP-Binding Cassette Transporters/metabolism
• Brain Neoplasms/drug therapy
• Breast Neoplasms/drug therapy
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Drug Resistance, Neoplasm/genetics
• Endothelial Cells/metabolism
• Neoplasm Proteins/metabolism

• Baxter International
• H2020 European Research Council
• FP7 Ideas
• Department of Health
• GABBA Program
• CancerGenomiCs.nl
• Human Frontier Science Program
• Medical Research Council Canada
• Courant Forschungszentrum Geobiologie, Georg-August-Universität Göttingen
• National Health and Medical Research Council
• Swiss National Science Foundation

• Cancer stem cells
• Patient-derived organoids
• Pre-clinical cancer models
• Therapy resistance
• Tissue-specific cancer stem cell markers

Colorectal cancer (CRC) remains the third most prevalent cancer disease and involves a multi-step process in which intestinal cells acquire malignant characteristics. It is well established that the appearance of distal metastasis in CRC patients is the cause of a poor prognosis and treatment failure. Nevertheless, in the last decades, CRC aggressiveness and progression have been attributed to a specific cell population called CRC stem cells (CCSC) with features like tumor initiation capacity, self-renewal capacity, and acquired multidrug resistance. Emerging data highlight the concept of this cell subtype as a plastic entity that has a dynamic status and can be originated from different types of cells through genetic and epigenetic changes. These alterations are modulated by complex and dynamic crosstalk with environmental factors by paracrine signaling. It is known that in the tumor niche, different cell types, structures, and biomolecules coexist and interact with cancer cells favoring cancer growth and development. Together, these components constitute the tumor microenvironment (TME). Most recently, researchers have also deepened the influence of the complex variety of microorganisms that inhabit the intestinal mucosa, collectively known as gut microbiota, on CRC. Both TME and microorganisms participate in inflammatory processes that can drive the initiation and evolution of CRC. Since in the last decade, crucial advances have been made concerning to the synergistic interaction among the TME and gut microorganisms that condition the identity of CCSC, the data exposed in this review could provide valuable insights into the biology of CRC and the development of new targeted therapies.

• Colorectal cancer
• Colorectal cancer stem cells
• Tumor microenvironment factors
• Tumor stroma
• Gut microbiota
• Cancer progression

• Cancer anticancer strategy
• Cancer stem cells
• Exosomes
• The tumor microenvironment
• Therapeutic target

• R01DE028351 NIDCR NIH HHS
• R03DE032084 NIDCR NIH HHS

• Colorectal cancer
• Drug-resistance
• Metastatic colorectal cancer
• Personalized medicine
• Targeted therapy

• Humans
• Vascular Endothelial Growth Factor A
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Antineoplastic Agents/therapeutic use
• Prognosis
• Molecular Targeted Therapy
• Receptor, ErbB-2
• Neoplasm Metastasis/drug therapy

• Drug resistance
• Genome-scale metabolic network model
• Metabolomics
• Na+ homeostasis
• Plasmodium falciparum
• Transcriptomics

• Animals
• Parasites
• Antimalarials/therapeutic use
• Malaria/drug therapy
• Malaria, Falciparum/parasitology
• Plasmodium falciparum
• Phospholipids/metabolism
• Phospholipids/therapeutic use

• T32 AI138953 NIAID NIH HHS
• R01 AI154499 NIAID NIH HHS
• W81XWH-14-2-0134 U.S. Army Medical Research and Development Command
• R01 AI125534 NIAID NIH HHS
• R01 AI132508 NIAID NIH HHS
• W81XWH-15-C-0061 U.S. Army Medical Research and Development Command
• R01 AI098413 NIAID NIH HHS
• National Institutes of Health Grant

• ABCB5
• advanced-therapy medicinal product
• angiogenesis
• cell therapy
• chronic wound
• epidermolysis bullosa
• immunomodulation
• inflammation
• mesenchymal stem cells
• wound healing

• United States
• Humans
• Mesenchymal Stem Cells/metabolism
• Epidermolysis Bullosa Dystrophica/metabolism
• Germany
• ATP Binding Cassette Transporter, Subfamily B/metabolism

• 1R01HL161087 NHLBI NIH HHS
• R24 EY028767 NEI NIH HHS
• R01 EY025794 NEI NIH HHS
• RO1EY025794 NEI NIH HHS
• P01 AG071463 NIA NIH HHS
• R24EY028767 NEI NIH HHS
• R01 HL161087 NHLBI NIH HHS

• 5-FU
• Colorectal cancer
• Regulation
• Resistance
• Thymidylate synthase

• ABCB5
• Epithelial to Mesenchymal Transition
• Limbal epithelial stem cells
• Limbal niche
• UV irradiation

Tumor recurrence and chemotherapy resistance are mainly responsible for poor prognosis in colorectal cancer (CRC) patients. Cancer stem cell (CSC) has been identified in many solid tumors, including CRC. Additionally, CSC cannot be completely killed during chemotherapy and develops resistance to chemotherapeutic drugs, which is the main reason for tumor recurrence. This study reviews the main mechanisms of CSC chemotherapy resistance in CRC, including activation of DNA damage checkpoints, epithelial-mesenchymal transition (EMT), inhibition of the overexpression of antiapoptotic regulatory factors, overexpression of ATP-binding cassette (ABC) transporters, maintenance of reactive oxygen species (ROS) levels, and the dormant state of CSC. Advances in research to reverse chemotherapy resistance are also discussed. Our study can provide the promising potential for eliminating CSC and preventing tumor progression for CRC treatment.

• Department of Finance of Jilin Province

• Bcl-2 family
• Cancer stem cells (CSCs)
• anti-apoptotic proteins
• apoptosis
• c-FLIP
• death receptor pathways
• drug resistance

• R01 CA080734 NCI NIH HHS
• R01 CA090878 NCI NIH HHS
• R01 CA101743 NCI NIH HHS

• ABCB5
• melanocyte biology
• melanoma

Unstable carotid stenosis is an important cause of ischemic stroke, yet the basis of disease pathophysiology remains largely unknown. We hypothesized that integrated analyses of symptomatic carotid stenosis patients at increased stroke risk stratified by clinical scores, CAR and ABCD2, with transcriptomic and clinical data could improve identification of molecular pathways and targets for instability. We show that high CAR score reflects plaque instability processes related to intra-plaque hemorrhage, angiogenesis, inflammation, and foam cell differentiation, whereas ABCD2 associates with neutrophil-mediated immunity, foam cell differentiation, cholesterol transport, and coagulation. Repressed processes in plaques from high-risk patients were ossification, chondrocyte differentiation, SMC migration, and ECM organization. ABCB5 gene was found as the top upregulated in high-risk patient’s plaques, localized to macrophages in areas with neovascularization and intra-plaque hemorrhage. The link between ABCB5 and intra-plaque hemorrhage suggests its key role for plaque instability that warrants further exploration.

•

We integrated stroke risk in carotid stenosis patients with plaque transcriptomics

• Cell biology
• Health sciences
• Transcriptomics

• bioinformatics
• colorectal cancer
• gut microbiome
• ontology
• reverse microbiomics
• reverse vaccinology

Although rare, uveal melanoma (UM) is the most common cancer that develops inside adult eyes. The prognosis is poor, since 50% of patients will develop lethal metastases in the first decade, especially to the liver. Once metastases are detected, life expectancy is limited, given that the available treatments are mostly unsuccessful. Thus, there is a need to find methods that can accurately predict UM prognosis and also effective therapeutic strategies to treat this cancer. In this manuscript, we initially compile the current knowledge on epidemiological, clinical, pathological and molecular features of UM. Then, we cover the most relevant prognostic factors currently used for the evaluation and follow-up of UM patients. Afterwards, we highlight emerging molecular markers in UM published over the last three years. Finally, we discuss the problems preventing meaningful advances in the treatment and prognostication of UM patients, as well as forecast new roadblocks and paths of UM-related research.

Uveal melanoma (UM) is the most common malignant intraocular tumour in the adult population. It is a rare cancer with an incidence of nearly five cases per million inhabitants per year, which develops from the uncontrolled proliferation of melanocytes in the choroid (≈90%), ciliary body (≈6%) or iris (≈4%). Patients initially present either with symptoms like blurred vision or photopsia, or without symptoms, with the tumour being detected in routine eye exams. Over the course of the disease, metastases, which are initially dormant, develop in nearly 50% of patients, preferentially in the liver. Despite decades of intensive research, the only approach proven to mildly control disease spread are early treatments directed to ablate liver metastases, such as surgical excision or chemoembolization. However, most patients have a limited life expectancy once metastases are detected, since there are limited therapeutic approaches for the metastatic disease, including immunotherapy, which unlike in cutaneous melanoma, has been mostly ineffective for UM patients. Therefore, in order to offer the best care possible to these patients, there is an urgent need to find robust models that can accurately predict the prognosis of UM, as well as therapeutic strategies that effectively block and/or limit the spread of the metastatic disease. Here, we initially summarized the current knowledge about UM by compiling the most relevant epidemiological, clinical, pathological and molecular data. Then, we revisited the most important prognostic factors currently used for the evaluation and follow-up of primary UM cases. Afterwards, we addressed emerging prognostic biomarkers in UM, by comprehensively reviewing gene signatures, immunohistochemistry-based markers and proteomic markers resulting from research studies conducted over the past three years. Finally, we discussed the current hurdles in the field and anticipated the future challenges and novel avenues of research in UM.

• biomarkers
• metastases
• molecular pathology
• prognostic factors
• survival
• uveal melanoma

Understanding the genomic alterations in oral carcinogenesis remains crucial for the appropriate diagnosis and treatment of oral squamous cell carcinoma (OSCC). To unveil the mutational spectrum, in this study, we conducted whole-exome sequencing (WES), using six mutation calling pipelines and multiple filtering criteria applied to 50 paired OSCC samples. The tumor mutation burden extracted from the data set of somatic variations was significantly associated with age, tumor staging, and survival. Several genes (MUC16, MUC19, KMT2D, TTN, HERC2) with a high frequency of false positive mutations were identified. Moreover, known (TP53, FAT1, EPHA2, NOTCH1, CASP8, and PIK3CA) and novel (HYDIN, ALPK3, ASXL1, USP9X, SKOR2, CPLANE1, STARD9, and NSD2) genes have been found to be significantly and frequently mutated in OSCC. Further analysis of gene alteration status with clinical parameters revealed that canonical pathways, including clathrin-mediated endocytotic signaling, NFκB signaling, PEDF signaling, and calcium signaling were associated with OSCC prognosis. Defining a catalog of targetable genomic alterations showed that 58% of the tumors carried at least one aberrant event that may potentially be targeted by approved therapeutic agents. We found molecular OSCC subgroups which were correlated with etiology and prognosis while defining the landscape of major altered events in the coding regions of OSCC genomes. These findings provide information that will be helpful in the design of clinical trials on targeted therapies and in the stratification of patients with OSCC according to therapeutic efficacy.

• mutation burden
• oral cancer
• somatic mutation
• survival
• whole-exome sequencing

AXL is a member of the TAM (TYRO3, AXL, MER) family of receptor tyrosine kinases. In normal physiological conditions, AXL is involved in removing dead cells and their remains, and limiting the duration of immune responses. Both functions are utilized by cancers in the course of tumour progression. Cancer cells use the AXL pathway to detect toxic environments and to activate molecular mechanisms, thereby ensuring their survival or escape from the toxic zone. AXL is instrumental in controlling genetic programs of epithelial-mesenchymal and mesenchymal-epithelial transitions, enabling cancer cells to metastasize. Additionally, AXL signaling suppresses immune responses in tumour microenvironment and thereby helps cancer cells to evade immune surveillance. The broad role of AXL in tumour biology is the reason why its inhibition sensitizes tumours to a broad spectrum of anti-cancer drugs. In this review, we outline molecular mechanisms underlying AXL function in normal tissues, and discuss how these mechanisms are adopted by cancers to become metastatic and drug-resistant.

The TAM proteins TYRO3, AXL, and MER are receptor tyrosine kinases implicated in the clearance of apoptotic debris and negative regulation of innate immune responses. AXL contributes to immunosuppression by terminating the Toll-like receptor signaling in dendritic cells, and suppressing natural killer cell activity. In recent years, AXL has been intensively studied in the context of cancer. Both molecules, the receptor, and its ligand GAS6, are commonly expressed in cancer cells, as well as stromal and infiltrating immune cells. In cancer cells, the activation of AXL signaling stimulates cell survival and increases migratory and invasive potential. In cells of the tumour microenvironment, AXL pathway potentiates immune evasion. AXL has been broadly implicated in the epithelial-mesenchymal plasticity of cancer cells, a key factor in drug resistance and metastasis. Several antibody-based and small molecule AXL inhibitors have been developed and used in preclinical studies. AXL inhibition in various mouse cancer models reduced metastatic spread and improved the survival of the animals. AXL inhibitors are currently being tested in several clinical trials as monotherapy or in combination with other drugs. Here, we give a brief overview of AXL structure and regulation and discuss the normal physiological functions of TAM receptors, focusing on AXL. We present a theory of how epithelial cancers exploit AXL signaling to resist cytotoxic insults, in order to disseminate and relapse.

• AXL
• TAM receptors
• drug resistance
• epithelial-mesenchymal plasticity
• metastasis

• Cancer Stem Cells
• Colorectal Cancer
• Intra-Tumor Heterogeneity
• Omic Technologies
• Single-Cell Analyses
• Targeted Therapies

• OCT4
• SORE6xreporter
• cancer stem-like cells
• colon cancer
• intrinsic disorder predisposition analysis
• mRNA seq

• Adenocarcinoma/genetics
• Adenocarcinoma/pathology
• Adult
• Biomarkers, Tumor/isolation & purification
• Cell Culture Techniques/methods
• Cell Cycle
• Cell Line, Tumor
• Cell Movement/genetics
• Cell Proliferation/genetics
• Colonic Neoplasms/genetics
• Colonic Neoplasms/pathology
• Female
• Gene Expression Regulation, Neoplastic/genetics
• Humans
• Male
• Middle Aged
• Neoplastic Stem Cells/metabolism
• Neoplastic Stem Cells/pathology
• Octamer Transcription Factor-3/genetics
• Octamer Transcription Factor-3/metabolism
• Primary Cell Culture
• SOXB1 Transcription Factors/genetics
• SOXB1 Transcription Factors/metabolism

• The work was partially supported by the Institute of Cytology Director's Fund for S.A.K., E.N.T., M.A.B., V.A.P., O.V.A. and A.E.V.

Studies with biomarkers in TMA (tissue microarray) have been showing important results regarding its expression in colon cancer.

Correlate the expression profile of the OPN and ABCB5 biomarkers with the epidemiological and clinicopathological characteristics of the patients, the impact on the progression of the disease and the death.

A total of 122 CRC patients who underwent surgical resection, immunomarking and their relationship with progression and death events were evaluated.

The average age was 61.9 (±13.4) years. The cases were distributed in 42 (35.9%) in the ascending/transverse colon, 31 (26.5%) in the sigmoid, 27 in the rectum (23.1%), 17 (14.5%) in the descending colon. Most patients had advanced disease (stages III and IV) in 74 cases (60.9%). There was a predominance of moderately differentiated tumors in 101 samples (82.8%); despite this, the poorly differentiated subtype proved to be an independent risk factor for death in 70%. Metastasis to the liver proved to be an independent risk factor for death in 75% (18/24), as well as patients with primary rectal tumors in 81.5% (22/27).

The immunohistochemical expression of the OPN and ABCB5 markers was not associated with epidemiological and clinicopathological characteristics. Regarding the progression of disease and death, it was not possible to observe a correspondence relationship with the evaluated markers.

• ABC transporter
• Full-length ABCB5 transporter
• Molecular docking
• Molecular dynamics simulations
• Molecular modelling

• ABC transporter
• breast cancer
• competitive allele-specific PCR
• disease-free survival
• next-generation sequencing
• therapy response

• ATP-Binding Cassette Transporters/genetics
• Alleles
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Biomarkers, Tumor
• Breast Neoplasms/diagnosis
• Breast Neoplasms/genetics
• Breast Neoplasms/mortality
• Breast Neoplasms/therapy
• Female
• Gene Frequency
• Genetic Variation
• Genotype
• High-Throughput Nucleotide Sequencing
• Humans
• Kaplan-Meier Estimate
• Neoadjuvant Therapy
• Polymorphism, Single Nucleotide
• Prognosis
• Quantitative Trait Loci
• Treatment Outcome

Expression of CD133 and ABCB5 is associated with tumor aggressiveness, but evidence in papillary thyroid cancer (PTC) is lacking. We correlated CD133 and ABCB5 expression with pathological characteristics and factors of worse prognosis in PTC. Samples of 119 PTCs and 40 controls (goiters) were distributed in 8 tissue microarray blocks and evaluated with immunohistochemistry using anti-CD133 and anti-ABCB5 antibodies. The expression of each marker alone and combined was analyzed against pathological characteristics and factors of worse prognosis in PTC. Expression of CD133 alone (19 tumors, 16.0%) was more frequent in patients with versus without lymph node metastases (P=0.024). Expression of ABCB5 alone (n=95, 83.3%) was associated with larger tumor size (P=0.045). CD133-ABCB5 coexpression was not associated with pathological characteristics or factors of worse prognosis in PTC.

• ABC transporters
• Cancer
• Multidrug resistance
• P-glycoprotein
• Prognostic factor
• Survival analysis

• Chemoresistance
• Colorectal cancer
• miRNA

• Bcl-2 family
• anti-apoptotic proteins
• apoptosis
• c-FLIP
• cancer stem cells (CSCs)
• death receptor pathways
• drug resistance

• R01 CA080734 NCI NIH HHS
• R01 CA090878 NCI NIH HHS
• R01 CA101743 NCI NIH HHS

• ATP-binding cassette subfamily B member 5 (ABCB5)
• CD133
• anticancer drug
• apoptosis
• cancer stem cells
• cell cycle
• chemoresistance
• glioblastoma
• glioblastoma multiforme
• temozolomide
• tumor marker

• ATP Binding Cassette Transporter, Subfamily B/antagonists & inhibitors
• ATP Binding Cassette Transporter, Subfamily B/genetics
• ATP Binding Cassette Transporter, Subfamily B/metabolism
• Animals
• Antibodies, Neoplasm/pharmacology
• Apoptosis/drug effects
• Brain Neoplasms/drug therapy
• Brain Neoplasms/genetics
• Brain Neoplasms/metabolism
• Brain Neoplasms/pathology
• Cell Line, Tumor
• Drug Resistance, Neoplasm/drug effects
• Drug Resistance, Neoplasm/genetics
• Female
• G2 Phase Cell Cycle Checkpoints/drug effects
• Glioblastoma/drug therapy
• Glioblastoma/genetics
• Glioblastoma/metabolism
• Glioblastoma/pathology
• Humans
• M Phase Cell Cycle Checkpoints/drug effects
• Mice
• Neoplasm Proteins/antagonists & inhibitors
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• RNA, Small Interfering/genetics
• RNA, Small Interfering/pharmacology
• Temozolomide/pharmacology
• Xenograft Model Antitumor Assays

• I01 BX000516 BLRD VA
• R01 CA113796 NCI NIH HHS
• R24 EY028767 NEI NIH HHS
• R01 CA138231 NCI NIH HHS
• T32 EB016652 NIBIB NIH HHS
• R01 CA158467 NCI NIH HHS
• R01 EY025794 NEI NIH HHS
• I01 RX000989 RRD VA
• U.S. Department of Veterans Affairs (VA)
• DOD | United States Army | MEDCOM | CDMRP | DOD Peer Reviewed Cancer Research Program (PRCRP)
• HHS | NIH | National Cancer Institute (NCI)
• HHS | NIH | National Eye Institute (NEI)
• HHS | National Institutes of Health

Accumulating studies have indicated that long non-coding RNAs (lncRNAs) participate in the regulation of cancer stem cells (CSCs), which are crucial in tumor initiation, metastasis, relapse, and therapy resistance. In the current study, RT-PCR analysis was employed to evaluate the expression of LINC00963 in tumor tissues and oral CSCs. Stemness phenotypes and the expression of CSCs markers in oral cancer cells transfected with sh-LINC00963 were examined. Our results showed that the expression of the lncRNA LINC00963 was up-regulated in oral cancer tissues and CSCs. We found that the downregulation of LINC00963 inhibited CSC hallmarks, such as migration, invasion and colony formation capacity. Moreover, suppression of LINC00963 reduced the activity of stemness marker ALDH1, the percentage of self-renewal, chemoresistance and the expression of multidrug-resistance transporter ABCB5. Most importantly, we demonstrated that knockdown of LINC00963 decreased self-renewal, invasion and colony formation ability via ABCB5. Analysis of TCGA (the Cancer Genome Atlas) datasets suggested that the level of LINC00963 was positively correlated with the expression of the cancer stemness markers (Sox2 and CD44) and drug resistance markers (ABCG2 and ABCB5). Altogether, our results showed that suppression of LINC00963 may be beneficial to inhibit chemoresistance and cancer relapse in oral cancer patients.

• ABCB5
• LINC00963
• cancer stemness
• chemoresistance
• head and neck
• lncRNA

• ABC transporter druggability
• ABC transporters
• Cancer initiation
• Cancer progression
• Cancer stem cells
• Epithelial mesenchymal transition

• ATP-Binding Cassette Transporters/chemistry
• ATP-Binding Cassette Transporters/genetics
• ATP-Binding Cassette Transporters/metabolism
• Animals
• Biomarkers
• Cell Transformation, Neoplastic/genetics
• Cell Transformation, Neoplastic/metabolism
• Disease Progression
• Disease Susceptibility
• Drug Resistance, Neoplasm/genetics
• Epithelial-Mesenchymal Transition/genetics
• Gene Expression Regulation, Neoplastic
• Humans
• Neoplasms/drug therapy
• Neoplasms/etiology
• Neoplasms/metabolism
• Neoplasms/pathology
• Neoplastic Stem Cells/metabolism
• Signal Transduction
• Structure-Activity Relationship

• Cancer
• Cancer stem cells
• Chemoresistance
• Multidrug
• Therapy