• Cholangiocarcinoma/genetics
• Cholangiocarcinoma/pathology
• Humans
• Tumor Microenvironment/genetics
• Epigenesis, Genetic
• Bile Duct Neoplasms/genetics
• Bile Duct Neoplasms/pathology
• Mutation
• Gene Expression Regulation, Neoplastic
• DNA Methylation/genetics

• ZIA BC010313 Intramural NIH HHS

• RNA-binding proteins
• biomarkers
• bone metastases
• cholangiocarcinoma
• extracellular vesicles
• hepatocellular carcinoma
• microRNAs
• therapy

• Humans
• MicroRNAs/metabolism
• MicroRNAs/genetics
• RNA-Binding Proteins/metabolism
• RNA-Binding Proteins/genetics
• Bone Neoplasms/secondary
• Bone Neoplasms/genetics
• Bone Neoplasms/metabolism
• Liver Neoplasms/genetics
• Liver Neoplasms/secondary
• Liver Neoplasms/pathology
• Liver Neoplasms/metabolism
• Gene Expression Regulation, Neoplastic
• Cholangiocarcinoma/genetics
• Cholangiocarcinoma/pathology
• Cholangiocarcinoma/metabolism
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/metabolism
• Animals

• Biomarker
• Cholangiocarcinoma
• Exosome
• Opisthorchis viverrini
• miRNA

• Cholangiocarcinoma/parasitology
• Cholangiocarcinoma/blood
• Cholangiocarcinoma/genetics
• Cholangiocarcinoma/diagnosis
• MicroRNAs/blood
• MicroRNAs/genetics
• Animals
• Exosomes/genetics
• Humans
• Opisthorchis/genetics
• Opisthorchiasis/complications
• Opisthorchiasis/parasitology
• Opisthorchiasis/blood
• Opisthorchiasis/diagnosis
• Bile Duct Neoplasms/parasitology
• Bile Duct Neoplasms/blood
• Bile Duct Neoplasms/genetics
• Bile Duct Neoplasms/diagnosis
• Biomarkers, Tumor/blood
• Biomarkers, Tumor/genetics
• Male
• Middle Aged
• Female
• High-Throughput Nucleotide Sequencing
• Gene Expression Profiling
• Computational Biology/methods
• Aged

• bladder
• cancer
• kidney
• miR-21
• prostate
• urinary system

• high‐precision
• microRNA therapy
• nanopipettes
• photoelectrochemical
• single cells

• Humans
• MicroRNAs
• HeLa Cells
• Feedback
• Precision Medicine

• 22034003 National Natural Science Foundation of China
• 21974059 National Natural Science Foundation of China
• 22174063 National Natural Science Foundation of China
• 21327902 National Natural Science Foundation of China
• ZYJH004 Excellent Research Program of Nanjing University

• ASOs
• Druggable targets
• Heart diseases
• Liver dysfunction
• MiRNAs
• ModRNAs
• RNA therapy
• aspirin (PubChem CID: 2244)
• bevasiranib (PubChem CID: 70695615)
• cobomarsen (PubChem CID: 126480232) anti miR-155
• fomivirsen (PubChem CID: 129651696)
• inclisiran (PubChem CID: 126480325)
• miR-122 (PubChem CID: 801592)
• neomycin (PubChem CID: 8378)
• patisiran (PubChem CID: 483928509)
• risdiplam (PubChem CID: 163321874)
• s-acetyl-cysteine (PubChem CID: 10130120)

• Humans
• MicroRNAs/genetics
• MicroRNAs/therapeutic use
• Non-alcoholic Fatty Liver Disease/drug therapy
• Non-alcoholic Fatty Liver Disease/genetics
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/genetics
• Metabolic Diseases/drug therapy
• Metabolic Diseases/genetics
• Heart Diseases
• Oligonucleotides, Antisense/therapeutic use

• Cholangiocarcinoma
• Circ RNA
• Drug resistance
• lncRNA
• miRNA
• ncRNA

• Biliary tract cancer
• Cholangiocarcinoma
• MicroRNAs
• Progression

• Biomarker
• Gallbladder cancer
• Liquid Biopsy
• MicroRNA
• Real time PCR

• Biomarkers
• Distal cholangiocarcinoma
• Intrahepatic cholangiocarcinoma
• Noncoding RNA
• Perihilar cholangiocarcinoma

Data from GLOBOCAN 2020 estimates that there were 19.3 million new cases of cancer and 10.0 million cancer-related deaths in 2020 and that this is predicted to increase by 47% in 2040. The combined burden of cancers of the gastrointestinal (GI) tract, including oesophageal-, gastric- and colorectal cancers, resulted in 22.6% of the cancer-related deaths in 2020 and 18.7% of new diagnosed cases. Understanding the aetiology of GI tract cancers should have a major impact on future therapies and lessen this substantial burden of disease. Many cancers of the GI tract have suppression of the tumour suppressor Programmed Cell Death 4 (PDCD4) and this has been linked to the expression of microRNAs which bind to the untranslated region of PDCD4 mRNA and either inhibit translation or target the mRNA for degradation. This review highlights the properties of PDCD4 and documents the evidence for the regulation of PDCD4 expression by microRNAs in cancers of the GI tract.

There have been a variety of published studies on the expression of serum miR-21 in patients with ovarian cancer associated with the diagnostic value of ovarian cancer, but the conclusions are not clearly elucidated. This study aims to evaluate the value of serum miR-21 expression in the diagnosis of patients with ovarian cancer by meta-analysis.

Databases, such as PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and China WanFang, were searched for relevant studies upon the correlation between the expression of serum miR-21 and the diagnostic value of ovarian cancer from inception to March 7, 2022. Statistical analysis was performed using Stata 15.0 software. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated. The meta-regression analysis and subgroup analysis were used to explore the sources of heterogeneity. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) system was used to evaluate the quality of the included literature.

A total of 6 articles were included in the meta-analysis. The results showed that the pooled sensitivity, specificity, PLR, NLR, and DOR were 0.81 (95%CI: 0.73–0.88), 0.82 (95%CI: 0.75–0.87), 4.51 (95%CI: 3.22–6.31), 0.23 (95%CI: 0.16–0.33), and 19.87 (95% CI: 11.27–35.03), respectively. The area under the summary receiver operating characteristic curve was 0.89 (95%CI: 0.85–0.91). No significant publication bias was found (P > 0.05).

Serum miR-21 has a good diagnostic value for ovarian cancer, which can be an ideal diagnostic biomarker for ovarian cancer. However, we should gingerly use miR-21 as a diagnostic reference standard, due to the limited number of included studies and heterogeneity.

• Cholangiocarcinoma
• Hippo pathway
• Suberoylanilide hydroxamic acid
• YAP/TAZ

Cholangiocarcinoma is an uncommon and highly aggressive biliary tract malignancy with few manifestations until late disease stages. Diagnosis is currently achieved through a combination of clinical, biochemical, radiological and histological techniques. A number of reported cancer biomarkers have the potential to be incorporated into diagnostic pathways, but all lack sufficient sensitivity and specificity limiting their possible use in screening and early diagnosis. The limitations of standard serum markers such as CA19-9, CA125 and CEA have driven researchers to identify multiple novel biomarkers, yet their clinical translation has been slow with a general requirement for further validation in larger patient cohorts. We review recent advances in the diagnostic pathway for suspected CCA as well as emerging diagnostic biomarkers for early detection, with a particular focus on non-invasive approaches.

• ERCP (Endoscopic Retrograde Cholangiopancreatography)
• biliary strictures
• biomarkers
• cholangiocarcinoma
• early detection
• primary sclerosing cholangitis (PSC)

• HCC
• PTEN
• fibrosis
• immune cells
• inflammation
• microRNA 21
• oncogenes
• tumor suppressors

• 310030-172862 Swiss National Science Foundation
• 320030-20030 Swiss National Science Foundation
• CRSII3-160717 Swiss National Foundation

In this pilot study, using next-generation sequencing and integrated messenger RNA (mRNA) sequencing, we investigated circulating microRNA (miRNA) expression profiling from bile-derived exosomes to identify dysregulated miRNA signatures and oncogenic pathways and determine their effects on targeted mRNAs in cholangiocarcinoma (CCA). Moreover, we explored the possibility that genetic analysis using bile-derived exosomes may replace gene analysis using tissue.

Bile was collected from a patient with perihilar CCA before curative resection. As a control, bile was collected from a patient with a common bile duct stone. Exosomes were isolated from the bile, and we performed next-generation miRNA sequencing using isolated exosomes. To evaluate miRNA-mRNA interactions, mRNA sequencing was performed using bile fluid in both patients.

We identified 22 differentially expressed miRNAs. More than 65% of the predicted mRNA targets of those miRNAs were actually differentially expressed between control and CCA bile samples. In functional pathway analysis, targets of 22 miRNAs were primarily enriched in mitogen-activated protein kinase, platelet derived growth factor, vascular endothelial growth factor, epidermal growth factor receptor, and p53 signaling. In particular, in the functional assessment of miRNA-mRNA interactions, RAS pathways, including downstream pathways (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), were determined to be enriched.

Circulating miRNAs in bile-derived exosomes provide new information for the development of miRNA analysis in CCA. These miRNAs may represent the oncogenic characteristics of CCA tissue, enabling them to be used instead of tissue samples for the diagnosis of CCA. Further research investigating circulating miRNAs in bile exosomes may lead to more rational, targeted approaches to treatment.

• Bile
• Exosomes
• MicroRNAs
• Tumor microenvironment

Cholangiocarcinoma (CCA), an aggressive malignancy, is typically diagnosed at an advanced stage. It is associated with dismal 5-year postoperative survival rates, generating an urgent need for prognostic and diagnostic biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are associated with cancer regulation, including modulation of cell cycle progression, apoptosis, metastasis, angiogenesis, autophagy, therapy resistance, and epithelial–mesenchymal transition. Several miRNAs have been found to be dysregulated in CCA and are associated with CCA-related risk factors. Accumulating studies have indicated that the expression of altered miRNAs could act as oncogenic or suppressor miRNAs in the development and progression of CCA and contribute to clinical diagnosis and prognosis prediction as potential biomarkers. Furthermore, miRNAs and their target genes also contribute to targeted therapy development and aid in the determination of drug resistance mechanisms. This review aims to summarize the roles of miRNAs in the pathogenesis of CCA, their potential use as biomarkers of diagnosis and prognosis, and their utilization as novel therapeutic targets in CCA.

• cholangiocarcinoma
• diagnostic biomarker
• microRNA
• prognostic biomarker

• cancer
• fatty liver
• fibrosis
• hepatitis

Objectives: Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant cancer. More than 70% of patients are diagnosed at an advanced stage. The aim of this study was to evaluate the diagnostic value of plasma miR-21, miR-122, and CA19-9, hoping to establish a novel model to improve the accuracy for diagnosing iCCA. Materials and methods: Plasma miR-21 and miR-122 were detected in 359 iCCA patients and 642 controls (healthy, benign liver lesions, other malignant liver tumors). All 1001 samples were allocated to training cohort (n = 668) and validation cohort (n = 333) in a chronological order. A logistic regression model was applied to combine these markers. Area under the receiver operating characteristic curve (AUC) was used as an accuracy index to evaluate the diagnostic performance. Results: Plasma miR-21 and miR-122 were significantly higher in iCCA patients than those in controls. Higher plasma miR-21 level was significantly correlated with larger tumor size (p = 0.030). A three-marker model was constructed by using miR-21, miR-122 and CA19-9, which showed an AUC of 0.853 (95% CI: 0.824–0.879; sensitivity: 73.0%, specificity: 87.4%) to differentiate iCCA from controls. These results were subsequently confirmed in the validation cohort with an AUC of 0.866 (0.825–0.901). The results were similar for diagnosing early (stages 0–I) iCCA patients (AUC: 0.848) and CA19-9^negative iCCA patients (AUC: 0.795). Conclusions: We established a novel three-marker model with a high accuracy based on a large number of participants to differentiate iCCA from controls. This model showed a great clinical value especially for the diagnosis of early iCCA and CA19-9^negative iCCA.

• CA19-9
• circulating biomarker
• diagnosis
• intrahepatic cholangiocarcinoma
• microRNA

The Notch family includes evolutionary conserved genes that encode for single-pass transmembrane receptors involved in stem cell maintenance, development and cell fate determination of many cell lineages. Upon activation by different ligands, and depending on the cell type, Notch signaling plays pleomorphic roles in hepatocellular carcinoma (HCC) affecting neoplastic growth, invasion capability and stem like properties. A specific knowledge of the deregulated expression of each Notch receptor and ligand, coupled with resultant phenotypic changes, is still lacking in HCC. Therefore, while interfering with Notch signaling might represent a promising therapeutic approach, the complexity of Notch/ligands interactions and the variable consequences of their modulations raises concerns when performed in undefined molecular background. The gamma-secretase inhibitors (GSIs), representing the most utilized approach for Notch inhibition in clinical trials, are characterized by important adverse effects due to the non-specific nature of GSIs themselves and to the lack of molecular criteria guiding patient selection. In this review, we briefly summarize the mechanisms involved in Notch pathway activation in HCC supporting the development of alternatives to the γ-secretase pan-inhibitor for HCC therapy.

• Hepatocellular carcinoma
• NOTCH
• cancer therapy
• ncRNAs

• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Hepatitis Viruses
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• RNA, Untranslated/genetics
• Receptors, Notch/genetics
• Signal Transduction

Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous primary liver cancer, and currently there exist only a few options of targeted therapy. Histopathologically, iCCA is sub-classified according to morphology (mass forming type, periductal infiltrating type, and intraductal growing type) and histology (small duct type and large duct type). According to different histopathological types, clinical features such as risk factors and prognosis vary. Recent developments in genomic profiling have revealed several molecular markers for poor prognosis and activation of oncogenic pathways. Exploration of molecular characteristics of iCCA in each patient is a major challenge in a clinical setting, and there is no effective molecular-based targeted therapy. However, several recent studies suggested molecular-based subtypes with corresponding clinical and pathological features. Even though the subtypes have not yet been validated, it is possible that molecular features can be predicted based on clinicopathological characteristics and that this could be used for a more rational approach to integrative clinical and molecular subclassification and targeted therapy. In this review, we explored the genomic landscape of iCCA and attempted to find relevance between clinicopathologic and molecular features in molecular subtypes in several published studies. The results reveal future directions that may lead to a rational approach to the targeted therapy.

• Cholangiocarcinoma
• Mutation
• Gene expression
• Pathway
• Target therapy
• Molecular

• LncRNA
• biliary tract cancer
• biomarker
• miRNA
• non-coding RNA
• therapy

• MAPK
• lipopolysaccharide
• liver
• methionine selenium
• microRNA-155
• necroptosis
• oxidative stress

• SERS
• corrugated nanopillars
• high-aspect-ratio nanostructures
• miRNA detection
• nanobiosensor

• Biosensing Techniques
• Colorectal Neoplasms/diagnosis
• Gold
• Humans
• Limit of Detection
• Metal Nanoparticles
• MicroRNAs
• Silicon
• Spectrum Analysis, Raman
• Surface Properties

• VGHUST107-G6-1-1, VGHUST105-G6-1-1 Veterans General Hospitals and University System of Taiwan Joint Research Program
• 106-2923-E-007-004-MY3, 107-2221-E-007-012-MY3, 107-2622-E-007-006-CC2, 108-3017-F-007-0032 Ministry of Science and Technology (MOST), Taiwan
• MOE 107QR001I5 Ministry of Education, Taiwan

• Antineoplastic Agents/pharmacology
• Biliary Tract Neoplasms/drug therapy
• Biliary Tract Neoplasms/metabolism
• Biliary Tract Neoplasms/pathology
• CRISPR-Cas Systems
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Cell Survival/drug effects
• Cholangiocarcinoma/drug therapy
• Cholangiocarcinoma/metabolism
• Cholangiocarcinoma/pathology
• Cisplatin/pharmacology
• Deoxycytidine/analogs & derivatives
• Deoxycytidine/pharmacology
• Drug Discovery
• Drug Resistance, Neoplasm/genetics
• Gene Expression Regulation, Neoplastic
• High-Throughput Screening Assays/methods
• Humans
• MicroRNAs/antagonists & inhibitors
• MicroRNAs/metabolism
• Xenograft Model Antitumor Assays
• Gemcitabine

• 22897 Cancer Research UK
• 18052 Cancer Research UK
• CRUK FUNDED CANCER THERAPEUTICS UNIT AT ICR Cancer Research UK
• BRC to ICR/Marsden Department of Health
• CDF TO NV Cancer Research UK
• PW is a CRUK Life Fellow Cancer Research UK
• Pancreatic Cancer Action
• Pancreatic Cancer UK
• Associazione Italiana per la Ricerca sul Cancro
• National Institute for Health Research (NIHR)
• University of Glasgow
• Cancer Research UK
• European Commission

Previously, we developed a monoclonal antibody (mAb) NJ001 that binds to the antigen SP70 in human non‐small cell lung cancer (NSCLC) cells and showed it could inhibit lung adenocarcinoma (AD) growth. Here, we investigated the effect and mechanisms of NJ001 in lung AD metastasis.

Human lung AD cells (SPC‐A1 and A549) were treated with different concentrations of mAb NJ001, and the effects of NJ001 on cell migration and invasive activity were investigated using wound‐healing and Matrigel assays, respectively. The molecular mechanism of this inhibition was explored by microarrays, qRT‐PCR, western blot, luciferase assays and electrophoretic mobility shift assays (EMSA).

MAb NJ001 markedly suppressed lung AD cell migration; and the invasiveness of SPC‐A1 and A549 cells treated with mAb NJ001 was diminished by 65%. Tissue inhibitor of matrix metalloproteinase‐3 (TIMP‐3) was highly expressed in SPC‐A1 cells treated with mAb NJ001, whereas knockdown of TIMP‐3 by shRNA significantly increased SPC‐A1 and A549 invasiveness. MAb NJ001 affects lung AD by inhibiting TIMP‐3 through direct transcriptional regulation of FOXP1 binding sites in the TIMP‐3 promoter region, as shown in luciferase assays and EMSA.

MAb NJ001 inhibits invasiveness and metastasis in lung AD through the FOXP1 binding sites in the TIMP‐3 promoter region. It may have clinical applications in preventing and treating metastatic lung AD.

• Invasiveness
• SP70 antigen
• mAb NJ001
• non-small cell lung cancer
• tissue inhibitor of metalloproteinase-3

Galangin, a natural flavonoid product derived from the root of galangal, is emerging as a promising anticancer agent against multiple cancers. Yet, whether it also has antitumor effects on cholangiocarcinoma (CCA) and the underlying mechanism is still unknown. Herein, we demonstrate that galangin exhibits multiple antitumor effects on CCA cells including decreases cell viability; inhibits proliferation, migration, and invasion; and induces apoptosis. Moreover, those phenotypic changes are associated with downregulated microRNA-21 (miR-21) expression. To support, overexpression of miR-21 blocks galangin-mediated antisurvival and metastasis effects on CCA cells. Mechanically, galangin increases the expression of phosphatase and tensin homolog (PTEN), a direct target of miR-21, resulting in decreased phosphorylation of AKT, a protein kinase which plays a critical role in controlling survival and apoptosis. In contrast, overexpression of miR-21 abrogates galangin-regulated PTEN expression and AKT phosphorylation. Taken together, these findings indicate that galangin inhibits CCA cell proliferation and metastasis and induces cell apoptosis through a miR-21-dependent manner, and galangin may provide a novel potential therapeutic adjuvant to treat CCA.

• cholangiocarcinoma
• noncoding RNAs
• cancer
• tumourigenesis
• metastasis
• mechanism
• future therapeutics

Cholangiocarcinoma (CCA), an aggressive tumor with poor prognosis, is a malignant cancer with increasing incidence and mortality rates. It is important to survey crucial genes in CCA to find and design potential drug targets, especially for those genes associated with cell proliferation that is a key biological process in tumorgenesis. Herein, we surveyed genes associated with cell proliferation via a comprehensive pan-cancer analysis. Candidate genes were further analyzed using multiple approaches, including cross-analysis from diverse molecular levels, examination of potential function and interactions, and additional experimental validation. We primarily screened 15 potential genes based on 11 validated genes, and these 26 genes were further examined to delineate their biological functions and potential roles in cancer treatment. Several of them were involved synthetically lethal genetic interactions, especially for RECQL4, TOP2A, MKI67 and ASPM, indicating their potential roles in drug design and cancer treatment. Further experimental validation indicated that some genes were significantly upregulated in several cancer cell lines, implying their important roles in tumorigenesis. Our study identifies some genes associated with cell proliferation, which may be potential future targets in molecular targeted therapy.

• cell proliferation
• cholangiocarcinoma (CCA)
• synthetic lethality
• therapeutic target

• Cholangiocarcinoma
• Collagen type III, COL3A1
• Desmoplastic stroma
• Matrisome

MicroRNAs are known to play essential role in the gene expression regulation in cancer. In our research, next-generation sequencing technology was applied to explore the abnormal miRNA expression of oral squamous cell carcinoma (OSCC) in Chinese hamster. A total of 3 novel miRNAs (Novel-117, Novel-118, and Novel-135) and 11 known miRNAs (crg-miR-130b-3p, crg-miR-142-5p, crg-miR-21-3p, crg-miR-21-5p, crg-miR-542-3p, crg-miR-486-3p, crg-miR-499-5p, crg-miR-504, crg-miR-34c-5p, crg-miR-34b-5p and crg-miR-34c-3p) were identified. We conducted functional analysis, finding that 340 biological processes, 47 cell components, 46 molecular functions were associated with OSCC. Meanwhile the gene expression of Caspase-9, Caspase-3, Bax, and Bcl-2 were determined by qRT-PCR and the protein expression of PTEN and p-AKT by immunohistochemistry. Our research proposed further insights to the profiles of these miRNAs and provided a basis for investigating the regulatory mechanisms involved in oral cancer research.

• Exosome
• ICP
• biomarkers
• miR-21
• miR-29a
• miR-590-3p
• urine

the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin. Consequently, preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular, histological and pathophysiological features. Intraepithelial neoplasms are reported in biliary tract, as biliary intraepithelial neoplasm (BilIN), and in pancreas, as pancreatic intraepithelial neoplasm (PanIN). Both can evolve to invasive carcinomas, respectively cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary neoplasms arise in biliary tract and pancreas. Intraductal papillary neoplasm of the biliary tract (IPNB) share common histologic and phenotypic features such as pancreatobiliary, gastric, intestinal and oncocytic types, and biological behavior with the pancreatic counterpart, the intraductal papillary mucinous neoplasm of the pancreas (IPMN). All these neoplastic lesions exhibit similar immunohistochemical phenotypes, suggesting a common carcinogenic process. Indeed, CCA and PDAC display similar clinic-pathological features as growth pattern, poor response to conventional chemotherapy and radiotherapy and, as a consequence, an unfavorable prognosis. The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells.

• Biliary
• Pancreatic
• Progenitors
• Preneoplastic
• Common
• Tumor

• Bile Duct Neoplasms/etiology
• Bile Duct Neoplasms/pathology
• Bile Duct Neoplasms/therapy
• Biliary Tract/pathology
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/metabolism
• Carcinogenesis/pathology
• Carcinoma in Situ/etiology
• Carcinoma in Situ/pathology
• Carcinoma in Situ/therapy
• Carcinoma, Pancreatic Ductal/etiology
• Carcinoma, Pancreatic Ductal/pathology
• Carcinoma, Pancreatic Ductal/therapy
• Cholangiocarcinoma/etiology
• Cholangiocarcinoma/pathology
• Cholangiocarcinoma/therapy
• Disease Progression
• Humans
• Pancreas/pathology
• Pancreatic Neoplasms/etiology
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/therapy
• Precancerous Conditions/etiology
• Precancerous Conditions/pathology
• Precancerous Conditions/therapy
• Stem Cells/pathology

Tissue inhibitor of metalloproteinase-3 (TIMP-3), a secreted glycoprotein, plays an important role in carcinogenesis. It can bind to many proteinases to suppress their activity and thus protect the extracellular matrix from degradation. TIMP-3 may have many anticancer properties, including apoptosis induction and antiproliferative, antiangiogenic, and antimetastatic activities. This review summarizes the structure, proteinase inhibition ability, genetic and epigenetic regulation, cancer therapy potential, and contribution to cancer development of TIMP-3. Furthermore, in this review we discuss its potential as a biomarker for predicting cancer progression and the current state of drugs that target TIMP-3, either alone or in combination with clinical treatment. In conclusion, TIMP-3 can be a biomarker of cancer and a potential target for cancer therapy. This review article can serve as a basis to understand how to modulate TIMP-3 levels as a drug target of cancers.

• cancer therapy
• extracellular matrix
• matrix metalloproteinase
• metastasis
• tissue inhibitors of metalloproteinases-3

• MCRS1
• Wnt
• hepatocellular carcinoma
• invasion
• miR-186
• migration
• proliferation

Glioma is the most common malignant tumor of the central nervous system with high morbidity and mortality. Circular RNAs (circRNAs) are abundant non-coding RNAs, which contribute to tumor progression by competing with other endogenous RNAs such as microRNA (miRNA). MiRNA are a class of small non-coding RNAs, which interrupt the translation of target mRNAs. CircPCMTD1 (hsa-circ-0001801) is a newly discovered circRNA that was found to be significantly upregulated in glioma. However, its function is unclear. In this study, circPCMTD1 upregulation promoted the cell viability, migration and invasion dramatically, while the inhibition of circPCMTD1 led to a significant reduction of tumor growth in vivo. MiRNAs microarray analyses on circPCMTD1 silencing models in U251 and U118MG cells were performed, and the results suggested that circPCMTD1 knockdown could upregulate the expression of miR-224-5p and downregulate the expression of mTOR, one of miR-224-5p targets, in both cell lines. According to the prediction from circular RNA interactome and Targetscan, there was a complementary sequence in circPCMTD1 for miR-224-5p. Dual-luciferase reporter assay demonstrated that circPCMTD1 were targets of miR-224-5p. RIP assay was also performed to further confirm their directly interaction. Overexpression of miR-224-5p inhibited the viability and proliferation, migration, and invasion of U251 and U118MG glioma cells. In conclusion, circPCMTD1 could contribute to the promotion of glioma progression, and it may serve as the sponge of miR-224-5p to exert its function.

• U118MG cells
• U251 cells
• circPCMTD1
• glioma
• miR-224-5p
• oncogene

• Pleiotropic effects
• Pulmonary remodeling
• Target regulation
• microRNA-21

• cholangiocarcinoma
• metastasis
• precision therapy

• CCA prognosis
• biliary cancer
• biomarker
• early diagnosis
• omics

• Biomarkers, Tumor/genetics
• Carcinogenesis/genetics
• DNA Methylation/genetics
• Epigenesis, Genetic
• Gene Expression Regulation, Neoplastic
• Humans
• Medical Oncology/trends
• MicroRNAs/genetics
• Neoplasms/genetics
• Neoplasms/pathology
• Prognosis

• International Center for Genetic Engineering and Biotechnology