• Circular RNAs
• Long non-coding RNAs
• Noncoding RNAs
• Pancreatic cancer
• Protein

• Humans
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• RNA, Untranslated/genetics
• RNA, Untranslated/metabolism
• Gene Expression Regulation, Neoplastic/genetics

• 5-fluorouracil
• Non-coding RNAs
• chemoresistance
• gastrointestinal cancers
• tumor microenvironment

• Epigenetic
• Flavonoids
• Nanoformulations
• Pancreatic cancer
• microRNA (miRNA)

• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Flavonoids/pharmacology
• Flavonoids/therapeutic use
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/metabolism
• Animals
• Gene Expression Regulation, Neoplastic/drug effects
• Signal Transduction/drug effects
• Cell Proliferation/drug effects
• Apoptosis/drug effects

• Invasion
• MIR600HG
• Migration
• PITPNM3
• Pancreatic cancer
• Proliferation
• miR-1197

• Cancer stem cells
• Pancreatic cancer
• Plasticity
• Stemness
• Tumor microenvironment

• 82173074 the National Natural Science Foundation of China
• No. 2022-PUMCH-D-001 the National High Level Hospital Clinical Research Funding
• No. 2022-PUMCH-B-004 the National High Level Hospital Clinical Research Funding
• No. 2021-I2M-1-002 the CAMS Innovation Fund for Medical Sciences
• 2018PT32014 the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences
• 3332022114 the Fundamental Research Funds for the Central Universities

• biomarker
• cancer
• diagnostics
• exosomes
• miRNA
• pancreatic cancer

• Humans
• MicroRNAs/metabolism
• DNA Copy Number Variations
• Carcinoma, Pancreatic Ductal/diagnosis
• Carcinoma, Pancreatic Ductal/genetics
• Carcinoma, Pancreatic Ductal/pathology
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• Biomarkers

Background: Increasing evidence suggested the critical roles of lncRNAs in the maintenance of genomic stability. However, the identification of genomic instability-related lncRNA signature (GILncSig) and its role in pancreatic cancer (PC) remains largely unexplored.

Methods: In the present study, a systematic analysis of lncRNA expression profiles and somatic mutation profiles was performed in PC patients from The Cancer Genome Atlas (TCGA). We then develop a risk score model to describe the characteristics of the model and verify its prediction accuracy. ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and CIBERSORT analysis were employed to reveal the correlation between tumor immune microenvironment, immune infiltration, immune checkpoint blockade (ICB) therapy, and GILncSig in PC.

Results: We identified 206 GILnc, of which five were screened to develop a prognostic GInLncSig model. Multivariate Cox regression analysis and stratified analysis revealed that the prognostic value of the GILncSig was independent of other clinical variables. Receiver operating characteristic (ROC) analysis suggested that GILncSig is better than the existing lncRNA-related signatures in predicting survival. Additionally, the prognostic performance of the GILncSig was also found to be favorable in patients carrying wild-type KRAS, TP53, and SMAD4. Besides, a nomogram exhibited appreciable reliability for clinical application in predicting the prognosis of patients. Finally, the relationship between the GInLncSig model and the immune landscape in PC reflected its application value in clinical immunotherapy.

Conclusion: In summary, the GILncSig identified by us may serve as novel prognostic biomarkers, and could have a crucial role in immunotherapy decisions for PC patients.

• Anticancer
• Cardenolides
• Cardiac glycosides
• Nerium oleander

• CERS6-AS1
• WIPI2
• miR-195-5p
• pancreatic cancer

• Apoptosis/genetics
• Cell Line, Tumor
• Cell Movement/genetics
• Cell Proliferation/genetics
• Gene Expression Regulation, Neoplastic
• Humans
• Membrane Proteins/genetics
• Membrane Proteins/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• Phosphatidylinositols
• RNA, Antisense
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Sphingosine N-Acyltransferase/genetics
• Sphingosine N-Acyltransferase/metabolism
• WD40 Repeats
• Pancreatic Neoplasms

Accumulating evidence indicates that abnormally expressed microRNAs (miRNAs, miRs) contribute to cancer progression. Nonetheless, the role of miR-30e-5p in pancreatic cancer (PCa) remains unclear. In this study, using quantitative real-time polymerase chain reaction analysis, we found that miR-30e-5p expression was downregulated in human PCa tissues compared with that in normal para-cancerous tissues. After transfecting with miR-30e-5p inhibitors, miR-30e-5p mimics, or empty vectors in the BxPC-3 and PANC-1 cells, respectively, the experiments revealed that the upregulation of miR-30e-5p expression inhibited cell growth, invasion, migration and epithelial-mesenchymal transition (EMT), and promoted apoptosis, while miR-30e-5p downregulation had the opposite effects. RNA sequencing of miR-30e-5p inhibitor-, miR-30e-5p mimic-, and the negative control (NC)-treated groups revealed that miR-30e-5p may affect epithelial cell differentiation, cell growth and death. Next, the snail family transcriptional repressor 1 (SNAI1) was predicted and verified as the target gene of miR-30e-5p using bioinformatics analysis and luciferase assays. SNAI1 expression levels were decreased in the PCa cells transfected with miR-30e-5p mimics, whereas the opposite was observed in the cells transfected with miR-30e-5p inhibitors. Subsequently, PCa cells were transfected with a vector overexpressing SNAI1 (OE-SNAI1) and miR-30e-5p mimics, miR-30e-5p inhibitors, or empty vectors. Compared with that in the OE-SNAI1 + miR-30e-5p NC group, transfection with OE-SNAI1 + miR-30e-5p mimics inhibited the PCa cell growth, migration, and increased apoptosis, whereas transfection with OE-SNAI1 + miR-30e-5p inhibitors had the opposite effects. In conclusion, miR-30e-5p potentially inhibits PCa cell proliferation, migration, and invasion via the SNAI1/EMT axis.

• EMT
• SNAI1
• miR-30e-5p
• pancreatic cancer

• Cancer
• Clinical biomarker
• Diagnosis
• Long non-coding RNA
• Prognosis

• 5.8S rRNA
• RNA sequencing
• RT-qPCR
• non-coding RNA
• small RNA

• 5' Untranslated Regions
• Animals
• Cell Line, Tumor
• Gene Expression Profiling
• Gene Expression Regulation
• Genetic Loci
• Humans
• Mice
• MicroRNAs/genetics
• RNA Transport
• RNA, Ribosomal/genetics
• RNA, Ribosomal, 5.8S/genetics
• RNA, Untranslated/genetics
• Ribonucleoproteins/genetics
• Transcriptome

• 289637 Fonds de recherche du Québec - Nature et technologies
• RGPIN-2019-06502 Natural Sciences and Engineering Research Council of Canada

Noncoding RNA (ncRNA) is involved in the occurrence, development, metastasis, and drug resistance of tumors and involves a variety of biological functions. In addition, miRNA can regulate proliferation and migration and even regulate epigenetics to promote the development of multiple myeloma (MM). However, the mechanism of ncRNA involved in MM is still unclear, and there are many unknown ncRNAs to be explored. This research is aimed at discovering the unknown lncRNA in MM through high-throughput sequencing and to study the mechanism and role of competitive endogenous RNA (ceRNA) involved in the pathogenesis of MM for the development of novel molecular markers and potential new targeted drugs. We screened out 262 new lncRNAs with statistical differences by RNA sequencing and selected the lncRNA MSTRG.29039.1 according to the expression and function of lncRNAs and their target genes in MM. We verified that MSTRG.29039.1 and its target gene OSMR were highly expressed in MM. After knockdown of MSTRG.29039.1 in MM cell lines, the expression of OSMR was decreased, and the expression of hsa-miR-12119 was upregulated which can also promote cell apoptosis and inhibit proliferation. Then, we knocked down hsa-miR-12119 and MSTRG.29039.1, we found that apoptosis of MM cells was reduced, and cell proliferation was increased compared with just knocking down hsa-miR-12119. We further verified the direct binding relationship between MSTRG.29039.1 and OSMR by the dual-luciferase reporter assay system. Thus, MSTRG.29039.1 can competitively bind with miRNA to counteract the inhibitory effect of miRNA on OSMR, which regulates cell proliferation and apoptosis through the JAK2/STAT3 pathway. In a conclusion, lncRNA MSTRG.29039.1 could promote proliferation by sponging hsa-miR-12119 via the JAK2/STAT3 pathway in multiple myeloma. This may be a molecular marker and a potential therapeutic target for MM.

Extreme hypoxia is among the most prominent pathogenic features of pancreatic cancer (PC). Both the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and hypoxic inducible factor-1α (HIF-1α) are highly expressed in PC patients and play a crucial role in disease progression. Reciprocal regulation involving PVT1 and HIF-1α in PC, however, is poorly understood. Here, we report that PVT1 binds to the HIF-1α promoter and activates its transcription. In addition, we found that PVT1 could bind to HIF-1α and increases HIF-1α post-translationally. Our findings suggest that the PVT1‒HIF-1α positive feedback loop is a potential therapeutic target in the treatment of PC.

• HIF-1α
• PVT1
• feedforward regulatory loop
• pancreatic cancer

• Circular RNA
• Long non-coding RNA
• MicroRNA
• Non-coding RNAs
• Pancreatic ductal adenocarcinoma

• angiogenesis
• circular RNAs
• gastrointestinal cancers
• long non-coding RNAs
• microRNAs
• non-coding RNAs

• PDAC
• biomarker
• diagnosis
• tRF-3
• tsRNAs

• Bladder cancer
• Chemoresistance
• LncRNA
• Metastasis
• MicroRNA
• Signal transducer and activator of transcription 3 (STAT3)

Gastric cancer (GC) is one of the most common types of malignant tumor and it demonstrates high mortality rates. The majority of cases of GC are diagnosed at an advanced stage, which seriously endangers the health of the patient. Therefore, discovering a novel diagnostic method for GC is a current priority. Exosomes are 40 to 150-nm-diameter vesicles consisting of a lipid bilayer secreted by a variety of cells that exist in multiple different types of body fluids. Exosomes contain diverse types of active substances, including RNAs, proteins and lipids, and play important roles in tumor cell communication, metastasis and neovascularization, as well as tumor growth. Non-coding RNAs (ncRNAs) do not code proteins, and instead have roles in a variety of genetic mechanisms, such as regulating the structure, expression and stability of RNAs, and modulating the translation and function of proteins. In recent years, exosomal ncRNAs have become a novel focus in research. An increasing number of studies have demonstrated that exosomal ncRNAs can be used in the prediction and treatment of GC. The present review briefly discusses the role of exosomal ncRNAs as a potential biomarker, and summarizes important regulatory genes involved in the development and progression of GC.

Pancreatic cancer (PC) is one of the most aggressive cancers and has an extremely poor prognosis worldwide. Long noncoding RNA (lncRNA) has been reported to be a potential prognostic biomarker in the initiation and prognosis of PC. Nevertheless, the biological functions and the detailed molecular mechanism of LINC00514 in PC remain unclear.

We measured the expression level of LINC00514 in PC tissues and cell lines by quantitative real-time PCR. Gain- and loss-of-function experiments were performed to explore the bioeffects of LINC00514 on PC development both in vitro and in vivo. Subcellular fractionation, luciferase reporter assay, RNA immunoprecipitation assay, pull-down assay and western blotting were performed to investigate the oncogenic molecular mechanisms of LINC00514.

In this study, LINC00514 was shown to be upregulated in PC tissues and cell lines. Increased LINC00514 expression was significantly associated with the clinical progression and prognosis of PC patients. In addition, silencing LINC00514 inhibited PC cell proliferation, migration and invasion, while LINC00514 overexpression promoted these processes. Moreover, LINC00514 knockdown remarkably inhibited PC development and metastasis in vivo. Deeper investigations indicated that LINC00514 acted as a sponge for microRNA-28-5p (miR-28-5p) in PC and that Rap1b was a downstream target of miR-28-5p. Furthermore, the positive correlation of LINC00514 and Rap1b and the negative correlation between miR-28-5p and LINC00514 (or Rap1b) were revealed. Based on the rescue assays, Rap1b inhibition partially suppressed the oncogenic effect of LINC00514 overexpression on PC cell proliferation, migration and invasion.

This study is the first to characterize the oncogenic function of the long noncoding RNA LINC00514 in pancreatic cancer progression by acting as a competing endogenous RNA (ceRNA) of miR-28-5p to upregulate Rap1b expression. Understanding this molecular mechanism might contribute to further discoveries of better diagnostic and therapeutic options for pancreatic cancer.

• Invasion
• LINC00514
• Pancreatic cancer
• Proliferation
• Rap1b
• miR-28-5p

• RNA sequence features
• deep neural networks
• noncoding RNA
• noncoding RNA prediction
• protein coding RNA

With increasing incidence, pancreatic cancer (PC) is one of the most common digestive tract tumors. However, the prognosis of PC is particularly dismal due to the highly invasive and metastatic behavior of this deadly disease. DEP domain-containing protein 1B (DEPDC1B), which is overexpressed in multiple tumors, such as breast cancer, oral cancer and non-small cell lung cancer, plays a significant role in cell movement, cell cycle and cytoskeleton reorganization. However, the function of DEPDC1B in PC remains poorly understood.

The function of DEPDC1B in the migration and invasion of PC was evaluated by wound healing and Transwell assays in vitro and PC-derived liver metastasis models in vivo. The molecular mechanisms of DEPDC1B were investigated through cell line establishment, Western blotting, qRT-PCR, immunoprecipitation, histological examination and immunohistochemistry analysis.

DEPDC1B was overexpressed in PC cell lines. DEPDC1B regulated cell migration and invasion. DEPDC1B regulated the Rac1/PAK1-LIMK1-cofilin1 signaling pathway by interacting with Rac1. Rac1 inhibition suppressed DEPDC1B-induced migration and invasion in PC in vitro and DEPDC1B-induced liver metastasis in vivo.

DEPDC1B promoted cell migration and invasion by activating the Rac1/PAK1-LIMK1-cofilin1 signaling pathway, thus providing a potential therapeutic target against PC.

• DEP domain-containing protein 1B
• Rac1/PAK1-LIMK1-cofilin1 signaling
• invasion
• migration
• pancreatic cancer

Long non-coding RNA (lncRNA) is abnormally expressed in various malignant tumors. In recent years, it has been found that IncRNA HULC is increasingly expressed in pancreatic cancer tissues and is involved in the development and progression of pancreatic cancer. However, the clinical value of serum HULC in pancreatic cancer remains unclear, and there are few studies on how HULC regulates the biological function of pancreatic cancer cells.

To determine the value of lncRNA HULC in the diagnosis and prognosis of pancreatic cancer, and its possible biological potential.

Sixty patients with pancreatic cancer and sixty patients with benign pancreatic diseases admitted to Xiangya Hospital, Central South University were assigned to the pancreatic cancer group and the benign disease group, respectively, and another 60 healthy subjects were enrolled as the normal group during the same period. HULC-siRNA and NC-siRNA were transfected into pancreatic cancer cells. Quantitative real-time polymerase chain reaction was performed to determine the expression of HULC in tissues, serum, and cells. Western Blot was carried out to determine the expression of β-catenin, c-myc, and cyclin D1 in cells, and the cell counting kit-8, flow cytometry, and Transwell assay were conducted to determine the proliferation, apoptosis and invasion of cells.

Highly expressed in the tissues and serum of pancreatic cancer patients, HULC showed good clinical value in distinguishing between patients with pancreatic cancer, patients with benign pancreatic diseases and healthy subjects. HULC was related to pathological parameters including tumor size, T staging, M staging and vascular invasion, and the area-under-the-curve for evaluating these four parameters was 0.844, 0.834, 0.928 and 0.818, respectively. Patients with low expression of HULC had a significantly higher 3-year overall survival (OS) and 5-year OS than those with high expression. T staging, M staging, vascular invasion, and HULC were independent prognostic factors affecting the 3-year OS of patients with pancreatic cancer. Inhibition of HULC expression prevented the proliferation and invasion of pancreatic cancer cells, promoted apoptosis, and inhibited the expression of Wnt/β-catenin signaling pathway-related proteins, β-catenin, c-myc, and cyclin D1. The Wnt/β-catenin signaling pathway agonist (LiCl) restored proliferation, apoptosis, and invasion of pancreatic cancer cells with inhibited expression of HULC.

HULC is an effective marker for the diagnosis and prognosis of pancreatic cancer, which may affect the biological function of pancreatic cancer cells through the Wnt/β-catenin signaling pathway.

• Long non-coding RNA HULC
• Diagnosis
• Prognosis
• Pancreatic cancer
• Wnt/β-catenin signaling pathway
• Biological function

• Biomarkers, Tumor/metabolism
• Case-Control Studies
• China/epidemiology
• Female
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/mortality
• Prognosis
• RNA, Long Noncoding/metabolism
• Wnt Signaling Pathway

• lncRNA
• overall survival
• pancreatic ductal adenocarcinoma
• prognosis
• signature

Genetic studies have advanced our understanding of pancreatic cancer at a mechanistic and translational level. Genetic concepts and tools are increasingly starting to be applied to clinical practice, in particular for precision medicine efforts. However, epigenomics is rapidly emerging as a promising conceptual and methodological paradigm for advancing the knowledge of this disease. More importantly, recent studies have uncovered potentially actionable pathways, which support the prediction that future trials for pancreatic cancer will involve the vigorous testing of epigenomic therapeutics. Thus, epigenomics promises to generate a significant amount of new knowledge of both biological and medical importance.

In pancreatic cancer, the epigenomic landscape can strongly impact the disease phenotype. Here, the authors discuss recent advances in our understanding of pancreatic cancer epigenomics, and how this knowledge can integrate with precision medicine approaches in this lethal disease.

Pancreatic cancer is a malignant disease that develops rapidly and carries a poor prognosis. Currently, surgery is the only radical treatment. Non-coding RNAs (ncRNAs) are protein-free RNAs produced by genome transcription; they play important roles in regulating gene expression, participating in epigenetic modification, cell proliferation, differentiation and reproduction. ncRNAs also play key roles in the development of cancer; microRNA (miRNA) and long non-coding RNA (lncRNA) may lead the way to new treatments for pancreatic cancer. miRNAs are short-chain ncRNAs (19–24 nt) that inhibit the degradation of protein translation or their target gene mRNAs to regulate gene expression. lncRNAs contain >200 nt of ncRNA and play important regulatory roles in a number of malignant tumors, in terms of tumor cell proliferation, apoptosis, invasion and distant metastasis. lncRNAs can be exploited for the diagnosis and treatment of pancreatic cancer and have substantial prospects for clinical application. Nevertheless, the molecular mechanism of their regulation and function, as well as the significance of other ncRNAs, such as piwi-interacting RNA, in the pathogenesis of pancreatic cancer, are largely unknown. In this review, the structures of ncRNAs with various classifications, as well as the functions and important roles of ncRNAs in the diagnosis and treatment of pancreatic cancer are reviewed.

• cancer
• diagnosis
• future therapeutics
• metastasis
• non-coding RNA
• treatment
• tumorigenesis

Long noncoding RNAs (lncRNAs) have been reported to be involved in a variety of human diseases, including cancers. However, their mechanisms have not yet been fully elucidated. We investigated lncRNA changes that may be associated with pancreatic cancer (PC) by analyzing published microarray data, and identified AGAP2-AS1 as a relatively overexpressed lncRNA in PC tissues. qRT-PCR assays were performed to examine expression levels of AGAP2-AS1. MTT assays, colony formation assays, and EdU assays were used to determine the proliferative capacity of cells. Flow cytometry and TUNEL assays were used to study the regulation of AGAP2-AS1 in the cell cycle and apoptosis. Transwell experiments were used to study changes in cell invasion and metastasis, and a nude mouse model was established to assess the effects of AGAP2-AS1 on tumorigenesis in vivo. RNA sequencing was performed to probe AGAP2-AS1-related pathways. Subcellular fractionation and FISH assays were used to determine the distribution of AGAP2-AS1 in PC cells, and RIP and ChIP were used to determine the molecular mechanism of AGAP2-AS1-mediated regulation of potential target genes. Increased expression of AGAP2-AS1 was associated with tumor size and pathological stage progression in patients with PC. RREB1 was found to activate transcription of AGAP2-AS1 in PC cells. AGAP2-AS1 affected proliferation, apoptosis, cycle arrest, invasion, and metastasis of PC cells in vitro, and AGAP2-AS1 regulated PC proliferation in vivo. Furthermore, AGAP2-AS1 epigenetically inhibited the expression of ANKRD1 and ANGPTL4 by recruiting zeste homolog 2 (EZH2), thereby promoting PC proliferation and metastasis. In summary, our data show that RREB1-induced upregulation of AGAP2-AS1 regulates cell proliferation and migration in PC partly through suppressing ANKRD1 and ANGPTL4 by recruiting EZH2. AGAP2-AS1 represents a potential target for the diagnosis and treatment of PC in the future.

• Long non-coding RNA
• pancreatic ductal adenocarcinoma
• pancreatic neuroendocrine tumors
• polymorphisms

• Adult
• Aged
• Alleles
• Case-Control Studies
• Cell Line, Tumor
• Female
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genotype
• Humans
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• Odds Ratio
• Pancreatic Neoplasms/genetics
• Polymorphism, Genetic
• RNA, Long Noncoding/genetics
• Risk Factors

• Antioxidant enzymes
• MicroRNA
• Microdissection
• Pancreatic cancer
• miRNA

• Colorectal carcinoma
• Esophageal squamous cell carcinoma
• Pancreatic ductal cell carcinoma
• Prognosis
• Tissue/serum microRNA-21

• Biomarkers, Tumor/metabolism
• Carcinoma, Pancreatic Ductal/blood
• Carcinoma, Pancreatic Ductal/mortality
• Circulating MicroRNA/metabolism
• Colorectal Neoplasms/blood
• Colorectal Neoplasms/mortality
• Esophageal Neoplasms/blood
• Esophageal Neoplasms/mortality
• Esophageal Neoplasms/pathology
• Esophageal Squamous Cell Carcinoma/blood
• Esophageal Squamous Cell Carcinoma/mortality
• Humans
• MicroRNAs/blood
• Pancreatic Neoplasms/blood
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/pathology
• Prognosis
• Survival Rate
• Pancreatic Neoplasms

• Adult
• Aged
• Biomarkers, Tumor/blood
• Carcinoma, Pancreatic Ductal/blood
• Carcinoma, Pancreatic Ductal/diagnosis
• Carcinoma, Pancreatic Ductal/mortality
• Carcinoma, Pancreatic Ductal/surgery
• Disease-Free Survival
• Early Detection of Cancer/methods
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Invasiveness/pathology
• Neoplasm Staging
• Pancreatectomy/methods
• Pancreatic Neoplasms/blood
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/surgery
• Prognosis
• Risk Assessment
• Survival Analysis

• Autophagy
• Long non-coding RNA
• PVT1
• Pancreatic ductal adenocarcinoma
• ULK1
• miR-20a-5p

• Animals
• Autophagy
• Autophagy-Related Protein-1 Homolog/genetics
• Autophagy-Related Protein-1 Homolog/metabolism
• Carcinoma, Pancreatic Ductal/genetics
• Carcinoma, Pancreatic Ductal/metabolism
• Carcinoma, Pancreatic Ductal/pathology
• Cell Line, Tumor
• Cell Proliferation
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Intracellular Signaling Peptides and Proteins/genetics
• Intracellular Signaling Peptides and Proteins/metabolism
• Male
• Mice
• MicroRNAs/genetics
• Neoplasm Transplantation
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology
• RNA, Long Noncoding/genetics

• the National Natural Science Foundation
• the Guangdong Province Natural Science Foundation
• the Science and Technology Planning Project of Guangdong Province
• the Foundation of the Guangzhou Science and Technology Bureau

Emerging evidence has identified that long non-coding RNAs (lncRNAs) may play an important role in the pathogenesis of many cancers, pancreatic cancer (PC) included. However, the role of linc00462 in PC remains unclear. The aim of our present study was to investigate the potential functions of linc00462 in PC and to identify the underlying mechanisms of action. CCK8 assay, transwell assay, cell cycle assay, cell apoptosis assay, EdU assay, western blot assay, cell adhesion assay, HE staining, IF staining, ELISA assay, vivo growth and metastasis assay, and colony formation assay were performed. We demonstrated that OSM mediated up-regulation of linc00462 promoted cell proliferation by accelerating cell cycle process and inhibiting cell apoptosis and adhesion in vitro, enhanced cell migration and invasion by accelerating EMT process, promoted tumor growth and matastasis in vivo and was associated with large tumor size, poor tumor differentiation, TNM stage and distant metastasis in patients of PC. In addition, we demonstrated that linc00462 was a target of miR-665. Linc00462 overexpression enhanced the expression levels of TGFBR1 and TGFBR2, and thus activated the SMAD2/3 pathway in PC cells. In conclusion, linc00462/miR-665/TGFBR1/2 regulatory network may shed light on tumorigenesis in PC.

• 3′ RACE
• Alternative splicing
• Cancer cell lines
• NGS
• SR-A1
• Splicing factors

• cancer stem cells
• cell biology

• Animals
• Carcinogenesis/genetics
• Carcinoma, Pancreatic Ductal/genetics
• Carcinoma, Pancreatic Ductal/pathology
• Cell Line, Tumor
• Datasets as Topic
• Disease Progression
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Introns/genetics
• Mice
• Mice, Nude
• MicroRNAs/antagonists & inhibitors
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Pancreas/pathology
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• RNA, Small Interfering/metabolism
• RNA-Binding Proteins/genetics
• RNA-Binding Proteins/metabolism
• Signal Transduction/genetics
• Transforming Growth Factor beta1/metabolism
• Up-Regulation
• Xenograft Model Antitumor Assays

• 23110 Cancer Research UK
• MR/L01632X/1 Medical Research Council
• NIHR-RP-011-053 Department of Health

• hepatocellular carcinoma
• long noncoding RNA
• microRNA
• piwi-interacting RNA
• small noncoding RNA
• therapy

• Noncoding RNA
• biomarker
• chemotherapy
• epigenetic regulation
• miRNAs
• pancreatic cancer.

• Antineoplastic Agents/pharmacology
• Biomarkers, Tumor/antagonists & inhibitors
• Biomarkers, Tumor/genetics
• Epigenesis, Genetic/drug effects
• Epigenesis, Genetic/genetics
• Humans
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/genetics
• RNA, Untranslated/antagonists & inhibitors
• RNA, Untranslated/genetics

• Adénocarcinome pancréatique
• Analyses à haut débit Génomique
• Classifications moléculaires
• Genomic
• High throughput analyses
• Metabolomic
• Molecular classification
• Métabolomique
• Pancreatic ductal adenocarcinoma
• Trancriptomique
• Transcriptomic

• endoscopic ultrasound-guided fine-needle aspiration
• molecular diagnostic
• molecular markers
• pancreatic ductal adenocarcinoma
• review

• Carcinoma, Pancreatic Ductal/diagnostic imaging
• Carcinoma, Pancreatic Ductal/genetics
• Carcinoma, Pancreatic Ductal/pathology
• Cyclin-Dependent Kinase Inhibitor p16
• Cyclin-Dependent Kinase Inhibitor p18/genetics
• Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods
• Endosonography/methods
• Female
• Humans
• Immunohistochemistry
• Male
• Molecular Diagnostic Techniques
• Neoplasm Invasiveness/pathology
• Neoplasm Staging
• Pancreatic Neoplasms/diagnostic imaging
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• Patient Care Team/organization & administration
• Sensitivity and Specificity
• Smad4 Protein/genetics

Clinical and pathologic markers of prognosis and patterns of failure help guide clinicians in selecting patients for adjuvant therapy after surgical resection for pancreatic adenocarcinoma (PDAC). Recent studies have reported the prognostic utility of microRNA profiling in numerous malignancies. Here, we review and summarize the current literature regarding associations between microRNA expression and overall survival in PDAC patients.

We conducted a systematic search in the PubMed database to identify all primary research studies reporting prognostic associations between tumor and/or serum microRNA expression and overall survival in PDAC patients. Eligible articles were reviewed by the authors and relevant findings are summarized below.

We found 53 publications that fit our search criteria. In total, 23 up-regulated and 49 down-regulated miRNAs have been associated with worse overall survival. MiR-21 is the most commonly reported miRNA, appearing in 19 publications, all of which report aberrant over-expression and association with shorter survival in PDAC. Other miRNAs that appear in multiple publications include miR-10b, −21, −34a, −155, −196a, −198, −200c, −203, −210, −218, −222, and −328. We summarize the preclinical and clinical data implicating these miRNAs in various molecular signaling pathways and cellular functions.

There is growing evidence that miRNA expression profiles have the potential to provide tumor-specific prognostic information to assist clinicians in more appropriately selecting patients for adjuvant therapy. These molecules are often aberrantly expressed and exhibit oncogenic and/or tumor suppressor functions in PDAC. Additional efforts to develop prognostic and predictive molecular signatures, and further elucidate miRNA mechanisms of action, are warranted.

• chemotherapy
• miRNA
• non-coding RNA
• pancreatic cancer
• prognostic biomarker