• Diagnosis
• Liposarcoma
• Prognosis
• lncRNAs
• miRNAs
• ncRNAs

• FBXO11
• Gastric cancer (GC)
• mammalian target of rapamycin pathway (mTOR pathway)
• miR-155-5p
• proliferation

• driver genes
• liposarcoma
• molecular pathogenesis
• outlook
• targeted therapy

• Natural Science Foundation of Shandong Province

• biomarkers
• miRNA
• rhabdomyosarcoma
• sarcoma
• soft tissue sarcoma
• tumorigenesis

• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Sarcoma/genetics
• Sarcoma/pathology
• Gene Expression Regulation, Neoplastic
• Animals

• DNA methylation
• Sarcomas
• biomarkers
• liquid biopsy
• next-generation sequencing

• Adult
• Humans
• Sarcoma/diagnosis
• Sarcoma/genetics
• Sarcoma/pathology
• Soft Tissue Neoplasms/diagnosis
• Soft Tissue Neoplasms/genetics
• Soft Tissue Neoplasms/pathology
• Liquid Biopsy
• High-Throughput Nucleotide Sequencing/methods
• Biomarkers

• dedifferentiated liposarcoma
• epigenetic changes
• liposarcoma
• molecular genetic abnormalities
• myxoid pleomorphic liposarcoma
• myxoid/round-cell liposarcoma
• pleomorphic liposarcoma
• targeted therapy
• well-differentiated liposarcoma

• 23-65-00003 Russian Science Foundation

• biomarkers
• bladder cancer
• microRNAs
• prostate cancer
• renal cancer
• upper tract urothelial carcinoma
• urological cancers

• Humans
• RNA, Small Untranslated/genetics
• Lipopolysaccharides
• Sarcoma/genetics
• Biomarkers
• RNA, Transfer
• Carcinogenesis

• P30 CA016058 NCI NIH HHS
• R21 CA263137 NCI NIH HHS
• U54 CA168512 NCI NIH HHS

• microRNA
• predictive biomarkers
• prognostic biomarkers
• soft tissue sarcomas
• treatment resistance

• chemotherapy
• genetic variants
• lung adenocarcinoma
• miRNA target sites
• response
• survival

• Singapore Ministry of Education
• National University of Singapore
• Singapore MOE AcRF Tier 2
• Yong Loo Lin School of Medicine, National University of Singapore

Currently, the search for new promising tools of immunotherapy continues. In this regard, microRNAs (miRNAs) that influence immune checkpoint (IC) gene expression in tumor and T-cells and may be important regulators of immune cells are considered. MiRNAs regulate gene expression by blocking mRNA translation. An important feature of miRNA is its ability to affect the expression of several genes simultaneously, which corresponds to the trend toward the use of combination therapy. The article provides a list of miRNAs acting simultaneously on several ICs and miRNAs that, in addition to IC, can regulate the expression of targeted therapy genes. There is dependence of miRNA interactions with IC genes on the type of cancer. The analysis of the accumulated data demonstrates that only about 14% (95% CI: 9.8–20.1%) of the studied miRNAs regulate the expression of specific IC in more than one type of cancer. That is, there is tumor specificity in the miRNA action on ICs. A number of miRNAs demonstrated high efficiency in vitro and in vivo. This indicates the potential of miRNAs as promising agents for cancer immunotherapy. Additional studies of the miRNA–gene interaction features and the search for an optimal miRNA mimic structure are necessary.

• dedifferentiated liposarcoma
• lipoma
• microRNA
• undifferentiated pleomorphic sarcoma
• well-differentiated liposarcoma

• extracellular vesicles
• fallopian tube
• miR-320a-3p
• microRNA
• oocytes

• FTO
• Renal cell carcinoma
• m(6)A
• miR-155

• aldosterone
• casein kinase 1
• mineralocorticoid receptor
• phosphorylation, cardiovascular diseases, aging
• posttranslational modification

• Wnt signaling
• YAP
• cancer
• epigenetics
• therapeutics
• β-catenin

Soft tissue sarcoma is a rare mesenchymal malignancy. Despite the advancements in the fields of radiology, pathology and surgery, these tumors often recur locally and/or with metastatic disease. STS is considered to be a diagnostic challenge due to the large variety of histological subtypes with clinical and histopathological characteristics which are not always distinct. One of the important clinical problems is a lack of useful biomarkers. Therefore, the discovery of biomarkers that can be used to detect tumors or predict tumor response to chemotherapy or radiotherapy could help clinicians provide more effective clinical management.

Soft tissue sarcomas (STSs) are a heterogeneous group of rare tumors. Although constituting only 1% of all human malignancies, STSs represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. Over 100 histologic subtypes have been characterized to date (occurring predominantly in the trunk, extremity, and retroperitoneum), and many more are being discovered due to molecular profiling. STS mortality remains high, despite adjuvant chemotherapy. New prognostic stratification markers are needed to help identify patients at risk of recurrence and possibly apply more intensive or novel treatments. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the most relevant cellular, molecular and metabolic biomarkers for STS, and highlight advances in STS-related biomarker research.

• immune checkpoints
• lncRNA
• metabolite
• oncogene
• prognostic/predictive biomarker
• soft tissue sarcoma

• Cancer
• Immune checkpoint
• Immunotherapy
• Inhibitory receptor

• Cell signalling
• Dedifferentiated liposarcoma
• Genomic mutation
• MDM2 amplification
• Well-differentiated liposarcoma

Soft tissue sarcoma (STS) is a heterogeneous group of rare malignancies with a five-year survival rate of approximately 50%. Reliable molecular markers for risk stratification and subsequent therapy management are still needed. Therefore, we analyzed the prognostic potential of miR-155-5p and miR-203a-3p expression in a cohort of 79 STS patients. MiR-155-5p and miR-203a-3p expression was measured from tumor total RNA by qPCR and correlated with the demographic, clinicopathological, and prognostic data of the patients. Elevated miR-155-5p expression was significantly associated with increased tumor stage and hypoxia-associated mRNA/protein expression. High miR-155-5p expression and low miR-203a-3p expression, as well as a combination of high miR-155-5p and low miR-203a-3p expression, were significantly associated with poor disease-specific survival in STS patients in the Kaplan–Meier survival analyses (p = 0.027, p = 0.001 and p = 0.0003, respectively) and in the univariate Cox regression analyses (RR = 1.96; p = 0.031; RR = 2.59; p = 0.002 and RR = 4.76; p = 0.001, respectively), but not in the multivariate Cox regression analyses. In conclusion, the oncomiR miR-155-5p and the tumor suppressor-miR miR-203a-3p exhibit an association with STS patient prognosis and are suggested as candidates for risk assessment.

• miR-155-5p
• miR-203a-3p
• prognosis
• soft tissue sarcoma

• Cell proliferation
• Hepatocellular carcinoma
• Invasion
• Migration
• PEG-IFN
• Wnt pathway
• miR-155

• Adult
• Aged
• Cluster Analysis
• DNA Methylation/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Genetic Heterogeneity
• Humans
• Liposarcoma/genetics
• Male
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Middle Aged
• Neoplasm Recurrence, Local/genetics
• Principal Component Analysis

• biomarkers
• epigenetics
• in-stent restenosis
• microRNAs
• personalized and precision medicine

Liposarcoma is a malignant tumor of mesenchymal origin with significant tissue diversity. It is composed of adipocytes with different degrees of differentiation and different degrees of heteromorphosis. It is not sensitive to traditional radiotherapy and chemotherapy and has a poor prognosis. In recent years, with the rapid development of basic immunology, molecular genetics and tumor molecular biology, the histological classification of liposarcoma has become increasingly clear. More and more new methods and technologies, such as gene expression profile analysis, the whole genome sequencing, miRNA expression profile analysis and RNA sequencing, have been successfully applied to liposarcoma, bringing about a deeper understanding of gene expression changes and molecular pathogenic mechanisms in the occurrence and development of liposarcoma. This study reviews the present research status and progress of cellular and molecular alterations of liposarcoma and corresponding clinical treatment progress.

• Clinical Treatment
• Cytogenetics
• Epigenetics
• Liposarcoma
• Molecular genetics

Approximately 30–50% of malignant growths can be prevented by avoiding risk factors and implementing evidence-based strategies. Colorectal cancer (CRC) accounted for the second most common cancer and the third most common cause of cancer death worldwide. This cancer subtype can be reduced by early detection and patients’ management. In this study, the functional roles of the identified microRNAs were determined using an in silico pipeline. Five microRNAs identified using an in silico approach alongside their seven target genes from our previous study were used as datasets in this study. Furthermore, the secondary structure and the thermodynamic energies of the microRNAs were revealed by Mfold algorithm. The triplex binding ability of the oligonucleotide with the target promoters were analyzed by Trident. Finally, evolutionary stage-specific somatic events and co-expression analysis of the target genes in CRC were analyzed by SEECancer and GeneMANIA plugin in Cytoscape. Four of the five microRNAs have the potential to form more than one secondary structure. The ranges of the observed/expected ratio of CpG dinucleotides of these genes range from 0.60 to 1.22. Three of the candidate microRNA were capable of forming multiple triplexes along with three of the target mRNAs. Four of the total targets were involved in either early or metastatic stage-specific events while three other genes were either a product of antecedent or subsequent events of the four genes implicated in CRC. The secondary structure of the candidate microRNAs can be used to explain the different degrees of genetic regulation in CRC due to their conformational role to modulate target interaction. Furthermore, due to the regulation of important genes in the CRC pathway and the enrichment of the microRNA with triplex binding sites, they may be a useful diagnostic biomarker for the disease subtype.

• CRC
• functional predictions
• in silico analysis
• microRNA
• triplex binding site

• Acyltransferases
• Adaptor Proteins, Signal Transducing/genetics
• Adaptor Proteins, Signal Transducing/metabolism
• Apoptosis
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Cell Proliferation
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic
• Humans
• Liposarcoma/metabolism
• Liposarcoma/mortality
• Liposarcoma/pathology
• Neoplasm Recurrence, Local/metabolism
• Neoplasm Recurrence, Local/mortality
• Neoplasm Recurrence, Local/pathology
• Prognosis
• Signal Transduction
• Survival Rate
• Tissue Inhibitor of Metalloproteinase-1/genetics
• Tissue Inhibitor of Metalloproteinase-1/metabolism
• Tissue Inhibitor of Metalloproteinases/genetics
• Tissue Inhibitor of Metalloproteinases/metabolism
• Transcription Factors/genetics
• Transcription Factors/metabolism
• Tumor Cells, Cultured
• YAP-Signaling Proteins
• Tissue Inhibitor of Metalloproteinase-4

Liposarcoma is a malignant neoplasm of fat tissue. Well-differentiated and dedifferentiated liposarcoma (WDL/DDL) represent the two most clinically observed histotypes occurring in middle-aged to older adults, particularly within the retroperitoneum or extremities. WDL/DDL are thought to represent the broad spectrum of one disease, as they are both associated with the amplification in the chromosomal 12q13-15 region that causes MDM2 and CDK4 overexpression, the most useful predictor for liposarcoma diagnosis. In comparison to WDL, DDL contains additional genetic abnormalities, principally coamplifications of 1p32 and 6q23, that increase recurrence and metastatic rate. In this review, we discuss the xenograft and transgenic animal models generated for studying progression of WDL/DDL, highlighting utilities and pitfalls in such approaches that can facilitate or impede the development of new therapies.

• liposarcoma
• transgenic animal model
• xenograft

• AKT/mTOR
• Osteosarcoma
• XIST
• miR-375-3p

• CCAAT/enhancer binding protein β
• inflammatory cytokines
• intervertebral disk degeneration
• microRNA 155
• nucleus pulposus

Sarcomas are malignant heterogeneous tumors of mesenchymal derivation. Dedifferentiated liposarcoma (DDLPS) is aggressive with recurrence in 80% and metastasis in 20% of patients. We previously found that miR-133a was significantly underexpressed in liposarcoma tissues. As this miRNA has recently been shown to be a tumor suppressor in many cancers, the objective of this study was to characterize the biological and molecular consequences of miR-133a underexpression in DDLPS.

Real-time PCR was used to evaluate expression levels of miR-133a in human DDLPS tissue, normal fat tissue, and human DDLPS cell lines. DDLPS cells were stably transduced with miR-133a vector to assess the effects in vitro on proliferation, cell cycle, cell death, migration, and metabolism. A Seahorse Bioanalyzer system was also used to assess metabolism in vivo by measuring glycolysis and oxidative phosphorylation (OXPHOS) in subcutaneous xenograft tumors from immunocompromised mice.

miR-133a expression was significantly decreased in human DDLPS tissue and cell lines. Enforced expression of miR-133a decreased cell proliferation, impacted cell cycle progression kinetics, decreased glycolysis, and increased OXPHOS. There was no significant effect on cell death or migration. Using an in vivo xenograft mouse study, we showed that tumors with increased miR-133a expression had no difference in tumor growth compared to control, but did exhibit an increase in OXPHOS metabolic respiration.

Based on our collective findings, we propose that in DDPLS, loss of miR-133a induces a metabolic shift due to a reduction in oxidative metabolism favoring a Warburg effect in DDLPS tumors, but this regulation on metabolism was not sufficient to affect DDPLS.

The online version of this article (10.1186/s12935-018-0583-2) contains supplementary material, which is available to authorized users.

• Dedifferentiated liposarcoma
• Metabolism
• Sarcoma
• miR-133a

Casein kinase 1α (CK1α) is a multifunctional protein belonging to the CK1 protein family that is conserved in eukaryotes from yeast to humans. It regulates signaling pathways related to membrane trafficking, cell cycle progression, chromosome segregation, apoptosis, autophagy, cell metabolism, and differentiation in development, circadian rhythm, and the immune response as well as neurodegeneration and cancer. Given its involvement in diverse cellular, physiological, and pathological processes, CK1α is a promising therapeutic target. In this review, we summarize what is known of the biological functions of CK1α, and provide an overview of existing challenges and potential opportunities for advancing theranostics.

• Autophagy
• Casein kinase 1α
• Cell cycle
• Hedgehog signaling
• Host defense response
• NF-κB signaling
• Neurodegenerative disease
• Wnt/β-catenin signaling

Liposarcoma (LPS) is a malignancy with extreme heterogeneity and thus optimization towards personalizing patient prognosis and treatment is essential. Here, we evaluated miR-155, miR-21, miR-143, miR-145 and miR-451 that are implicated in LPS, as novel FFPE tissue biomarkers.

A total of 83 FFPE tissue specimens from primary LPS and lipomas (LPM) were analyzed. A proteinase K incubation-Trizol treatment coupled protocol was used for RNA isolation. After polyadenylation of total RNA and reverse transcription, expression analysis of 9 candidate reference and 5 target miRNAs was performed by qPCR. Genorm and NormFinder were used for finding the most suitable molecules for normalization. Survival analyses were performed in order to evaluate the prognostic potential of miRNAs.

MiR-103 and miR-191 are most suitable for normalization of miRNA expression in LPS. MiR-155 and miR-21 are clearly overexpressed (P<0.001) in LPS compared with LPM specimens, whereas miR-145 (P<0.001), miR-143 (P =0.008) and miR-451 (P=0.037) are underexpressed. MiR-155 (P=0.007) and miR-21 (P=0.029) are differentially expressed between well-differentiated, dedifferentiated, myxoid/round cell and pleomorphic LPs tumor subtypes. MiR-155 represents a novel independent indicator of unfavorable prognosis in LPS (HR = 2.97, 95% CI = 1.23–7.17, P = 0.016).

• liposarcoma
• miR-155
• miRNA expression normalization
• miRNAs
• prognostic biomarker

• E7389
• EMBRACE
• breast cancer
• eribulin mesylate
• halichondrin B
• miRNAs
• microtubule inhibitor
• soft tissue sarcoma

To investigate the effect of microRNA (miR)-155 on colon cancer chemoresistance to cisplatine and its mechanism. Reverse transcription quantitative polymerase chain reaction was used to measure the levels of miR-155 and forkhead box O3 (FOXO3) in colon cancer specimens and cell lines. Overexpression of miR-155 and miR-155 inhibitor were transfected into colon cancer cell lines to investigate its role of chemoresistance to cisplatin in colon cancer. MTS assays were used to analyse cell viability in vitro. In vivo tumor formation assays were performed in C57BL/6 wild type and miR-155 knockout mice (miR-155-/-). A luciferase reporter assay was used to measure the translation of FOXO3. Additionally, the expression of FOXO3 was detected by western blot analysis. It was identified that miR-155 was markedly upregulated in colon cancer tissue and cell lines. Overexpression of miR-155 enhanced colon cancer cell chemoresistance to cisplatin in vitro and tumorigenesis in vivo. In addition, overexpression of miR-155 was associated with decreased levels of FOXO3, primarily through inhibiting the expression of FOXO3 to increase colon cancer resistanec to cisplatin. The present study demonstrated that miR-155 increased colon cancer drug resistance and decreased FOXO3 expression in vivo and in vitro. This may provide a novel method for the treatment of drug-resistant colon cancer.

• chemoresistance
• cisplatin
• colon cancer
• forkhead box O3
• microRNA-155

Herein, we aimed at identifying global transcriptome microRNA (miRNA) changes and miRNA target genes in lung adenocarcinoma. Samples were selected as training (N = 24) and independent validation (N = 34) sets. Tissues were microdissected to obtain >90% tumor or normal lung cells, subjected to miRNA transcriptome sequencing and TaqMan quantitative PCR validation. We further integrated our data with published miRNA and mRNA expression datasets across 1,491 lung adenocarcinoma and 455 normal lung samples. We identified known and novel, significantly over- and under-expressed (p ≤ 0.01 and FDR≤0.1) miRNAs in lung adenocarcinoma compared to normal lung tissue: let-7a, miR-10a, miR-15b, miR-23b, miR-26a, miR-26b, miR-29a, miR-30e, miR-99a, miR-146b, miR-181b, miR-181c, miR-421, miR-181a, miR-574 and miR-1247. Validated miRNAs included let-7a-2, let-7a-3, miR-15b, miR-21, miR-155 and miR-200b; higher levels of miR-21 expression were associated with lower patient survival (p = 0.042). We identified a regulatory network including miR-15b and miR-155, and transcription factors with prognostic value in lung cancer. Our findings may contribute to the development of treatment strategies in lung adenocarcinoma.

• lung adenocarcinoma
• microRNAs
• molecular targets
• transcription factor networks
• transcriptome sequencing

Mounting evidence has indicated microRNA (miR) dysregulation and the Wnt/β-catenin signaling pathway jointly drive carcinogenesis, cancer metastasis, and drug-resistance. The current review will focus on the role of the crosstalk between miRs and the Wnt/β-catenin signaling pathway in cancer development. MiRs were found to activate or inhibit the canonical Wnt pathway at various steps. On the other hand, Wnt activation increases expression of miR by directly binding to its promoter and activating transcription. Moreover, there are mutual feedback loops between some miRs and the Wnt/β-catenin signaling pathway. Clinical trials of miR-based therapeutic agents are investigated for solid and hematological tumors, however, challenges concerning low bioavailability and possible side effects must be overcome before the final clinical application. This review will describe current understanding of miR crosstalk with the Wnt/β-catenin signaling cascade. Better understanding of the regulatory network will provide insight into miR-based therapeutic development.

• Wnt/β-catenin signaling pathway
• cancer
• microRNA

• microRNAs
• soft tissue sarcoma
• tumourigenesis

• tumor microenvironment
• blood
• il-6
• nf-κb
• macrophages

• Animals
• Case-Control Studies
• Cell Line, Tumor
• Cell Proliferation/genetics
• Disease Progression
• Exosomes/metabolism
• HEK293 Cells
• Humans
• Liposarcoma/blood
• Liposarcoma/genetics
• Liposarcoma/pathology
• Mice
• Mice, Inbred C57BL
• MicroRNAs/metabolism
• Transfection

• P30 CA016058 NCI NIH HHS
• R35 CA197706 NCI NIH HHS
• U54 CA168512 NCI NIH HHS

• CK1α
• GSK3β
• MSCs
• mesenchymal stem cells
• miR-9-5p
• migration
• β-catenin signaling pathway

• CBX7
• Colon carcinoma
• KRAS
• miR-155

• Animals
• Cell Line
• Colonic Neoplasms/genetics
• Colonic Neoplasms/metabolism
• Fibroblasts/metabolism
• Gene Expression Profiling
• Gene Expression Regulation
• Genes, ras
• Humans
• Mice
• MicroRNAs/metabolism
• Polycomb Repressive Complex 1/metabolism
• Signal Transduction

• PRIN-MIUR
• PNR-CNR Aging Program
• POR Campania FSE
• CNR Flagship Projects
• AIRC