• APJ
• apelin
• cancer
• chemoresistance
• hallmarks of cancer

• Humans
• Apelin/metabolism
• Apelin/genetics
• Neoplasms/metabolism
• Neoplasms/pathology
• Neoplasms/genetics
• Apelin Receptors/metabolism
• Apelin Receptors/genetics
• Animals
• Signal Transduction

• colon cancer
• molecular tumor markers
• prognosis
• prognostic biomarkers
• small noncoding RNA
• tRNA fragment

• colon cancer
• microRNA
• molecular tumor markers
• prognosis
• prognostic biomarkers
• small non-coding RNA

• Chemoresistance
• Colorectal cancer
• Migration
• Proliferation
• SIRT4
• miR-15a-5p

• Breast cancer
• Hsp
• miRNA
• miRNA network

• Biology
• Breast Neoplasms/genetics
• Female
• HSP27 Heat-Shock Proteins
• HSP70 Heat-Shock Proteins
• HSP90 Heat-Shock Proteins
• Heat-Shock Proteins
• Humans
• MicroRNAs/genetics

• myeloma
• gene regulation

• Humans
• MicroRNAs/genetics
• Multiple Myeloma/genetics
• Multiple Myeloma/pathology

• Chengde Technology Research and Development Program (No. 201804A079).

Oxidized low-density lipoprotein (ox-LDL) is a significant risk factor for various brain vascular diseases. Circular RNA (circRNA) is involved in the pathogenesis of brain vascular diseases. This study revealed the roles of circ_CHFR in ox-LDL-mediated cell proliferation, apoptosis, and endothelial-to-mesenchymal transition (EndoMT). Our results showed that circ_CHFR and EGFR expressions were dramatically upregulated, while miR-15a-5p expression was downregulated in ox-LDL-induced human brain microvessel endothelial cells (HBMECs) relative to control groups. circ_CHFR knockdown hindered the effects of ox-LDL exposure on cell proliferation, cell cycle, apoptosis, and EndoMT in HBMECs, whereas these impacts were abolished by miR-15a-5p inhibitor. In addition, circ_CHFR functioned as a sponge of miR-15a-5p and miR-15a-5p bound to EGFR. Thus, we concluded that circ_CHFR silencing hindered ox-LDL-mediated cell proliferation, apoptosis, and EndoMT by downregulating EGFR expression through sponging miR-15a-5p in HBMECs. Our findings provide a new mechanism for studying circRNA-directed therapy in ox-LDL-induced human brain vascular diseases.

• EGFR
• HBMECs
• circ_CHFR
• miR-15a-5p
• ox-LDL

Tubular adenocarcinoma of the colon, which originates from the epithelium of the glands, is a major health concern worldwide. However, it is difficult to detect at an early stage. The lack of biomarkers is a main barrier to the diagnosis and treatment of tubular adenocarcinoma. Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted protein that induces the expression of matrix metalloproteinase-9 (MMP-9) and is involved in various tumors. NGAL and MMP-9 have been reported to be associated with tumorigenesis and development. They may have potential as biomarkers for diagnosis of tubular adenocarcinoma of the colon.

To determine whether NGAL and MMP-9 can be used as potential biomarkers to indicate the progression of tubular adenocarcinoma of the colon.

Samples were collected from surgically excised tissue from various patients. The content of pro-gastrin-releasing peptide (pro-GRP) in the serum was measured by an electrochemiluminescence immunoassay. The expression patterns of NGAL and MMP-9 and the relationship between NGAL and MMP-9 were examined by quantitative real-time PCR, Western blotting and immunohistochemical analysis.

In this study, we found that NGAL and MMP-9 can be used as biomarkers for the detection of tubular adenocarcinoma of the colon and that their combination improved diagnostic accuracy. By analyzing the expression of NGAL in tubular adenocarcinoma at different levels, we found that NGAL expression was significantly upregulated in primary tubular adenocarcinoma tissues compared with normal tissues. The upregulation of NGAL expression was strongly correlated with both the degree of differentiation and the disease stage (I–III), indicating that NGAL could serve as a diagnostic biomarker for tubular adenocarcinoma. When using NGAL as a biomarker for diagnosis, the accuracy was similar to that achieved with the widely used biomarker pro-GRP, suggesting that NGAL is reliable. Moreover, the expression of MMP-9 was also strongly correlated with the differentiation stage, demonstrating that MMP-9 could be used as a biomarker to indicate the progression of tubular adenocarcinoma of the colon. More importantly, the combination of NGAL and MMP-9 produced a more accurate diagnosis of tubular adenocarcinoma, and these results were further confirmed by immunohistochemical analysis of tissue sections.

Our study demonstrated that both NGAL and MMP-9 can be used as biomarkers for the diagnosis of colon tubular adenocarcinoma and that the results could be further improved by combining them.

• Tubular adenocarcinoma
• Colon
• Neutrophil gelatinase-associated lipocalin
• Matrix metalloproteinase-9
• Biomarker

Hepatocellular carcinoma (HCC) cells-secreted exosomes (exo) could stimulate M2 macrophage polarization and promote HCC progression, but the related mechanism of long non-coding RNA distal-less homeobox 6 antisense 1 (DLX6-AS1) with HCC-exo-mediated M2 macrophage polarization is largely ambiguous. Thereafter, this research was started to unearth the role of DLX6-AS1 in HCC-exo in HCC through M2 macrophage polarization and microRNA (miR)-15a-5p/C-X-C motif chemokine ligand 17 (CXCL17) axis.

DLX6-AS1, miR-15a-5p and CXCL17 expression in HCC tissues and cells were tested. Exosomes were isolated from HCC cells with overexpressed DLX6-AS1 and co-cultured with M2 macrophages. MiR-15a-5p/CXCL17 down-regulation assays were performed in macrophages. The treated M2 macrophages were co-cultured with HCC cells, after which cell migration, invasion and epithelial mesenchymal transition were examined. The targeting relationships between DLX6-AS1 and miR-15a-5p, and between miR-15a-5p and CXCL17 were explored. In vivo experiment was conducted to detect the effect of exosomal DLX6-AS1-induced M2 macrophage polarization on HCC metastasis.

Promoted DLX6-AS1 and CXCL17 and reduced miR-15a-5p exhibited in HCC. HCC-exo induced M2 macrophage polarization to accelerate migration, invasion and epithelial mesenchymal transition in HCC, which was further enhanced by up-regulated DLX6-AS1 but impaired by silenced DLX6-AS1. Inhibition of miR-15a-5p promoted M2 macrophage polarization to stimulate the invasion and metastasis of HCC while that of CXCL17 had the opposite effects. DLX6-AS1 mediated miR-15a-5p to target CXCL17. DLX6-AS1 from HCC-exo promoted metastasis in the lung by inducing M2 macrophage polarization in vivo.

DLX6-AS1 from HCC-exo regulates CXCL17 by competitively binding to miR-15a-5p to induce M2 macrophage polarization, thus promoting HCC migration, invasion and EMT.

The online version contains supplementary material available at 10.1186/s13046-021-01973-z.

• C-X-C motif chemokine ligand 17
• Hepatocellular carcinoma
• Hepatocellular carcinoma cell-secreted exosomes
• Long non-coding RNA distal-less homeobox 6 antisense 1
• M2 macrophages
• microRNA-15a-5p

• Adipocyte enhancer binding protein 1
• Glioma
• Long intergenic non-protein coding RNA 511
• Malignant phenotype
• miR-15a-5p

• Wnt/β-catenin
• endometrial carcinoma
• epithelial-mesenchymal transition
• microRNA-15a-5p
• vascular endothelial growth factor A

• Colorectal neoplasms
• MicroRNA
• Oncology
• Prognosis
• Systematic review

• Biomarkers, Tumor/metabolism
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/mortality
• Disease-Free Survival
• Gene Expression Regulation, Neoplastic/genetics
• Genes, Tumor Suppressor
• Humans
• Lymphatic Metastasis/genetics
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Prognosis

Colorectal cancer (CRC) is one of the most commonly diagnosed and leading causes of cancer mortality worldwide, and the prognosis of patients with CRC remains unsatisfactory. Basic transcription factor 3 (BTF3) is an oncogene and hazardous prognosticator in CRC. Although two distinct functional mechanisms of BTF3 in different cancer types have been reported, its role in CRC is still unclear. In this study, we aimed to molecularly characterize the oncogene BTF3 and its targets in CRC. Here, we first identified the transcriptional targets of BTF3 by applying combined RNA-Seq and ChIP-Seq analysis, identifying CHD1L as a transcriptional target of BTF3. Thereafter, we conducted immunoprecipitation (IP)-MS and E3 ubiquitin ligase analysis to identify potential interacting targets of BTF3 as a subunit of the nascent-polypeptide-associated complex (NAC). The analysis revealed that BTF3 might also inhibit E3 ubiquitin ligase HERC2-mediated p53 degradation. Finally, miRNAs targeting BTF3 were predicted and validated. Decreased miR-497-5p expression is responsible for higher levels of BTF3 post-transcriptionally. Collectively, we concluded that BTF3 is an oncogene, and there may exist a transcription factor and NAC-related proteolysis mechanism in CRC. This study provides a comprehensive basis for understanding the oncogenic mechanisms of BTF3 in CRC.

• CHD1L
• HERC2
• MiR-497
• TP53
• basic transcription factor 3 (BTF3)
• colorectal cancer

Colorectal carcinoma (CRC) is one of the most common malignant tumors. The present study aimed to investigate a non-invasive molecular marker that can evaluate the diagnosis and potential molecular mechanism of CRC. Microarray assays and reverse transcription-quantitative PCR analysis demonstrated that microRNA (miR)-325-3p expression was significantly increased in both tissues and serum samples of patients with CRC. In addition, miR-325-3p expression in the tissues and serum was significantly associated with differentiation, TNM stage and lymph node metastasis. The results of the dual-luciferase reporter assay and western blot analysis revealed that cytokeratin 18 (CK18) is a target gene of miR-325-3p. Furthermore, treatment with transforming growth factor (TGF)-β increased miR-325-3p expression in a time-dependent manner. Conversely, TGF-β decreased CK18 expression at 48 and 72 h. Western blot analysis demonstrated that TGF-β1 significantly decreased the expression of the epithelial marker, CK18, and increased the expression of the mesenchymal markers, α-SMA and vimentin. Notably, these effects were reversed following inhibition of miR-325-3p expression. Taken together, the results of the present study suggest that miR-325-3p is a key regulator of TGF-β-induced CK18 downregulation. Thus, elevated levels of miR-325-3p is an important factor affecting epithelial-to-mesenchymal transition, and is likely to be a molecular marker in the progression of CRC and act as a potential therapeutic target.

• colorectal carcinoma
• cytokeratin 18
• microRNA-325-3p

• NSCLC
• PSAT1
• Progression
• lncRNA MEG8
• miR-15a-5p
• miR-15b-5p

• GERD
• biomarker
• esophageal cancer
• miRNA

miRNAs play role in various diseases and can also modulate therapy response. Our aim was to identify predictive miRNAs in platinum treated squamous cell carcinomas (SCC). Using a set of 266 squamous cancer samples we uncovered 16, 103, and 9 miRNAs correlated to chemotherapy response in the cervical, head and neck, and lung squamous cell carcinomas, respectively. By employing a logistic regression model, a signature comprising a set of six miRNAs was established capable to predict chemotherapy response with an AUC of 0.897. Our results show common molecular features of SCC tumors and pinpoint the most important miRNAs related to treatment outcome.

Introduction: Squamous cell carcinomas (SCC) are a major subgroup of malignant tumors with a platinum-based first-line systematic chemotherapy. miRNAs play a role in various diseases and modulate therapy response as well. The aim of this study was to identify predictive miRNAs in platinum-treated SCCs. Methods: miRNA expression data of platinum-treated head and neck (HNSC), cervical (CESC) and lung (LUSC) cancer were collected from the TCGA repositories. Treatment response was defined based on presence or absence of disease progression at 18 months. Responder and nonresponder cohorts were compared using Mann–Whitney and Receiver Operating Characteristic tests. Logistic regression was developed to establish a predictive miRNA signature. Significance was set at FDR < 5%. Results: The integrated database includes 266 SCC patient samples with platinum-based therapy and available follow-up. We uncovered 16, 103, and 9 miRNAs correlated to chemotherapy response in the CESC, HNSC, and LUSC cohorts, respectively. Eight miRNAs overlapped between the CESC and HNSC subgroups, and three miRNAs overlapped between the LUSC and HNSC subgroups. We established a logistic regression model in HNSC and CESC which included six miRNAs: hsa-miR-5586 (Exp (B): 2.94, p = 0.001), hsa-miR-632 (Exp (B): 10.75, p = 0.002), hsa-miR-2355 (Exp (B): 0.48, p = 0.004), hsa-miR-642a (Exp (B): 2.22, p = 0.01), hsa-miR-101-2 (Exp (B): 0.39, p = 0.013) and hsa-miR-6728 (Exp (B): 0.21, p = 0.016). The model using these miRNAs was able to predict chemotherapy resistance with an AUC of 0.897. Conclusions: We performed an analysis of RNA-seq data of squamous cell carcinomas samples and identified significant miRNAs correlated to the response against platinum-based therapy in cervical, head and neck, and lung tumors.

• cancer
• carboplatin
• cervical cancer
• chemotherapy
• cisplatin
• head and neck cancer
• logistic regression
• lung cancer
• miRNA
• receiver operator characteristics

• cell adhesion molecule 1
• cell proliferation
• glioblastoma
• invasion
• microRNA-15a-5p

The present study aimed to investigate the role of microRNA (miR)-15a-5p in the pathogenesis of acute lung injury induced by traumatic hemorrhagic shock (THS), and to explore the underlying molecular mechanism. The expression level of miR-15a-5p was detected using reverse transcription-quantitative (RT-qPCR) and the association between miR-15a-5p and TNFAIP3-interacting protein 2 (TNIP2) was revealed using TargetScan and dual luciferase reporter assays. To investigate the effect of miR-15a-5p on THS-induced acute lung injury, a THS rat model was established. Lung capillary permeability and lung edema were then determined. Moreover, proinflammatory factors in the bronchoalveolar lavage fluid (BALF) and serum of the THS rat model were detected using ELISA. In addition, protein levels in the current study were measured via western blotting. It was revealed that miR-15a-5p was significantly upregulated in both patients with THS and samples from the THS rat model. TNIP2 represents a direct target of miR-15a-5p, and it was downregulated in both patients with THS and the THS rat model. Further analyses indicated that downregulation of miR-15a-5p significantly relieved acute lung injury induced by THS, evidenced by a decreased ratio of Evan's blue dye (EBD) in the BALF to EBD in plasma of THS rats, decreased lung permeability index and reduced lung wet/dry ratio. Inhibition of miR-15a-5p also decreased THS-induced upregulation of pro-inflammatory factors. Furthermore, the data revealed that THS-induced NF-κB activation in the lung tissues of rats was inhibited by miR-15a-5p knockdown. Moreover, it was demonstrated that all the effects of miR-15a-5p on THS rats were ablated following TNIP2 silencing. Taken together, the data of the current study indicate that miR-15a-5p downregulation serves a protective role in THS-induced acute lung injury via directly targeting TNIP2.

• TNIP2
• inflammatory response
• lung injury
• microRNA-15a-5p
• trauma-hemorrhagic shock

• Head and neck cancer
• Molecular tumor biomarker
• Prognostic biomarker
• Real-time quantitative PCR
• microRNA (miRNA)

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/metabolism
• Carcinoma, Squamous Cell
• Female
• Gene Expression
• Gene Expression Regulation, Neoplastic
• Humans
• Laryngeal Neoplasms/genetics
• Laryngeal Neoplasms/pathology
• Lymph Nodes/pathology
• Lymphatic Metastasis
• Male
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Middle Aged
• Prognosis
• Squamous Cell Carcinoma of Head and Neck/genetics
• Squamous Cell Carcinoma of Head and Neck/pathology

• KIF23
• PVT1
• Prostate cancer
• miR-15a-5p

• Apoptosis
• Hippocampus neuron
• Temporal lobe epilepsy
• Viability
• miR-15a-5p

• Animals
• Apoptosis/genetics
• Biomarkers/analysis
• Cell Survival/genetics
• Child
• Epilepsy, Temporal Lobe/genetics
• Epilepsy, Temporal Lobe/pathology
• Female
• Hippocampus/metabolism
• Hippocampus/pathology
• Humans
• Male
• MicroRNAs/metabolism
• Neurons/metabolism
• Neurons/pathology
• Rats
• Rats, Wistar

Previous literature has revealed long non-coding RNAs (lncRNAs) are crucial regulators for cell functions and gene expression. LncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) was reported as a biological suppressor in several types of human cancers, yet relevant mechanisms and biological effects of FENDRR with regards to cervical cancer (CC) are not explored until now.

In this study, quantitative real-time polymerase chain reaction (qRT-PCR) analysis detected gene expression in tissues and cells. Gain- or loss-of-function experiments revealed the biological effects of FENDRR and miR-15a/b-5p on CC cell functions. Bioinformatics tools were used to predict the relevant genes. Mechanism experiments including RNA immunoprecipitation (RIP) assay, pull down assay and luciferase reporter assay depicted the binding situation and coexistence of indicated genes.

FENDRR was downregulated in CC tissues and cells, which suppressed CC progression. MiR-15a-5p and miR-15b-5p shared binding sites with FENDRR and had interaction with FENDRR. Tubulin alpha1A (TUBA1A) was downregulated in CC tissues and positively modulated by FENDRR. TUBA1A was the target of miR-15a/b-5p. TUBA1A silencing rescued the effect of FENDRR overexpression on CC cell growth and migration.

FENDRR inhibits CC progression through upregulating TUBA1A in a miR-15a/b-5p-dependent manner.

• Cervical cancer
• FENDRR
• TUBA1A
• miR-15a/b-5p

• E2F3
• miR-15a-5p
• proliferation
• vitamin D3

Activation of acid sphingomyelinase (SMPD1) and the generation of ceramide is a critical regulator of apoptosis in response to cellular stress including radiation. Endothelial SMPD1 has been shown to regulate tumor responses to radiation therapy. We show here that the SMPD1 gene is regulated by a microRNA (miR), miR-15a, in endothelial cells (ECs). Standard low dose radiation (2 Gy) upregulates miR-15a and decreases SMPD1 levels. In contrast, high dose radiation (10 Gy and above) decreases miR-15a and increases SMPD1. Ectopic expression of miR-15a decreases both mRNA and protein levels of SMPD1. Mimicking the effects of high dose radiation with a miR-15a inhibitor decreases cell proliferation and increases active Caspase-3 & 7. Mechanistically, inhibition of miR-15a increases inflammatory cytokines, activates caspase-1 inflammasome and increases Gasdermin D, an effector of pyroptosis. Importantly, both systemic and vascular-targeted delivery of miR-15a inhibitor decreases angiogenesis and tumor growth in a CT26 murine colorectal carcinoma model. Taken together, our findings highlight a novel role for miR mediated regulation of SMPD1 during radiation responses and establish proof-of-concept that this pathway can be targeted with a miR inhibitor.

• HSPB3
• colorectal cancer
• molecular tumor markers
• prognosis
• prognostic biomarkers

• colon cancer
• gastrointestinal cancer
• molecular tumor markers
• prognosis
• prognostic biomarkers
• quantitative real-time PCR (qPCR)

• Head and neck cancer
• Laryngeal cancer
• Prognostic tumor biomarker

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Female
• Gene Expression
• Humans
• Immunohistochemistry
• Laryngeal Neoplasms/diagnosis
• Laryngeal Neoplasms/genetics
• Laryngeal Neoplasms/metabolism
• Laryngeal Neoplasms/mortality
• Male
• Middle Aged
• Prognosis
• Receptor, Notch1/genetics
• Receptor, Notch1/metabolism
• Repressor Proteins/genetics
• Repressor Proteins/metabolism
• Squamous Cell Carcinoma of Head and Neck/diagnosis
• Squamous Cell Carcinoma of Head and Neck/genetics
• Squamous Cell Carcinoma of Head and Neck/metabolism
• Squamous Cell Carcinoma of Head and Neck/mortality
• Survival Rate
• Trans-Activators/genetics
• Trans-Activators/metabolism
• Vimentin/genetics
• Vimentin/metabolism

• colon cancer
• microRNA-28 (miRNA-28)
• molecular tumor markers
• prognosis
• prognostic biomarkers
• real-time quantitative real-time PCR (RT-qPCR)

• Chondrocytes/metabolism
• Chondrocytes/pathology
• Gene Expression Regulation
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Osteoarthritis/genetics
• Osteoarthritis/metabolism
• Osteoarthritis/pathology
• Parathyroid Hormone-Related Protein/biosynthesis
• Parathyroid Hormone-Related Protein/genetics

• Apoptosis
• animal model
• osteoarthritis (OA)
• quantitative polymerase chain reaction (qPCR)
• statistical analysis

• Biomarker
• long non-coding RNA (lncRNA)
• small non-coding RNA (sncRNA)
• transcriptomics

• Bioinformatics
• alternative splicing
• isoform
• next-generation sequencing (NGS)
• splice variant

• colorectal cancer
• meta-analysis
• microRNA
• prognosis