• statistical methods
• software
• computational models

• MicroRNAs/genetics
• MicroRNAs/metabolism
• Humans
• Single-Cell Analysis/methods
• Transcriptome
• Gene Expression Profiling/methods
• Multiple Sclerosis/genetics
• Leukocytes, Mononuclear/metabolism
• Gene Expression Regulation

• The RESCUER project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant agreement No. 847912

• Engineered exosomes
• Ferroptosis
• Mesenchymal stem cells
• MiR-486-5p
• Pulmonary fibrosis
• Radiation-induced pulmonary injury
• SARS-CoV-2-S-RBD

• Exosomes/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Ferroptosis
• Animals
• Mesenchymal Stem Cells/metabolism
• Humans
• Mice
• Pulmonary Fibrosis/therapy
• SARS-CoV-2
• Angiotensin-Converting Enzyme 2/metabolism
• Angiotensin-Converting Enzyme 2/genetics
• Lung Injury/therapy
• COVID-19/therapy
• Lung/pathology
• Radiation Injuries/therapy
• Radiation Injuries/metabolism
• Male

• H2024103005 Natural Science Foundation of Hebei Province
• 22567663H Science and Technology Enhancement Program of Heibei Province
• 82073489 National Natural Science Foundation of China
• ZR2020MH327 Natural Science Foundation of Shandong Province

• MT: Regular Issue
• epigenetics
• lncRNAs
• meningioma
• microRNAs
• molecular signatures
• noncoding RNAs
• therapeutics

• exosome
• human breast milk
• microbial defense
• proteomics
• small RNA sequencing

• NRF-2021R1F1A1061287 National Research Foundation of Korea
• NRF-2021R1A6A3A13045991 National Research Foundation of Korea
• D.H.K. Chung-Ang University Graduate Research Scholarship in 2023

• cancer immunotherapy
• exosomes
• immune system
• infectious disease
• vaccine development

• Humans
• Exosomes/metabolism
• Vaccine Development
• Tumor Microenvironment
• Neoplasms/pathology
• Cell Communication

• U24 MD015970 NIMHD NIH HHS
• U54 MD007592 NIMHD NIH HHS
• U54MD007592 NIMHD NIH HHS
• PR210153 Cancer Prevention and Research Institute of Texas
• U54MD007592 NIMHD NIH HHS
• National Institute on Minority Health and Health Disparities

• TAp63
• TPM4
• Tropomyosins
• circulating miRs
• colon carcinoma (CRC)
• miR-133a
• miRNAs
• physical activity

• Actin Cytoskeleton/genetics
• Carcinogenesis/genetics
• Cell Differentiation/genetics
• Cell Line, Tumor
• Cell Proliferation/genetics
• Colonic Neoplasms/genetics
• Colonic Neoplasms/pathology
• Cytoskeleton/genetics
• Gene Expression Regulation, Neoplastic/genetics
• Humans
• MicroRNAs/genetics
• Muscle Cells/cytology
• Muscle Development/genetics
• Muscle, Skeletal/growth & development
• Muscle, Skeletal/metabolism
• Stress Fibers/genetics
• Transcription Factors/genetics
• Tropomyosin/genetics
• Tumor Suppressor Proteins/genetics

Different miRNA profiling protocols and technologies introduce differences in the resulting quantitative expression profiles. These include differences in the presence (and measurability) of certain miRNAs. We present and examine a method based on quantile normalization, Adjusted Quantile Normalization (AQuN), to combine miRNA expression data from multiple studies in breast cancer into a single joint dataset for integrative analysis. By pooling multiple datasets, we obtain increased statistical power, surfacing patterns that do not emerge as statistically significant when separately analyzing these datasets. To merge several datasets, as we do here, one needs to overcome both technical and batch differences between these datasets. We compare several approaches for merging and jointly analyzing miRNA datasets. We investigate the statistical confidence for known results and highlight potential new findings that resulted from the joint analysis using AQuN. In particular, we detect several miRNAs to be differentially expressed in estrogen receptor (ER) positive versus ER negative samples. In addition, we identify new potential biomarkers and therapeutic targets for both clinical groups. As a specific example, using the AQuN-derived dataset we detect hsa-miR-193b-5p to have a statistically significant over-expression in the ER positive group, a phenomenon that was not previously reported. Furthermore, as demonstrated by functional assays in breast cancer cell lines, overexpression of hsa-miR-193b-5p in breast cancer cell lines resulted in decreased cell viability in addition to inducing apoptosis. Together, these observations suggest a novel functional role for this miRNA in breast cancer. Packages implementing AQuN are provided for Python and Matlab: https://github.com/YakhiniGroup/PyAQN.

This work demonstrates a practical approach to the joint-analysis of multiple miRNA expression profiling datasets acquired with different measurement technologies. The use of different platforms in miRNA profiling can lead to major differences in results. In particular, some miRNA species are less amenable to detection and quantification by certain platforms or designs. Our approach, termed AQuN, combines quantile normalization with special attention to missing entities, to normalize miRNA expression across datasets, technologies, designs and platforms. As we show, our proposed approach uncovers patterns of interest that would not have emerged as statistically significant when analyzing the datasets individually or with other standard-practice normalization methods.

Amongst our findings, we noted a previously undocumented miRNA that is significantly over-expressed in samples from estrogen-receptor positive breast cancer patients as compared to samples from estrogen-receptor negative patients. We further investigated this miRNA, hsa-miR-193b-5p, and experimentally show, in cell lines, that its expression level impacts the viability of tumor cells. AQuN is available to the community in the form of Python and Matlab packages. The joint-processed data is also made available for further investigation.

• Algorithms
• Biomarkers/metabolism
• Biomarkers, Tumor/genetics
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Cell Line, Tumor
• Computer Simulation
• Estrogen Receptor alpha/metabolism
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• MCF-7 Cells
• MicroRNAs/metabolism
• Oligonucleotide Array Sequence Analysis
• Programming Languages
• RNA, Messenger/genetics

• MiRNA/MicroRNA
• OncomiR
• aggressive
• inflammatory breast cancer
• tumor suppressor

MicroRNAs are involved in various pathologies including cancer. The aim of the study was to assess the level of expression of miR-96-5p, -134-5p, -181b-5p, -200b-3p in FFPE samples of prostate cancer, adjacent cancer-free tissue, and benign prostatic hyperplasia. Samples of 23 FFPE prostate cancer and 22 benign prostatic hyperplasias were dissected and HE stained. Compartments of tumor tissue and adjacent healthy glandular tissue were isolated from each sample using Laser Capture Microdissection. Total RNA was isolated from dissected tissues. Expression of miR-96-5p, miR-134-5p, 181b-5p, and miR-200b-3p was determined by real-time RT-qPCR method. The expression of miR-200b-3p was significantly higher in cancerous prostate: both in adenocarcinomatous glands and in the adjacent, apparently unaffected glands compared to BPH samples. The expression of miR-181b-5p was lower in in both prostate cancer tissues and adjacent tissue compared to BPH samples. Expression of miR-96-5p and miR-134-5p was lower in prostate cancer tissues compared to BPH. Levels of miR-96-5p, miR-134-5p, and 181b-5p negatively correlated with the Gleason score. Given further studies, miR-96-5p, miR-134-5p and especially miR-200b-3p and miR-181b-5p may differentiate BPH and PC.

• Benign prostate hyperplasia
• Laser capture microdissection
• Prostate cancer
• microRNA

• breast cancer
• cancer genomics
• cancer imaging
• lung cancer
• tumour heterogeneity
• computational biology and bioinformatics
• image processing
• machine learning

• Female
• Humans
• Breast Neoplasms/diagnostic imaging
• Breast Neoplasms/genetics
• Breast Neoplasms/mortality
• Deep Learning
• Gene Expression
• Genetic Heterogeneity
• Image Processing, Computer-Assisted/methods
• Lung Neoplasms/diagnostic imaging
• Lung Neoplasms/genetics
• Lung Neoplasms/mortality
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Survival Rate

Since its first discovery as part of the Rous sarcoma virus (RSV) genome, the c-SRC (SRC) proto-oncogene has been proved a key regulator of cancer development and progression, and thus it has been highlighted as an attractive target for anti-cancer therapeutic strategies. Though the exact mechanisms of its action are still not fully understood, SRC protein mediates crucial normal cell functions, such as cell development, proliferation and survival, and its dysregulation is considered as an oncogenic signature and a driving force for cancer initiation. In the present review, we present a flashback to the history of the Src research, while focusing on the most important milestones in the field. Moreover, we investigate the proposed regulatory mechanisms and molecules that mediate its action in order to designate putative therapeutic targets and useful prognostic and/or diagnostic tools. Furthermore, we present and discuss existing therapeutic approaches that are explored in clinical settings.

• Rous sarcoma virus
• Src oncogene
• cancer therapy
• carcinogenesis
• miRNAs

MicroRNAs (miRNAs) are promising biomarkers due to their structural stability and distinct expression profile in various cancers. We wanted to explore the miRNA expression in benign breast tissue and breast cancer subgroups in the Norwegian Women and Cancer study.

Specimens and histopathological data from study participants in Northern Norway diagnosed with breast cancer, and benign tissue from breast reduction surgery were collected. Main molecular subtypes were based on surrogate markers; luminal A (ER+ and/or PR+, HER2− and Ki67 ≤ 30%), luminal B (ER+ and/or PR+, HER2− and Ki67 > 30% or ER+ and/or PR+ and HER2+), HER2 positive (ER− and PR− and HER2+) and triple-negative (ER−, PR− and HER2−). RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue, and miRNAs were successfully analyzed in 102 cancers and 36 benign controls using the 7th generation miRCURY LNA microarray containing probes targeting all human miRNAs as annotated in miRBASE version 19.0. Validation with RT-qPCR was performed.

On average, 450 miRNAs were detected in each sample, and 304 miRNAs were significantly different between malignant and benign tissue. Subgroup analyses of cancer cases revealed 23 miRNAs significantly different between ER+ and ER− tumors, and 47 miRNAs different between tumors stratified according to grade. Significantly higher levels were found in high grade tumors for miR-17-5p (p = 0.006), miR-20a-5p (p = 0.007), miR-106b-5p (p = 0.007), miR-93-5p (p = 0.007) and miR-25-3p (p = 0.015) from the paralogous clusters miR-17-92 and miR-106b-25. Expression of miR-17-5p (p = 0.0029), miR-20a-5p (p = 0.0021), miR-92a-3p (p = 0.011) and miR-106b-5p (p = 0.021) was significantly higher in triple-negative tumors compared to the rest, and miR-17-5p and miR-20a-5p were significantly lower in luminal A tumors.

miRNA expression profiles were significantly different between malignant and benign tissue and between cancer subgroups according to ER− status, grade and molecular subtype. miRNAs in the miR-17-92 cluster and miR-17 family were overexpressed in high grade and triple-negative tumors associated with aggressive behavior. The expression and functional role of these miRNAs should be further studied in breast cancer to explore their potential as biomarkers in diagnostic pathology and clinical oncology.

• Breast cancer
• MicroRNA
• NOWAC
• miR-106b-25 cluster
• miR-17-92-cluster
• miR-17-family

Breast cancer, the most prevalent cancer type among women worldwide, remains incurable once metastatic. Long noncoding RNA (lncRNA) and microRNA (miRNA) play important roles in breast cancer by regulating specific genes or proteins. In this study, we found miR-133b was silenced in breast cancer cell lines and in breast cancer tissues, which predicted poor prognosis in breast cancer patients. We also confirmed that lncRNA NEAT1 was up-regulated in breast cancer and inhibited the expression of miR-133b, and identified the mitochondrial protein translocase of inner mitochondrial membrane 17 homolog A (TIMM17A) that serves as the target of miR-133b. Both miR-133b knockdown and TIMM17A overexpression in breast cancer cells promoted cell migration and invasion both in vitro and in vivo. In summary, our findings reveal that miR-133b plays a critical role in breast cancer cell metastasis by targeting TIMM17A. These findings may provide new insights into novel molecular therapeutic targets for breast cancer.

• NEAT1
• breast cancer
• metastasis
• miR-133b
• translocase of inner mitochondrial membrane 17 homolog A (TIMM17A)

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by suppressing the target mRNA and inhibiting translation in order to regulate multiple biological processes. miRNAs play important roles as oncogenes or tumor suppressors in the development of various types of human cancer. The regulation of mammalian target of rapamycin (mTOR) by miRNAs has been studied in several types of cancer, including colorectal cancer (CRC). However, to the best of our knowledge, only limited information regarding the function of miRNAs in human CRC is available. In the present study, the expression of 22 miRNAs in CRC cell lines were investigated in regard to key genes in the mTOR pathway. Initially, it was revealed that mTOR, regulatory-associated protein of mTOR complex I and rapamycin-intensive companion of mTOR were overexpressed in CRC cell lines when compared with a normal colorectal cell line. Subsequently, putative miRNA-mRNA associations were identified via multiple miRNA target prediction programs. The expression levels for the candidate miRNAs were validated using quantitative real-time polymerase chain reaction. Expression analysis revealed that, among 20 miRNAs, five miRNAs (miR-496, miR-1185, miR-654, miR-3183 and miR-495) exhibited significant downregulation in association with the mTOR signaling pathway. Taken together, the results from the present study suggest that several miRNAs that are associated with CRC, with possible roles in mTOR signaling, may have potential therapeutic or diagnostic benefits in CRC treatment.

• colorectal cancer
• mammalian target of rapamycin
• microRNA
• rapamycin-insensitive companion of mammalian target of rapamycin
• regulatory-associated protein of mammalian target of rapamycin complex 1

Lung cancer is a leading global cause of cancer‐related death, and lung adenocarcinoma (LUAD) accounts for ~ 50% of lung cancer. Here, we screened for novel and specific biomarkers of LUAD by searching for differentially expressed mRNAs (DEmRNAs) and microRNAs (DEmiRNAs) in LUAD patient expression data within The Cancer Genome Atlas (TCGA). The identified optimal diagnostic miRNA biomarkers were used to establish classification models (including support vector machine, decision tree, and random forest) to distinguish between LUAD and adjacent tissues. We then predicted the targets of identified optimal diagnostic miRNA biomarkers, functionally annotated these target genes, and performed receiver operating characteristic curve analysis of the respective DEmiRNA biomarkers, their target DEmRNAs, and combinations of DEmiRNA biomarkers. We validated the expression of selected DEmiRNA biomarkers by quantitative real‐time PCR (qRT‐PCR). In all, we identified a total of 13 DEmiRNAs, 2301 DEmRNAs and 232 DEmiRNA–target DEmRNA pairs between LUAD and adjacent tissues and selected nine DEmiRNAs (hsa‐mir‐486‐1, hsa‐mir‐486‐2, hsa‐mir‐153, hsa‐mir‐210, hsa‐mir‐9‐1, hsa‐mir‐9‐2, hsa‐mir‐9‐3, hsa‐mir‐577, and hsa‐mir‐4732) as optimal LUAD‐specific biomarkers with great diagnostic value. The predicted targets of these nine DEmiRNAs were significantly enriched in transcriptional misregulation in cancer and central carbon metabolism. Our qRT‐PCR results were generally consistent with our integrated analysis. In summary, our study identified nine DEmiRNAs that may serve as potential diagnostic biomarkers of LUAD. Functional annotation of their target DEmRNAs may provide information on their roles in LUAD.

• DEmiRNA
• LUAD
• TCGA
• biomarker
• lung adenocarcinoma
• microRNA

• 3' Untranslated Regions
• Adenomatous Polyposis Coli Protein/genetics
• Aged
• Antimetabolites, Antineoplastic/therapeutic use
• Ataxia Telangiectasia Mutated Proteins/genetics
• Binding Sites
• Case-Control Studies
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Female
• Fluorouracil/therapeutic use
• Genetic Predisposition to Disease
• Humans
• Male
• MicroRNAs/metabolism
• Middle Aged
• Poly (ADP-Ribose) Polymerase-1/genetics
• Poly (ADP-Ribose) Polymerase-1/metabolism
• Polymorphism, Single Nucleotide
• Prognosis
• Proto-Oncogene Proteins p21(ras)/genetics
• RNA, Messenger/metabolism
• Smad7 Protein/genetics

• hepatic stellate cells
• microRNAs
• portal hypertension

Enhanced radiosensitivity at low doses of ionizing radiation (IR) (0.2 to 0.6 Gy) has been reported in several cell lines. This phenomenon, known as low doses hyper-radiosensitivity (LDHRS), appears as an opportunity to decrease toxicity of radiotherapy and to enhance the effects of chemotherapy. However, the effect of low single doses IR on cell death is subtle and the mechanism underlying LDHRS has not been clearly explained, limiting the utility of LDHRS for clinical applications. To understand the mechanisms responsible for cell death induced by low-dose IR, LDHRS was evaluated in DLD-1 human colorectal cancer cells and the expression of 80 microRNAs (miRNAs) was assessed by qPCR array. Our results show that DLD-1 cells display an early DNA damage response and apoptotic cell death when exposed to 0.6 Gy. miRNA expression profiling identified 3 over-expressed (miR-205-3p, miR-1 and miR-133b) and 2 down-regulated miRNAs (miR-122-5p, and miR-134-5p) upon exposure to 0.6 Gy. This miRNA profile differed from the one in cells exposed to high-dose IR (12 Gy), supporting a distinct low-dose radiation-induced cell death mechanism. Expression of a mimetic miR-205-3p, the most overexpressed miRNA in cells exposed to 0.6 Gy, induced apoptotic cell death and, more importantly, increased LDHRS in DLD-1 cells. Thus, we propose miR-205-3p as a potential radiosensitizer to low-dose IR.

• low-dose ionizing radiation
• miR-205-3p
• miRNA
• radiosensitivity

MicroRNAs, a family of single-stranded and non-coding RNAs, play a crucial role in regulating gene expression at posttranscriptional level, by which it can mediate various types of physiological and pathological process in normal developmental progress and human disease, including cancer. The microRNA-133b originally defined as canonical muscle-specific microRNAs considering their function to the development and health of mammalian skeletal and cardiac muscles, but new findings coming from our group and others revealed that miR-133b have frequently abnormal expression in various kinds of human cancer and its complex complicated regulatory networks affects the tumorigenicity and development of malignant tumors. Very few existing reviews on miR-133b, until now, are principally about its role in homologous cluster (miR-1, −133 and -206s), however, most of constantly emerging new researches now are focused mainly on one of them, so In this article, to highlight the unique pathological role of miR-133b playing in tumor, we conduct a review to summarize the current understanding about one of the muscle-specific microRNAs, namely miR-133b, acting in human cancer. The review focused on the following four aspects: the overview of miR-133b, the target genes of miR-133b involved in human cancer, the expression of miR-133b and regulatory mechanisms leading to abnormal expression of miR-133b.

• cancer
• miR-133b
• microRNAs
• myomiRs
• tumor

It is reported that miRNAs are aberrantly expressed in patients with pancreatic cancer. However, the diagnostic value of miRNAs in pancreatic cancer remains controversial. The meta-analysis was to access diagnostic accuracy of miRNAs in pancreatic cancer.

PubMed, Scopus, Web of Science, Chinese National Knowledge Infrastructure (CNKI), WANFANG Data, China Biomedical Literature Database (CBM), and VIP databases were retrieved up to June 30, 2016, to collect articles concerning the diagnosis of miRNAs in pancreatic cancer. The methodological quality of each study was assessed by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). This meta-analysis was conducted using RevMan5.0, MetaDiSc 1.4, and Stata 12.0 software.

There are 40 articles including 109 studies. The pooled SEN was 0.81 (95% CI, 0.80–0.82), the pooled SPE was 0.78 (95% CI, 0.77–0.79), the pooled +LR was 3.32 (95% CI, 2.92–3.80), the pooled −LR was 0.27 (95% CI, 0.24–0.31), the pooled DOR was 14.56 (95% CI, 11.55–18.34), and pooled AUC was 0.86 (95% CI, 0.84–0.88).

This meta-analysis demonstrated that miRNA makes a significant impact in the pancreatic cancer diagnosis with a high SEN and SPE, particularly using multiple miRNAs.

• Carcinoma
• Early Detection of Cancer
• Endosonography
• Neoplasm Metastasis
• Neoplasms
• Pancreas
• Pancreatic Ductal
• Pancreatic Neoplasms
• Therapeutics

• UL1 TR001064 NCATS NIH HHS

The discovery of microRNAs (miRNAs) has opened up new avenues for studying cancer at the molecular level, featuring a post-genomic era of biomedical research. These non-coding regulatory RNA molecules of ~22 nucleotides have emerged as important cancer biomarkers, effectors, and targets. In this review, we focus on the dysregulated biogenesis and function of miRNAs in cancers with an overexpression of the proto-oncogene HER2. Many of the studies reviewed here were carried out in breast cancer, where HER2 overexpression has been extensively studied and HER2-targeted therapy practiced for more than a decade. MiRNA signatures that can be used to classify tumors with different HER2 status have been reported but little consensus can be established among various studies, emphasizing the needs for additional well-controlled profiling approaches and meta-analyses in large and well-balanced patient cohorts. We further discuss three aspects of microRNA dysregulation in or contribution to HER2-associated malignancies or therapies: (a) miRNAs that are up- or down-regulated by HER2 and mediate the downstream signaling of HER2; (b) miRNAs that suppress the expression of HER2 or a factor in HER2 receptor complexes, such as HER3; and (c) miRNAs that affect responses to anti-HER2 therapies. The regulatory mechanisms are elaborated using mainly examples of miR-205, miR-125, and miR-21. Understanding the regulation and function of miRNAs in HER2-overexpressing tumors shall shed new light on the pathogenic mechanisms of microRNAs and the HER2 proto-oncogene in cancer, as well as on individualized or combinatorial anti-HER2 therapies.

• breast cancer
• miR-181a
• miR-23a
• microRNA
• progesterone receptor

• Algorithms
• Computational Biology/methods
• Entropy
• Fuzzy Logic
• Gene Expression Profiling/methods
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neoplasms/genetics
• Neoplasms/metabolism
• Pattern Recognition, Automated

MicroRNAs (miRNAs) are short non-coding RNA molecules that play a significant role in many types of cancers including breast cancer. In the current study, we evaluated the expression levels of microR-10b (miR-10b) in 115 breast cancer patients from Sichuan Cancer Center. Real time reverse transcription-PCR was used to assess miR-10b expression. Clinical data including disease stage, survival status, age, ER/PR/HER2 status, molecular subtypes, tumor size, lymph node status and Ki-67 expression levels were correlated with miR-10b expression levels. Our data showed that the miR-10b expression is correlated with disease stage, living status and tumor sizes. We also found that miR-10b expression levels are higher in the lymph node positive group and the Ki-67 higher scoring group (score > 20). No statistically significant differences were observed based on age or molecular sub-type grouping. In conclusion, miR-10b may be a biomarker for breast cancer and is a potential treatment target.

• Breast Neoplasms/genetics
• Female
• Genes, erbB-2
• Humans
• MicroRNAs/genetics
• Middle Aged
• Real-Time Polymerase Chain Reaction
• Receptors, Estrogen/metabolism
• Receptors, Progesterone/metabolism
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Analysis

• the Program for provincial universities innovative research team in Sichuan province

• FOXP2 factor
• cancer
• language
• oncogene
• prognosis

• Breast cancer
• Ductal carcinoma in situ
• Lymphovascular invasion
• MicroRNA

• Adult
• Aged
• Axilla
• Blood Vessels/pathology
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Breast Neoplasms/pathology
• Breast Neoplasms/surgery
• Carcinoma, Ductal, Breast/genetics
• Carcinoma, Ductal, Breast/metabolism
• Carcinoma, Ductal, Breast/pathology
• Carcinoma, Ductal, Breast/surgery
• Carcinoma, Intraductal, Noninfiltrating/genetics
• Carcinoma, Intraductal, Noninfiltrating/metabolism
• Carcinoma, Intraductal, Noninfiltrating/pathology
• Carcinoma, Intraductal, Noninfiltrating/surgery
• Cell Line, Tumor
• Disease Progression
• Female
• Formaldehyde
• Gene Expression Profiling
• Humans
• Lymph Node Excision
• Lymph Nodes/metabolism
• Lymph Nodes/pathology
• Lymph Nodes/surgery
• Lymphatic Metastasis/genetics
• MicroRNAs/genetics
• Middle Aged
• Neoplasm Invasiveness/genetics
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• Paraffin Embedding
• Pilot Projects
• Reproducibility of Results
• Reverse Transcriptase Polymerase Chain Reaction

Micro RNA (miR)-486-5p is often aberrantly expressed in human cancers. The aim of this study was to identify the prognostic value of miR-486-5p expression in digestive system cancers. Tissue microarrays were constructed with 680 samples including 185 esophageal squamous cell carcinomas (ESCCs), 90 gastric adenocarcinomas (GCs), and 60 digestive system cancer tissues from 10 ESCC, 10 GC, 10 colon, 10 rectum, 10 liver, 10 pancreatic cancer, and corresponding normal tissues. Twenty normal digestive system mucosa tissues from healthy volunteers were included as normal controls. In GC, miR-486-5p expression was decreased in 62.8% of cases (59/94), increased in 33.0% (31/94), and unchanged in 4.2% (4/94); in ESCC its expression was decreased in 66.2% (129/195), increased in 32.3% (63/195), and unchanged in 1.5% (3/195). Expression of miR-486-5p was decreased in 12, and increased in 8, of 20 cases of colon or rectum cancer; decreased in 6, and increased in 4, of 10 cases of liver cancer; and decreased in 8, and increased in 2, of 10 cases of pancreatic cancer. Multivariate and univariate regression analysis demonstrated that low/unchanged miR-486-5p predicted poor prognosis in ESCC (hazard ratio [HR], 4.32; 95% confidence interval [CI], 2.62–7.14; P < 0.001; HR, 3.88; 95% CI, 2.43–6.22; P < 0.001, respectively) and GC (HR, 2.46; 95% CI, 1.35–4.50; P = 0.003; HR, 2.55; 95% CI, 1.39–4.69; P = 0.002, respectively). MiR-486-5p might therefore be an independent tumor marker for evaluating prognosis in patients with ESCC or GC.

• digestive system cancers
• esophageal squamous cell carcinoma
• gastric adenocarcinoma
• micro RNA-486-5p
• prognosis

• ANK1
• Epigenetics
• Intronic microRNA
• NSCLC
• miR-486-5p

• Adenocarcinoma/etiology
• Adenocarcinoma/genetics
• Adenocarcinoma/metabolism
• Adenocarcinoma/pathology
• Adenocarcinoma of Lung
• Ankyrins/genetics
• Ankyrins/metabolism
• Carcinoma, Non-Small-Cell Lung/etiology
• Carcinoma, Non-Small-Cell Lung/genetics
• Carcinoma, Non-Small-Cell Lung/metabolism
• Carcinoma, Non-Small-Cell Lung/pathology
• Carcinoma, Squamous Cell/etiology
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/pathology
• Cell Line, Tumor
• CpG Islands
• DNA Methylation
• Databases, Genetic
• Down-Regulation
• Epigenesis, Genetic
• Gene Expression Regulation, Neoplastic
• Humans
• Introns
• Lung Neoplasms/etiology
• Lung Neoplasms/genetics
• Lung Neoplasms/metabolism
• Lung Neoplasms/pathology
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Promoter Regions, Genetic
• Risk Factors
• Smoking/adverse effects

• R01 CA183296 NCI NIH HHS
• R01 CA193532 NCI NIH HHS
• R21 CA161561 NCI NIH HHS

• Biomarker
• Breast cancer
• MicroRNA
• Microarray

MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional regulators of gene expression and are dysregulated in cancer. Studies of miRNAs to explore their potential as diagnostic and prognostic markers are of great scientific interest. Here, we investigate the functional properties and expression of the miR-143/145 cluster in breast cancer (BC) in vitro and in vivo. The ER positive MCF7, the HER2 positive SK-BR-3, and the triple negative cell line MDA-MB-231 were used to assess cell proliferation and cell invasion. Expression of miRNA in 108 breast cancers in the Norwegian Women and Cancer Study and 44 benign tissue controls were analyzed by microarray and validated by RT-PCR. Further, in situ hybridization (ISH) was used to study the cellular and subcellular distribution of the miRNAs. In vitro, miR-143 promoted proliferation of MCF7 and MDA-MB-231 cells, whereas miR-145 and the cotransfection of both miRNAs inhibited proliferation in all three cell lines. The cells’ invasive capacity was reduced after transfection and cotransfection of the miRNAs. In line with the tumor suppressive functions in vitro, the expression of miR-143 and miR-145 was lower in malignant compared to benign breast tissue, and lower in the more aggressive tumors with higher tumor grade, loss of ER and the basal-like phenotype. ISH revealed miR-143 to be cytoplasmatic and predominantly expressed in luminal cells in benign tissue, whilst miR-145 was nuclear and with strong staining in myoepithelial cells. Both miRNAs were present in malignant epithelial cells and stromal fibroblasts in BC. This study demonstrates that miR-143 and -145 have functional properties and expression patterns typical for tumor suppressors, but the function is influenced by cellular factors such as cell type and miRNA cotransfection. Further, the nuclear functions of miR-145 should be explored for a more complete understanding of the complexity of miRNA regulation and function in BC.

• Breast Neoplasms/genetics
• Breast Neoplasms/pathology
• Cell Line, Tumor
• Female
• Humans
• In Situ Hybridization
• MicroRNAs/genetics
• Multigene Family
• Oligonucleotide Array Sequence Analysis

• Cancer
• Fuzzy mutual information
• Gene expression
• Pattern recognition
• Soft computing
• miRNA expression

• lung cancer
• miR-133b
• miR-206
• miR-206/133b cluster

In our previous studies, the Illumine Soledad massively parallel signature sequencing of miRNomes in non-tumor and hepatocellular carcinoma (HCC) tissues revealed that microRNA (miR)-144-3p was significantly downregulated in HCC, but its role in HCC development, especially angiogenesis, remains unclear. In this investigation, we found recovering miR-144-3p expression can significantly suppress the growth, migration and induced angiogenic capacity of HCC cells through both in vivo and in vitro experiments. Moreover, clinical correlation analysis showed that low expression of miR-144-3p was positively correlated to poor disease-free survival (DFS) of HCC patients. Mechanistically, serum and glucocorticoid kinase 3 (SGK3), the putative targets of miR-144-3p, was predicted by Target Scan database and identified to be suppressed by miR-144-3p so that inhibiting the activation of mTOR-VEGF downstream signals was activated by the phosphoinositide 3-kinase (PI3K)-independent pathway. Hence, we concluded that miR-144-3p, which is frequently downregulated in HCC, can inhibit proliferation, migration and repress angiogenesis by regulating SGK3 activation with PI3K independent signal pathway, and acts as a prognostic factor for HCC patients.

• Cell proliferation
• FZD7
• Oral squamous cell carcinoma
• Wnt signaling pathway
• miR-27b

Different breast cancer subtypes show distinct tropisms for sites of metastasis. Notably, the lung is the most common site for the first distant recurrence in triple-negative breast cancer (TNBC). The identification of novel biomarkers for lung metastasis is of great importance to improving the outcome of TNBC. In this study, we sought to identify a microRNA (miRNA)-based biomarker and therapeutic target for lung metastasis of TNBC.

A total of 669 patients without de novo stage IV TNBC were recruited for this study. miRNA profiling was conducted in the discovery cohort. Diagnostic accuracy and prognostic values of candidate miRNAs were evaluated in the training and validation cohorts, respectively. The biological functions of candidate miRNAs, as well as potential targets, were further evaluated through bioinformatic analysis as well as by performing in vitro and in vivo assays.

In the discovery set, we found that miR-629-3p was specifically upregulated in both metastatic foci (fold change 144.16, P < 0.0001) and primary tumors (fold change 74.37, P = 0.004) in patients with lung metastases. In the training set, the ROC curve showed that miR-629-3p yielded high diagnostic accuracy in discriminating patients with lung metastasis from patients without recurrence (AUC 0.865, 95% CI 0.800–0.930, P < 0.0001). Although miR-629-3p predicted poor overall survival and disease-free survival in the validation set, it failed to show significance after multivariate analysis. Notably, logistic regression analyses confirmed that miR-629-3p was an independent risk factor for lung metastasis (OR 4.1, 95% CI 2.5–6.6, P < 0.001). Inhibition of miR-629-3p drastically attenuated the viability and migration of TNBC cells, and it markedly suppressed lung metastasis in vivo. Furthermore, we identified the leukemia inhibitory factor receptor (LIFR), a well-known metastatic suppressive gene, to be a direct target of miR-629-3p.

miR-629-3p may serve as a novel biomarker and potential therapeutic target for lung metastases of TNBC mediated via LIFR.

The online version of this article (doi:10.1186/s13058-017-0865-y) contains supplementary material, which is available to authorized users.

• Biomarker
• LIFR
• Lung metastasis
• Triple-negative breast cancer
• miR-629-3p

• Aortic dilation
• Bicuspid aortic valve
• microRNA

• SROC
• diagnostics
• meta-analysis
• multiple miRNA
• pancreatic cancer

• Biomarkers, Tumor/blood
• Biomarkers, Tumor/genetics
• Case-Control Studies
• Humans
• MicroRNAs/blood
• MicroRNAs/genetics
• Pancreatic Neoplasms/blood
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• Prognosis

• Gene Expression
• Polymorphism, Single Nucleotide
• Quantitative Trait Loci
• RNA, Messenger/genetics

• R01 HL113264 NHLBI NIH HHS
• R01 HL094635 NHLBI NIH HHS
• R01 HL089856 NHLBI NIH HHS
• R01 NR013377 NINR NIH HHS
• P01 HL105339 NHLBI NIH HHS
• R01 HL126596 NHLBI NIH HHS
• R21 HG007687 NHGRI NIH HHS
• R01 HL124233 NHLBI NIH HHS
• R01 HL125583 NHLBI NIH HHS
• National Human Genome Research Institute
• National Heart, Lung, and Blood Institute
• National Institutes of Health
• National Institute of Nursing Research

• CLTA
• Endocytosis
• Perfluorooctanoic acid
• miRNA