• biomarkers
• laryngeal carcinoma
• microRNA
• prognosis
• survival

• Humans
• MicroRNAs/genetics
• Biomarkers, Tumor/genetics
• Laryngeal Neoplasms/genetics
• Laryngeal Neoplasms/diagnosis
• Laryngeal Neoplasms/pathology
• Prognosis
• Gene Expression Regulation, Neoplastic
• Signal Transduction/genetics

• BG-RRP-2.004-0004-C01", group 3.1.5 European Union

• External beam radiation
• Prostate cancer
• Radioresistance
• RhoC
• Xenograft mouse model

• Male
• Animals
• Prostatic Neoplasms/radiotherapy
• Prostatic Neoplasms/metabolism
• Prostatic Neoplasms/pathology
• Prostatic Neoplasms/genetics
• Ki-67 Antigen/metabolism
• Ki-67 Antigen/genetics
• Humans
• rhoC GTP-Binding Protein/metabolism
• rhoC GTP-Binding Protein/genetics
• Mice
• Mice, Inbred BALB C
• Neoplasm Recurrence, Local/metabolism
• Cell Line, Tumor
• Mice, Nude
• rho GTP-Binding Proteins/metabolism
• rho GTP-Binding Proteins/genetics

• Biomarker
• Cancer
• Drug resistance
• miRNA-93

Background: Long non-coding RNAs modulate tumor occurrence through different molecular mechanisms. It had been reported that HNF1A-AS1 (HNF1A Antisense RNA 1) was differently expressed in multiple tumors. The role of HNF1A-AS1 in colorectal cancer was less analyzed, and the mechanism of regulating the cell cycle has not been completely elucidated. Methods: Differentially expressed lncRNAs were screened out from the TCGA database. HNF1A-AS1 was examined in CRC clinical samples and cell lines by RT-qPCR. CCK8 assay, colony formation assay, flow cytometry, transwell assays, tube forming assay and vivo experiments were performed to study the function of HNF1A-AS1 in CRC tumor progression. Bioinformatic analysis, luciferase report assay, RNA pull-down and RIP assays were carried out to explore proteins binding HNF1A-AS1 and the potential downstream targets. Results: Our results showed that HNF1A-AS1 was upregulated in CRC and associated with unfavorable prognosis. HNF1A-AS1 promoted proliferation, migration and angiogenesis, accelerated cell cycle and reduced cell apoptosis in CRC. Bioinformatics prediction and further experiments proved that HNF1A-AS1 could promote CCND1 expression by suppressing PDCD4 or competitively sponging miR-93-5p. Meanwhile, METTL3 mediated HNF1A-AS1 m⁶A modification and affected its RNA stability. HNF1A-AS1/IGF2BP2/CCND1 may act as a complex to regulate the stability of CCND1. Conclusion: In summary, our result reveals the novel mechanism in which m⁶A-mediated HNF1A-AS1/IGF2BP2/CCND1 axis promotes CRC cell cycle progression, along with competitively sponging miR-93-5p to upregulate CCND1, demonstrating its significant role in cell cycle regulation and suggesting that HNF1A-AS1 may act as a potential prognostic marker of colorectal cancer in the future.

• The National Natural Science Foundation of China
• Natural Science Foundation of Guangdong Province

The androgen receptor (AR) is a member of the steroid hormone receptor family of nuclear transcription factors. It is present in the primary/secondary sexual organs, kidneys, skeletal muscles, adrenal glands, skin, nervous system, and breast. Abnormal AR functioning has been identified in numerous diseases, specifically in prostate cancer (PCa). Interestingly, recent studies have indicated a relationship between the AR and microRNA (miRNA) crosstalk and cancer progression. MiRNAs are small, endogenous, non-coding molecules that are involved in crucial cellular processes, such as proliferation, apoptosis, or differentiation. On the one hand, AR may be responsible for the downregulation or upregulation of specific miRNA, while on the other hand, AR is often a target of miRNAs due to their regulatory function on AR gene expression. A deeper understanding of the AR–miRNA interactions may contribute to the development of better diagnostic tools as well as to providing new therapeutic approaches. While most studies usually focus on the role of miRNAs and AR in PCa, in this review, we go beyond PCa and provide insight into the most recent discoveries about the interplay between AR and miRNAs, as well as about other AR-associated and AR-independent diseases.

• androgen receptor
• breast cancer
• cancer
• microRNA
• prostate cancer

Recently, over-expression of LAIR-1 has been found in some solid cancers, including ovarian cancer. The role of LAIR-1 in cancer progression needs further investigation. In this study, we identified the LAIR-1 cDNA sequence of the ovarian cancer cells HO8910. Using SKOV3 cells, we confirmed the finding from our previous study that LAIR-1 could suppress in vitro cell proliferation and cell migration. We also found LAIR-1 overexpression can induce apoptosis of SKOV3 cells. We revealed LAIR-1 suppressed cell growth by inhibiting the PI3K-AKT-mTOR axis. Moreover, the LAIR-1 antitumor activity and its mechanism were also identified in vivo. We used Co-IP assay and mass spectrometry to identify potential LAIR-1-binding proteins in LAIR-1 overexpressing SKOV3 cells. MS analysis identified 167 potentially interacting proteins. GO analyses indicated a possible involvement of LAIR-1 in mRNA processing through its interaction with some eukaryotic translation initiation factors (eIF4E1B, eIF2S3, eIF3D, eIF4G2, eIF5B) and eukaryotic translation elongation factors (eEF1A2 and eEF1B2). Our findings suggest that LAIR-1 may suppress the growth of ovarian cancer cells by serving as a modulator that suppresses PI3K-AKT-mTOR directly or regulating protein synthesis at the translational level. Our results indicate that a LAIR-1-based strategy may prevent or suppress the progression of ovarian cancer.

• LAIR-1
• PI3K-AKT-mTOR pathway
• cell proliferation
• eEF1A2
• ovarian cancer

• Cell function
• Melanoma
• TCEAL7
• Tumorigenesis
• miR-758-3p

• cell migration
• epithelial–mesenchymal transition
• metastasis
• miRNA
• oncomiR
• tumor invasiveness
• tumor suppressor miR

• Adenocarcinoma, Clear Cell/genetics
• Adenocarcinoma, Clear Cell/pathology
• Cell Line, Tumor
• Down-Regulation
• Female
• Humans
• Logistic Models
• Lymphatic Vessels/metabolism
• Lymphatic Vessels/pathology
• Machine Learning
• MicroRNAs/metabolism
• Neoplasm Recurrence, Local
• Neoplasm Staging
• Ovarian Neoplasms/genetics
• Ovarian Neoplasms/pathology
• Principal Component Analysis
• Prognosis
• Risk

• U01 HL123420 NHLBI NIH HHS
• Department of Health
• National Institutes of Health

Gastric cancer (GC) is one of the most prevalent cancers and a major cause of cancer related mortality worldwide. Incidence of GC is affected by various factors, including genetic and environmental factors. Despite extensive research has been done for molecular characterization of GC, it remains largely unknown. Therefore, further studies specially conducted among various ethnicities in different geographic locations, are required to know the precise molecular mechanisms leading to tumorigenesis and progression of GC. The expression patterns of seven candidate genes, including β-catenin, Notch1, GATA6, CDX2, miR-34a, miR-181a, and miR-93 were determined in 24 paired GC tissues and corresponding non-cancerous tissues by quantitative Real-Time PCR. The association between the expression of these genes and clinicopathologic factors were also investigated. Our results demonstrated that overall mRNA levels of GATA6 were significantly decreased in the tumor samples in comparison with the non-cancerous tissues (median fold change (FC) = 0.3143; P = 0.0003). Overall miR-93 levels were significantly increased in the tumor samples relative to the non-cancerous gastric tissues (FC = 2.441; P = 0.0002). β-catenin mRNA expression showed a strong positive correlation with miR-34a (r = 0.5784; P = 0.0031), and miR-181a (r = 0.5652; P = 0.004) expression. miR-34a and miR-181a expression showed a significant positive correlation (r = 0.4862; P = 0.016). Moreover, lower expression of Notch1 was related to distant metastasis in GC patients with a borderline statistical significance (p = 0.0549). These data may advance our understanding of the molecular biology that drives GC as well as provide potential targets for defining novel therapeutic strategies for GC treatment.

• Cancer therapy
• MicroRNA
• Oncogenesis
• Oncosuppressor
• Signaling pathway

• Rho GTPases
• biomarker-set
• breast cancer
• cervical cancer
• endometrial cancer
• function
• gynecologic oncology
• healing
• impairments
• in-depth diagnostics
• inflammation
• metastatic disease
• molecular cellular tissue level
• ovarian cancers
• paradigm change
• patient stratification
• predictive preventive personalized medicine (PPPM/3PM)
• prognosis
• regulation
• signaling pathways
• structure
• therapy resistance
• tumorigenesis

• ATP-binding cassette subfamily B member 1 gene (ABCB1)
• collagen type III alpha 1 chain gene (COL3A1)
• drug resistance
• microRNA
• ovarian cancer

• ATP Binding Cassette Transporter, Subfamily B/genetics
• Cell Line, Tumor
• Collagen Type III/genetics
• Drug Resistance, Neoplasm/genetics
• Extracellular Matrix/metabolism
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Humans
• MicroRNAs/genetics
• Ovarian Neoplasms/genetics
• Ovarian Neoplasms/metabolism
• Ovarian Neoplasms/pathology
• Transcriptome

• apoptosis
• chemoresistance
• clinical trials
• glycosylation
• miRNA
• ovarian cancer

Long non-coding RNAs (lncRNAs) have been shown to contribute to progression and prognosis of hepatocellular carcinoma (HCC). However, expression profiling and interaction of lncRNAs with messenger RNAs (mRNAs) and microRNAs (miRNAs) remain largely unknown in HCC. The expression profiling of lncRNAs, mRNA and miRNAs was obtained using microarray. The Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to characterize potential functions of differentially expressed mRNAs. Cytoscape was applied to construct an lncRNA-miRNA-mRNA co-expression network and candidate lncRNAs were validated via quantitative PCR in 30 pairs of HCC and adjacent tumor-free tissues. In this study, 1,056 upregulated and 1,288 downregulated lncRNAs were identified, while 2,687 mRNAs and 6 miRNAs were aberrantly expressed in HCC compared with adjacent tumor-free tissues. Potential functions of differentially expressed mRNAs were demonstrated to significantly participate in modulating critical genes in the cell cycle, such as cyclin E1 and cyclin B2. After screening, 95 lncRNAs, 5 miRNAs and 36 mRNAs were recruited for construction of lncRNA-mRNA-miRNA co-expression network in the cell cycle pathway. Subsequently, the top 5 lncRNAs that potentially modulate critical genes in the cell cycle were selected as the candidates for further verification. Kaplan-Meier curves using the Cancer Genome Atlas database showed that 13 targeted mRNAs were associated with overall survival of HCC patients. Finally, three lncRNAs, including ENST00000522221, lnc-HACE1-6:1 and lnc-ICOSLG-11:1, are significantly upregulated in HCC tissues compared with adjacent tumor-free tissues. These findings suggest that lncRNAs play essential roles in the pathogenesis of HCC via regulating coding genes and miRNAs, and may be important targets for diagnosis and treatment of this disease.

Tumor heterogeneity results in differential response to therapy due to the existence of plastic tumor cells, called cancer stem cells (CSCs), which exhibit the property of resistance to therapy, invasion and metastasis. These cells have a distinct, signaling network active at every stage of progression. It is difficult to envisage that the CSCs will have a unique set of signaling pathways regulating every stage of disease progression. Rather, it would be easier to believe that a single pivotal pathway having significant contribution at every stage, which can further turn on a battery of signaling mechanisms specific to that stage, would be instrumental in regulating the signaling network, enabling easy transition from one state to another. In this context, we discuss the role of RhoC which has contributed to several phenotypes during tumor progression.

RhoC (Ras homolog gene family member C) has been widely reported to regulate actin organization. It has been shown to impact the motility of cancer cells, resultantly affecting invasion and metastasis, and has contributed to carcinoma progression of the breast, pancreas, lung, ovaries and cervix, among several others. The most interesting finding has been its indispensable role in metastasis. Also, it has the ability to modulate various other phenotypes like angiogenesis, motility, invasion, metastasis, and anoikis resistance. These observations suggest that RhoC imparts the plasticity required by tumor cells to exhibit such diverse functions based on microenvironmental cues. This was further confirmed by recent reports which show that it regulates cancer stem cells in breast, ovary and head and neck cancers. Studies also suggest that the inhibition of RhoC results in abolition of advanced tumor phenotypes.

Our review throws light on how RhoC, which is capable of modulating various phenotypes may be the apt core signaling candidate regulating disease progression. Additionally, mice studies show that RhoC is not essential for embryogenesis, giving scope for its development as a possible therapeutic target. This review thus stresses on the need to understand the protein and its functioning in greater detail to enable its development as a stem cell marker and a possible therapeutic target.

• Cancer stem cells
• RhoC
• Therapy resistance
• Tumor phenotypes

• ALG-1
• Caenorhabditis elegans
• alternative splicing
• asd-2
• body muscle
• hrp-2
• intestine
• miRNA
• smu-2
• transcriptome

• Alternative Splicing
• Animals
• Caenorhabditis elegans
• Caenorhabditis elegans Proteins/genetics
• Caenorhabditis elegans Proteins/metabolism
• Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics
• Heterogeneous-Nuclear Ribonucleoprotein Group A-B/metabolism
• Intestinal Mucosa/metabolism
• Intracellular Signaling Peptides and Proteins/genetics
• Intracellular Signaling Peptides and Proteins/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Muscle, Skeletal/metabolism
• Organ Specificity
• RNA Splicing Factors/genetics
• RNA Splicing Factors/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• RNA-Binding Proteins/genetics
• RNA-Binding Proteins/metabolism

• R01 GM118796 NIGMS NIH HHS

Previous studies have shown that miR-373 functions as either a tumor suppressor or an oncogene depending on which type of cancer it’s operating in. However, the functional role of miR-373 in neuroblastoma (NB) remains largely unclear. 

Expression of miR-373 and SRC kinase signaling inhibitor 1 (SRCIN1) in 20 metastatic and 20 primary NB tissues was detected by quantitative real-time PCR (qRT-PCR) and Western blotting. MTT assay, flow cytometry analysis and transwell migration and invasion assays were performed to evaluate the influence of miR-373 inhibition on the growth, migration and invasion of NB cells, respectively. In vivo experiment was applied to determine the effect of miR-373 inhibition on tumor growth. Dual-luciferase reporter assay was used to confirm the interaction between miR-373 and SRCIN1.

We observed a significant increase in the expression of miR-373 in metastatic NB samples compared with primary NB samples, and this was inversely correlated with SRCIN1 expression. Functional studies revealed that depletion of miR-373 inhibited in vitro NB cell growth, migration and invasion, and also suppressed tumor growth in an in vivo mouse model. Moreover, we identified that SRCIN1 was a direct and functional target gene of miR-373. Silencing of SRCIN1 partially rescued the antimiR-373-mediated inhibition of cell growth, migration and invasion.

The data from our study verified a potential oncogenic role of miR-373 in NB cells that occurs through direct targeting SRCIN1. The newly identified miR-373/SRCIN1 axis represents a new potential candidate for therapeutic intervention of malignant NB.

• NB
• SRCIN1
• growth
• invasion
• miR-373
• migration

Exosomes are nanovesicles secreted from various types of cells and can be isolated from various bodily fluids, such as blood and urine. The number and molecular contents, including proteins and RNA of exosomes, have been shown to reflect their parental cell origins, characteristics and biological behaviors. An increasing number of studies have demonstrated that exosomes play a role in the course of tumorigenesis, diagnosis, treatment and prognosis, although its precise functions in tumors are still unclear. Moreover, owing to a lack of a standard approach, exosomes and its contents have not yet been put into clinical practice successfully. This review aims to summarize the current knowledge on exosomes and its contents in esophageal cancer as well as the current limitations/challenges in its clinical application, which may provide a basis for an all-around understanding of the implementation of exosomes and exosomal contents in the surveillance and therapy of esophageal cancer.

• Exosome
• Esophageal cancer
• Tumorigenesis
• Biomarker
• Therapeutic potential

• CDK14
• Epithelial ovarian cancer
• Invasion
• Proliferation
• miR-542-3p

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

• Gene Ontology
• diagnosis
• meta-analysis
• microRNA-93
• prognosis
• quantitative polymerase chain reaction

Specific microRNAs (miRNAs) are packaged in exosomes that regulate processes in tumor development and progression. The current study focuses on the influence of exosomal miRNAs in the pathogenesis of epithelial ovarian cancer (EOC). MiRNA profiles were determined in exosomes from plasma of 106 EOC patients, eight ovarian cystadenoma patients, and 29 healthy women by TaqMan real‐time PCR‐based miRNA array cards containing 48 different miRNAs. In cell culture experiments, the impact of miR‐200b and miR‐320 was determined on proliferation and apoptosis of ovarian cancer cell lines. We report that miR‐21 (P = 0.0001), miR‐100 (P = 0.034), miR‐200b (P = 0.008), and miR‐320 (P = 0.034) are significantly enriched, whereas miR‐16 (P = 0.009), miR‐93 (P = 0.014), miR‐126 (P = 0.012), and miR‐223 (P = 0.029) are underrepresented in exosomes from plasma of EOC patients as compared to those of healthy women. The levels of exosomal miR‐23a (P = 0.009, 0.008) and miR‐92a (P = 009, 0.034) were lower in ovarian cystadenoma patients than in EOC patients and healthy women, respectively. The exosomal levels of miR‐200b correlated with the tumor marker CA125 (P = 0.002) and patient overall survival (P = 0.019). MiR‐200b influenced cell proliferation (P = 0.0001) and apoptosis (P < 0.008). Our findings reveal specific exosomal miRNA patterns in EOC and ovarian cystadenoma patients, which are indicative of a role of these miRNAs in the pathogenesis of EOC.

• apoptosis
• cell proliferation
• epithelial ovarian cancer
• exosomes
• ovarian cystadenoma
• prognosis

• metabolism
• ovarian cancer
• statins
• stemness
• therapy

• Cell Line, Tumor
• Cell Movement/drug effects
• Cell Plasticity/drug effects
• Epithelial-Mesenchymal Transition/drug effects
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
• Neoplasm Metastasis/pathology
• Neoplastic Stem Cells/drug effects
• Neoplastic Stem Cells/pathology
• Ovarian Neoplasms/pathology
• Simvastatin/pharmacology

Lacrimal adenoid cystic carcinoma (LACC) is one of the most common malignancies that affects lacrimal gland. MicroRNAs are known to play a crucial role as oncogenes or tumor suppressors. Specifically, miR-93 has been reported to play a crucial role in colorectal, breast, pancreatic, lung cancer and hepatocellular carcinoma. However, the role of miR-93 in LACC and the potential molecular mechanisms involved remain unknown. Therefore, we took the challenge to determine the involvement of miR-93 in the LACC by targeting BRMS1L.

A total of 5 adenoid cystic carcinoma (ACC) of lacrimal gland patient tissues and their plasma were examined. Three normal lacrimal glands and three normal serums were collected as a control group. After surgical resection, the specimens were preserved in liquid nitrogen and stored at − 80 °C until RNA extraction. Afterwards, LACC cells with miR-93-5p overexpression were subjected to qRT-PCR and western blot for epithelial–mesenchymal transition (EMT) markers levels. Ability of LACC cell migration, invasion, proliferation and apoptosis was examined by wounded healing, transwell, CCK-8 and apoptosis assays. Afterwards, TargetScan was used to predict putative targets of miR-93-5p. Then, the examination was performed whether miR-93-5p targets BRMS1L by the use of luciferase reporter assays and western blotting. Finally, immunohistochemical staining was sone and all the images were taken using a microscope (Nikon, Tokyo).

Our results showed that miR-93 was overexpressed in tissues and plasma of LACC patients compared to healthy controls. MiR-93 downregulated E-cadherin expression while increasing N-cadherin expression and significantly inhibited luciferase activity. Furthermore, western blotting results confirmed that miR-93-5p could inhibit BRMS1L expression. The BRMS1L staining in LACC tissues was weaker than in normal controls. In addition, miR-93-5p revealed a reverse correlation with the expression of BRMS1L. In addition, significant upregulation of E-cadherin and downregulation of N-cadherin were found when LACC cells were transfected with BRMS1L. Finally, miR-93-5p significantly enhanced TOP/FOP luciferase activity. Upregulation of BRMS1L reduced TOP/FOP luciferase activity while further overexpression of miR-93-5p could not rescue Wnt signaling activity.

Our findings report that miR-93 promotes LACC cell migration, invasion, and proliferation via targeting downregulation of BRMS1L through regulation of Wnt signaling pathway.

The online version of this article (10.1186/s12935-018-0552-9) contains supplementary material, which is available to authorized users.

• Adenoid cystic carcinoma
• BRMS1L
• Lacrimal gland
• Plasma
• Tissue
• Tumorigenesis
• miR-93-5p

Ovarian cancer is among the leading cause of cancer-related deaths in females. In this study, we demonstrated that miR-595 expression was downregulated in the ovarian cancer tissues and cell lines. miR-595 expression was lower in the lymph node metastases tissues than in the primary ovarian cancer tissues and normal tissues. Furthermore, miR-595 overexpression suppressed the ovarian cancer cell proliferation, colony formation and invasion and promoted the sensitivity of ovarian cancer cell to cisplatin. We identified ABCB1 as a direct target gene of miR-595 in the ovarian cancer cell. ABCB1 expression was upregulated in the ovarian cancer tissues and cell lines. Morevoer, the expression level of ABCB1 was inversely correlated with miR-595 in the ovarian cancer tissues. In addition, overexpression of ABCB1 decreased the miR-595-overexpressing HO8910PM and SKOV-3 cell sensitivity to cisplatin. Ectopic expression of ABCB1 promoted the miR-595-overexpressing HO8910PM and SKOV-3 cell proliferation, colony formation and invasion. These data suggested that miR-595 acted a tumor suppressor role in ovarian cancer development and increased the sensitivity of ovarian cancer to cisplatin.

• ABCB1
• miR-595
• microRNAs
• ovarian cancer

MicroRNAs (miRNAs) are important regulators of pathobiological processes in various cancer. In the present study, we demonstrated that miR-93 expression was significantly up-regulated in gastric cancer tissues compared with that in matched normal mucosal tissues. High expression of miR-93 was significantly associated with lymph node metastasis and tumor-node-metastasis (TNM) stage. Functionally, ectopic expression of miR-93 promoted cell proliferation, migration, invasion, EMT phenotypes, and repressed apoptosis and G1 cell cycle arrest in vitro, and promoted tumor formation in vivo. We further identified that tissue inhibitor of metalloproteinase 2 (TIMP2) was a direct target of miR-93 by using luciferase reporter assay, qRT-PCR, and immunoblotting assay. Furthermore, knockdown of TIMP2 with specific siRNA showed similar oncogenic effects in gastric cancer cells with that transfected with miR-93 mimics. Our findings indicated that miR-93 serves as a tumor promoter in human gastric carcinogenesis by targeting TIMP2, suggesting that miR-93 might be a promising biomarker and therapeutic target for treatment of gastric cancer.

• Humans
• Lymphatic Metastasis
• MicroRNAs/physiology
• Neoplasm Metastasis
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology
• Tissue Inhibitor of Metalloproteinase-2/metabolism

• National Natural Science Foundation of China (CN)

• CDKN1A
• microRNA-93
• nasopharyngeal carcinoma
• proliferation

• epithelial ovarian carcinoma
• lncRNA TDRG1
• progression miR-93
• tumorigenesis

• Gastric cancer
• IFNAR1
• Metastasis
• STAT3
• miR-93-5p

• Epithelial ovarian cancer
• RhoC
• Tumor
• Tumorigenesis and progression
• lncRNA ABHD11-AS1

Supplemental Digital Content is available in the text

The aim of our study was to analyze the miRNome of pancreatic ductal adenocarcinoma (PDAC) and its preneoplastic lesion intraductal papillary mucinous neoplasm (IPMN), to find new microRNA (miRNA)-based biomarkers for early detection of pancreatic neoplasia.

Effective early detection methods for PDAC are needed. miRNAs are good biomarker candidates.

Pancreatic tissues (n = 165) were obtained from patients with PDAC, IPMN, or from control individuals (C), from Hospital Clínic of Barcelona. Biomarker discovery was done using next-generation sequencing in a discovery set of 18 surgical samples (11 PDAC, 4 IPMN, 3 C). MiRNA validation was carried out by quantitative reverse transcriptase PCR in 2 different set of samples. Set 1—52 surgical samples (24 PDAC, 7 IPMN, 6 chronic pancreatitis, 15 C), and set 2—95 endoscopic ultrasound-guided fine-needle aspirations (60 PDAC, 9 IPMN, 26 C).

In all, 607 and 396 miRNAs were significantly deregulated in PDAC and IPMN versus C. Of them, 40 miRNAs commonly overexpressed in both PDAC and IPMN were selected for further validation. Among them, significant up-regulation of 31 and 30 miRNAs was confirmed by quantitative reverse transcriptase PCR in samples from set 1 and set 2, respectively.

miRNome analysis shows that PDAC and IPMN have differential miRNA profiles with respect to C, with a large number of deregulated miRNAs shared by both neoplastic lesions. Indeed, we have identified and validated 30 miRNAs whose expression is significantly increased in PDAC and IPMN lesions. The feasibility of detecting these miRNAs in endoscopic ultrasound-guided fine-needle aspiration samples makes them good biomarker candidates for early detection of pancreatic cancer.

• EMT
• MKL-1
• STAT3
• The migration breast cancer cells
• miR-93-5p

• Biomarkers, Tumor/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/genetics
• Neoplasm Metastasis
• Ovarian Neoplasms/genetics
• Ovarian Neoplasms/pathology
• Translational Research, Biomedical

• Cluster Analysis
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Databases, Genetic
• Gene Regulatory Networks
• Humans
• Kaplan-Meier Estimate
• MicroRNAs/metabolism
• Prognosis
• RNA, Messenger/metabolism
• Support Vector Machine
• Transcriptome
• Up-Regulation

• PDK1
• miR-379
• microRNA
• osteosarcoma

• Adolescent
• Animals
• Base Sequence
• Cell Line, Tumor
• Cell Proliferation/genetics
• Child
• Disease Progression
• Down-Regulation/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice, Nude
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neoplasm Invasiveness
• Osteosarcoma/genetics
• Osteosarcoma/pathology
• Protein Serine-Threonine Kinases/genetics
• Protein Serine-Threonine Kinases/metabolism
• Pyruvate Dehydrogenase Acetyl-Transferring Kinase
• Up-Regulation/genetics
• Xenograft Model Antitumor Assays

Here we explore the role of microRNA-372 (miR-372) in tumorigenesis and development of endometrial adenocarcinoma (EC) and analyze the underlying mechanism. We found that miR-372 expression is much lower in EC than normal endometrial specimens. Cell function experiments demonstrated that miR-372 overexpression suppressed cell proliferation, migration, and invasion, and led to a G1 phase arrest and promoted the apoptosis of endometrial carcinoma cells in vitro. The nude mouse xenograft assay demonstrated that miR-372 overexpression suppressed tumor growth. RT-PCR and Western blot assays detected the expression of known targets of miR-372 in other malignant tumors and found Cyclin A1 and Cyclin-dependent Kinase 2 (CDK2) was downregulated by miR-372. Bioinformatic predictions and dual-luciferase reporter assays found that RhoC was a possible target of miR-372. RT-PCR and Western blot assays demonstrated that miR-372 transfection reduced the expression of RhoC, matrix metalloproteinase 2 (MMP2) and MMP9, while it increased the expression of cleaved poly (ADP ribose) polymerase (PARP) and bcl-2-associated X protein (Bax). The cell function experiments that transfected siRNA with RhoC showed the same trend as those which were transfected with miR-372. Taken together, our results demonstrated for the first time that miR-372 suppresses tumorigenesis and the development of EC; RhoC is a new and potentially important therapeutic target.

• RhoC
• endometrial carcinoma
• microRNA-372
• progression
• tumorigenesis

• 3' Untranslated Regions
• Antigens, CD/genetics
• Antigens, CD/metabolism
• Binding Sites
• Cadherins/genetics
• Cadherins/metabolism
• Cell Line, Tumor
• Cell Movement
• Cell Transformation, Neoplastic/genetics
• Cell Transformation, Neoplastic/metabolism
• Cell Transformation, Neoplastic/pathology
• Endometrial Neoplasms/genetics
• Endometrial Neoplasms/metabolism
• Endometrial Neoplasms/pathology
• Endometrium/metabolism
• Endometrium/pathology
• Epithelial-Mesenchymal Transition/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Genes, Reporter
• HEK293 Cells
• Hepatocyte Nuclear Factor 3-alpha/antagonists & inhibitors
• Hepatocyte Nuclear Factor 3-alpha/genetics
• Hepatocyte Nuclear Factor 3-alpha/metabolism
• Humans
• Luciferases/genetics
• Luciferases/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA, Small Interfering/genetics
• RNA, Small Interfering/metabolism
• Signal Transduction
• Transfection

• Natural Scientific Foundation of China

• Ovarian carcinoma
• biomarkers
• long non-coding RNA
• microRNA