• CXCR2P1
• PD-1 inhibitor
• immune microenvironment
• microRNAs
• prognosis

• Humans
• Stomach Neoplasms/immunology
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/mortality
• Stomach Neoplasms/pathology
• Tumor Microenvironment/immunology
• Immune Checkpoint Inhibitors/therapeutic use
• Immune Checkpoint Inhibitors/pharmacology
• Gene Expression Regulation, Neoplastic
• Lymphocytes, Tumor-Infiltrating/immunology
• Lymphocytes, Tumor-Infiltrating/metabolism
• Programmed Cell Death 1 Receptor/antagonists & inhibitors
• Prognosis
• Databases, Genetic
• Biomarkers, Tumor/genetics
• Gene Expression Profiling
• Signal Transduction

• Beijing Science and Technology Planning Project

• ABO blood group
• Blood group antigen expression
• Erythropoiesis
• MiRNA

• EVs
• early diagnosis
• exosomes
• gastric cancer
• gastric juice
• liquid biopsy
• miRNA

• Humans
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Extracellular Vesicles/metabolism
• Extracellular Vesicles/genetics
• MicroRNAs/metabolism
• MicroRNAs/genetics
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Liquid Biopsy/methods

• early diagnosis
• extracellular vesicle
• gastric cancer
• long non-coding RNA
• microRNA

• Cancer therapeutics
• Runt-related transcription factor
• Signal transduction
• Tumorigenesis

• Humans
• Transcription Factors/metabolism
• Core Binding Factor alpha Subunits/metabolism
• Neoplasms/genetics
• Carcinogenesis/genetics

• BT/HRD/35/02/2006 Department of Biotechnology, Ministry of Science and Technology, India

• circulatory miRNAs
• diagnostics
• miR-125b
• miR-142-3p
• miR-148a
• miR-215
• miR-223
• psoriasis

• haematopoietic stem cells
• stem-cell research

• Humans
• Erythropoiesis/genetics
• ABO Blood-Group System/genetics
• Hematocrit
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Hematopoietic Stem Cells/metabolism
• Cell Differentiation/genetics

• Barrett’s esophagus
• adenocarcinoma
• epigenetics
• methylations
• miRNA

• Prostate cancer
• ROC
• differentially expressed miRNA
• microRNA
• plasma

The active metabolite of 5-Fluorouracil (5FU), used in the treatment of several types of cancer, acts by inhibiting the thymidylate synthase encoded by the TYMS gene, which catalyzes the rate-limiting step in DNA replication. The major failure of 5FU-based cancer therapy is the development of drug resistance. High levels of TYMS-encoded protein in cancerous tissues are predictive of poor response to 5FU treatment. Expression of TYMS is regulated by various mechanisms, including involving non-coding RNAs, both miRNAs and long non-coding RNAs (lncRNAs).

To delineate the miRNAs and lncRNAs network regulating the level of TYMS-encoded protein.

Several miRNAs targeting TYMS mRNA have been identified in colon cancers, the levels of which can be regulated to varying degrees by lncRNAs. Due to their regulation by the MALAT1 lncRNA, these miRNAs can be divided into three groups: (1) miR-197-3p, miR-203a-3p, miR-375-3p which are downregulated by MALAT1 as confirmed experimentally and the levels of these miRNAs are actually reduced in colon and gastric cancers; (2) miR-140-3p, miR-330-3p that could potentially interact with MALAT1, but not yet supported by experimental results; (3) miR-192-5p, miR-215-5p whose seed sequences do not recognize complementary response elements within MALAT1. Considering the putative MALAT1-miRNAs interaction network, attention is drawn to the potential positive feedback loop causing increased expression of MALAT1 in colon cancer and hepatocellular carcinoma, where YAP1 acts as a transcriptional co-factor which, by binding to the TCF4 transcription factor/ β-catenin complex, may increase the activation of the MALAT1 gene whereas the MALAT1 lncRNA can inhibit miR-375-3p which in turn targets YAP1 mRNA.

The network of non-coding RNAs may reduce the sensitivity of cancer cells to 5FU treatment by upregulating the level of thymidylate synthase.

• 5-FU resistance
• Capecitabine
• Chemoresistance
• Colorectal cancer
• Hippo-YAP
• Micro RNA
• Wnt beta-catenin
• ceRNA network
• miRNAs

Introduction: Exosomal microRNAs (miRNAs) are emerging diagnostic biomarkers for different types of cancers. We aim to detect gastric cancer (GC)-specific miRNAs in serum exosomes with diagnostic potential.

Methods: A pair of 43 tumor and tumor-adjacent tissue biopsies obtained from GC patients, also 5 mL peripheral blood (following 12h fasting) were collected from the same patients and healthy controls (HCs). QIAGEN miRCURY LNA miRNA Focus PCR Panel applied to screen differentially expressed onco-miRNAs. The candidate miRNAs with the highest fold changes proceeded for validation by qRT-PCR in individuals.

Results: We identified that exosomal miR-10a-5p, miR-19b-3p, miR-215-5p, and miR-18a-5p were significantly upregulated in GC patient’s exosomes in contrast to HCs exosomes, Roc curve analysis indicated area under the ROC curve (AUC) of 0.801, 0.721, 0.780 and 0.736 respectively. The Roc curve analysis for the combined signature of four exosomal miRNAs indicated AUC of 0.813. Also, Spearman's correlation coefficients indicated that the miRNA expression is highly correlated between tumor and exosome.

Conclusion: Herein, we specifically identified four miRNAs in serum exosomes of GC patients for a diagnostic purpose which are directly associated with tumoral miRNA expression profile.

• ExomiR
• Liquid Biopsy
• OncomiR
• Stem Loop RT-PCR
• Stomach

• Atrophic gastritis
• Biomarkers
• Gastric cancer
• Helicobacter pylori
• MicroRNAs
• Tumorigenesis

• Biomarkers
• Gastritis, Atrophic/diagnosis
• Gastritis, Atrophic/genetics
• Humans
• MicroRNAs/genetics
• Real-Time Polymerase Chain Reaction
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics

• RUNX1
• circ_0027599
• gastric cancer
• miR-21-5p

• CFTR
• Invasion
• Lung adenocarcinoma
• Methylation
• Migration
• Proliferation

• NF-κB signaling pathway
• gastric cancer
• long non-coding RNAs
• microRNAs

MiRNAs have been proven to modulate the progression of gastric cancer (GC). In this field, we evaluated the role and mechanism of miR-140-3p in GC.

Western blotting and qRT-PCR were used to detect the levels of miR-140-3p and BCL2. The interaction of miR-140-3p and BCL2 was confirmed by dual-luciferase reporter and miRNA pull-down assays. CCK-8, EdU, wound healing, and Transwell invasion assays were performed to evaluate cell proliferation, migration and invasion. Autophagy was analyzed using Western blot analysis of the LC3-II/I ratio and immunofluorescence staining. A xenograft model was established to reveal the role of miR-140-3p in tumorigenesis.

In GC cell lines and tissues, miR-140-3p was highly expressed, and BCL2 was expressed at low levels. MiR-140-3p directly inhibited BCL2 expression and indirectly promoted BECN1 expression, and BCL2 inhibited BECN1 expression. MiR-140-3p overexpression or silencing restrained or facilitated migration, invasion and EMT in GC cells. Moreover, we noticed that overexpression or downregulation of miR-140-3p promoted or suppressed BECN1-dependent autophagy in GC cells. BCL2 introduction or BECN1 silencing in GC cells partially blocked the effects of miR-140-3p. In conclusion, miR-140-3p directly downregulated the expression of BCL2, BCL2 downregulation further activated BECN1-dependent autophagy, and autophagy activation further inhibited EMT.

miR-140-3p may act as a tumor suppressor by targeting BCL2 and regulating downstream BECN1-induced autophagy and metastasis in GC progression.

• BCL2
• BECN1
• EMT
• autophagy
• gastric cancer
• miR-140-3p

• Apoptosis
• clinical prognosis
• gastric cancer xenograft models
• invasion
• microRNA targets and inhibitors
• migration
• proliferation
• review.
• tumor growth and metastasis

• gastric cancer
• serum extracellular vesicle mir-215-5p
• early tumor recurrence
• prognosis
• diagnosis

• Biomarkers, Tumor
• Extracellular Vesicles
• Humans
• MicroRNAs
• Neoplasm Recurrence, Local
• Prognosis
• Stomach Neoplasms/genetics

Decreased expression of miR-215-5-p was found in tumor tissue of patients with colorectal cancer (CRC) in comparison to healthy colon tissue. Moreover, expression levels of miR-215-5p were further decreased in metastatic lesions compared to primary tumor tissue. Overall, CRC patients with lower expression of miR-215-5p in tumors had significantly shorter overall survival and a higher chance of metastasis. This study aimed to examine the effects of miR-215-5p supplementation on the metastatic potential of CRC. MiR-215-5p was found to decrease invasiveness, migratory capacity, tumorigenicity, and metastasis formation. Finally, transcriptome analysis identified signaling pathways involved in the process, and subsequent RT-qPCR validation indicates CTNNBIP1 to be a direct target of this microRNA. These results bring new insight into miR-215-5p biology, a molecule that could potentially serve as a promising target for CRC patients’ future therapeutic strategies.

Background: Growing evidence suggests that miR-215-5p is a tumor suppressor in colorectal cancer (CRC); however, its role in metastasis remains unclear. This study evaluates the effects of miR-215 overexpression on the metastatic potential of CRC. Methods: CRC cell lines were stably transfected with miR-215-5p and used for in vitro and in vivo functional analyses. Next-generation sequencing and RT-qPCR were performed to study changes on the mRNA level. Results: Overexpression of miR-215-5p significantly reduced the clonogenic potential, migration, and invasiveness of CRC cells in vitro and tumor weight and volume, and liver metastasis in vivo. Transcriptome analysis revealed mRNAs regulated by miR-215-5p and RT-qPCR confirmed results for seven selected genes. Significantly elevated levels of CTNNBIP1 were also observed in patients’ primary tumors and liver metastases compared to adjacent tissues, indicating its direct regulation by miR-215-5p. Gene Ontology and KEGG pathway analysis identified cellular processes and pathways associated with miR-215-5p deregulation. Conclusions: MiR-215-5p suppresses the metastatic potential of CRC cells through the regulation of divergent molecular pathways, including extracellular-matrix-receptor interaction and focal adhesion. Although the specific targets of miR-215-5p contributing to the formation of distant metastases must be further elucidated, this miRNA could serve as a promising target for CRC patients’ future therapeutic strategies.

• colorectal cancer
• extracellular matrix-receptor interaction
• focal adhesion
• metastasis
• miR-215-5p

• MYL9
• Osteosarcoma
• lncRNA GAS5
• miR-663a

• Cell Movement/genetics
• Cell Proliferation/genetics
• Colorectal Neoplasms/enzymology
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Computational Biology
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• HT29 Cells
• Humans
• MicroRNAs/genetics
• Mutation
• Neoplasm Invasiveness/genetics
• Neoplasm Invasiveness/pathology
• Neoplasm Invasiveness/prevention & control
• Stearoyl-CoA Desaturase/antagonists & inhibitors
• Stearoyl-CoA Desaturase/genetics
• Up-Regulation

IARS2, which encodes the mitochondrial form of isoleucyl-tRNA synthetase, has been found to play an important role in a range of diseases, including cancer. However, the relationship between IARS2 and melanoma is still unclear. To evaluate the role of IARS2 in melanoma, we constructed a stable A375 cell line with IARS2 knockdown via lentivirus-mediated small interfering RNAs. The expression of IARS2 was measured by real time-quantitative Polymerase Chain Reaction and western blot analysis. Cell counting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and colony formation assay were conducted to assess the effect of IARS2 on melanoma cell proliferation. Flow cytometry assay was used to determine cell apoptosis and cell cycle distribution in melanoma A375 cells. Finally, immunohistochemistry was employed to validate the expression of IARS2 protein in melanoma tissues. In this study it was found that IARS2 was highly expressed in melanoma cell lines. Furthermore, IARS2 protein also exhibited elevated expression in the tumour tissues obtained from melanoma patients. After suppression of the mRNA expression of IARS2, the proliferation and colony formation ability of the A375 cells were significantly inhibited, while the proportion of apoptotic A375 cells increased significantly, as indicated by an enhanced phosphatidylserine externalization and caspase 3/7 activity after IARS2 knockdown. Further investigations found that knockdown of IARS2 arrested cells in the G1 phase. The results suggested that IARS2 is critical for proliferation and apoptosis of melanoma cells.

• IARS2
• RNAi-mediated knockdown
• apoptosis
• growth
• melanoma

Runt-related transcription factor 1 (RUNX1) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters and can accelerate apoptosis in various tumors. However, the regulatory mechanisms underlying RUNX1 expression in neuroblastoma (NB), a highly malignant tumor in childhood, remain largely unclear. In this study, we aimed to assess the role of RUNX1 in NB and to reveal the underlying mechanisms that may contribute to finding a potential therapeutics strategy against NB.

Growth, invasion, metastasis and angiogenesis were assessed using Cell Counting Kit-8 (CCK-8) immunocytochemistry, and studies involving soft agar, cell invasion, tube formation and whole animals. The levels of expression were measured using real-time quantitative PCR for RNA, Western blot and immunostaining analyses for proteins. Luciferase reporter and chromatin immunoprecipitation assays indicated that RUNX1 directly binds within the BIRC5, CSF2RB and NFKBIA promoter regions to facilitate transcription. The level of apoptosis was assessed by determining mitochondrial membrane potential and flow cytometry.

RUNX1 was highly expressed in ganglioneuroma (GN) and well-differentiated (WD) tissues relative to the poorly differentiated (PD) and undifferentiated (UD) ones. Moreover, RUNX1 effectively reduced cell viability, invasion, metastasis, angiogenesis, and promoted apoptosis in vitro and in vivo. RUNX1 reduced BIRC5 transcription and increased CSF2RB and NFKBIA transcription by directly binding BIRC5, CSF2RB and NFKBIA promoters. In addition, cytotoxic drugs, especially cisplatin, significantly increased RUNX1 expression in NB cells and promoted apoptosis.

These data show that RUNX1 is an independent surrogate marker for the progression of NB and it can be used for monitoring NB prognosis during therapy.

• Neuroblastoma-prognosis
• Transcription factor
• Transcription regulation
• Tumor progression

• gastric cancer
• miR-515-3p
• serum biomarker

Background: The biological role of microRNAs (miRNAs) in field cancerization is unknown. To investigate the involvement of miRNAs in gastric field cancerization, we evaluated the expression profile of ten miRNAs and their diagnostic value.

Methods: We used three groups of FFPE gastric samples: non-cancer (NC), cancer adjacent (ADJ) and gastric cancer (GC). The expression profiles of hsa-miR-10a, -miR-21, -miR-29c, -miR-135b, -miR-148a, -miR-150, -miR-204, -miR-215, -miR-483 and -miR-664a were investigated using qRT-PCR. The results obtained by qRT-PCR were validated in Small RNA-Seq data from the TCGA database. The search for target genes of the studied miRNAs was performed in the miRTarBase public database and miRTargetLink tool, using experimentally validated interactions. In addition, we also performed the functional analysis of these genes using enrichment in KEGG pathways. The potential as biomarker was evaluated using a receiver operating characteristic (ROC) curve and the derived area under the curve (AUC>0.85) analysis.

Results: The miRNAs hsa-miR-10a, -miR-21, -miR-135b, hsa-miR-148a, -miR-150, -miR-215, -miR-204, -miR-483 and -miR-664a were up-regulated in ADJ and GC compared to NC (P<0.03); and hsa-miR-21 and -miR-135b were up-regulated in GC compared to ADJ (P<0.01). Hsa-miR-148a, -miR-150, -miR-215, -miR-483 and -miR-664a were not differentially expressed between GC and ADJ, suggesting that both share similar changes (P>0.1). The TS-miR hsa-miR-29c was up-regulated in ADJ compared to NC and GC (P<0.01); we did not observe a significant difference in the expression of this miRNA between NC and GC. This feature may be an antitumor mechanism used by cancer-adjacent tissue because this miRNA regulates the BCL-2, CDC42 and DMNT3A oncogenes. The expression level of hsa-miR-204 was associated with Helicobacter pylori infection status (P<0.05). Functional analysis using the genes regulated by the studied miRNAs showed that they are involved in biological pathways and cellular processes that are critical for the establishment of H. pylori infection and for the onset, development and progression of GC. hsa-miR-10a, -miR-21, -miR-135b, -miR-148a, -miR-150, -miR-215, -miR-483 and -miR-664a were able to discriminate NC from other tissues with great accuracy (AUC>0.85).

Conclusion: The studied miRNAs are closely related to field cancerization, regulate genes important for gastric carcinogenesis and can be potentially useful as biomarkers in GC.

• biomarker
• epigenetic
• field cancerization
• gastric cancer
• miRNA

• Gastric cancer
• Poor-survival
• RUNX1
• SRPX2
• Sialyl-Tn

• Gastric cancer
• H19
• MEG3
• miR-141-3p
• miR-148a-3p
• miR-181a-5p
• miR-675-5p

• Gastric cancer
• RUNX1
• Y-box binding protein-1 (YBX1)
• circFAT1(e2)
• miR-548g

• Biomarker
• DNA methylation
• gastric cancer
• long noncoding RNA
• microRNA

Gastric cancer (GC) is a prevalent malignant cancer of digestive system. To identify key genes in GC, mRNA microarray GSE27342, GSE29272, and GSE33335 were downloaded from GEO database.

Differentially expressed genes (DEGs) were obtained using GEO2R. DAVID database was used to analyze function and pathways enrichment of DEGs. Protein-protein interaction (PPI) network was established by STRING and visualized by Cytoscape software. Then, the influence of hub genes on overall survival (OS) was performed by the Kaplan-Meier plotter online tool. Module analysis of the PPI network was performed using MCODE. Additionally, potential stem loop miRNAs of hub genes were predicted by miRecords and screened by TCGA dataset. Transcription factors (TFs) of hub genes were detected by NetworkAnalyst.

In total, 67 DEGs were identified; upregulated DEGs were mainly enriched in biological process (BP) related to angiogenesis and extracellular matrix organization and the downregulated DEGs were mainly enriched in BP related to ion transport and response to bacterium. KEGG pathways analysis showed that the upregulated DEGs were enriched in ECM-receptor interaction and the downregulated DEGs were enriched in gastric acid secretion. A PPI network of DEGs was constructed, consisting of 43 nodes and 87 edges. Twelve genes were considered as hub genes owing to high degrees in the network. Hsa-miR-29c, hsa-miR-30c, hsa-miR-335, hsa-miR-33b, and hsa-miR-101 might play a crucial role in hub genes regulation. In addition, the transcription factors-hub genes pairs were displayed with 182 edges and 102 nodes. The high expression of 7 out of 12 hub genes was associated with worse OS, including COL4A1, VCAN, THBS2, TIMP1, COL1A2, SERPINH1, and COL6A3.

The miRNA and TFs regulation network of hub genes in GC may promote understanding of the molecular mechanisms underlying the development of gastric cancer and provide potential targets for GC diagnosis and treatment.

The online version of this article (10.1186/s12957-018-1409-3) contains supplementary material, which is available to authorized users.

• Bioinformatics analysis
• Differentially expressed genes
• Gastric cancer
• Prognosis

Endometrial cancer (EC) is the most common gynecological tumor in developed countries with an increasing incidence. Left-right determination factor 2 (LEFTY2), a suppressor of cell proliferation and tumor growth, is a negative regulator of EC progression. The roles of LEFTY2 are emerging; however, the regulatory mechanisms of its expression have not been well understood. MicroRNA (miR)-215 as an oncogene serves an important role in tumorigenesis by regulating target genes. In the present study, it was demonstrated that overexpression of miR-215 promoted epithelial to mesenchymal transition (EMT), colony formation and DNA synthesis in EC HEC-1A cells and its expression was upregulated in EC tissues. Using online miR target prediction software, it was revealed that LEFTY2 is predicted as a target of miR-215. Using western blot analysis and immunofluorescence assays, it was demonstrated that overexpression of miR-215 markedly downregulated LEFTY2 protein expression levels in HEC-1A cells and LEFTY2 protein expression was downregulated in EC tissues, which was inversely correlated with miR-215 expression. Furthermore, the present study indicated that overexpression of LEFTY2 protein promoted mesenchymal to epithelial transition and sensitized HEC-1A cells to cisplatin treatment. In addition, it was revealed that the overexpression of LEFTY2 inhibited colony formation and DNA synthesis in HEC-1A cells. Thus, miR-215 may promote EMT and proliferation by regulating LEFTY2 in EC.

The clinical prognosis of malignant gliomas is poor and PCDH9 down-regulation is strongly associated with its poor prognosis. But the mechanism of PCDH9 down-regulation is unknown. Abnormal miRNAs profiles regulate tumor phenotypes through inhibiting their target genes and miRNAs could inhibit target genes more efficiently by binding to both the promoter and 3′UTR of target genes. In this study, to search the dual inhibitory miRNAs which suppress PCDH9 expression in gliomas, we performed an integrative analysis of databases including miRDB, TargetScan, microPIR and miRCancer. We identified three candidate miRNAs which were predicted to bind both the promoter and 3′UTR of PCDH9 and up-regulated in gliomas. Then, we validated miR-215-5p up-regulation and PCDH9 down-regulation in glioma samples and demonstrated that miR-215-5p could inhibit the mRNA and protein levels of PCDH9 in glioma cell lines by targeting its promoter and 3′ UTR at the same time. Moreover, miR-215-5p could increase glioma cell proliferation, clone formation, in-vitro migration and reduce apoptosis via inhibiting PCDH9 expression. Our study provides evidence for a novel dual inhibition of PCDH9 by miR-215-5p in gliomas and suggests that miR-215-5p might be a therapeutic target for the treatment of gliomas.

• PCDH9
• glioma
• integrative analysis
• miR-215-5p
• miRNA

• PI3K-Akt
• SRPX2
• colon cancer
• miR-192
• miR-215

The present study investigated the expression of microRNA (miR)-215 in non-small cell lung carcinoma (NSCLC) at tissue and cellular levels, as well as its biological functions and mechanism of action. A total of 56 patients with NSCLC were included in the present study. NSCLC tissues and tumor-adjacent normal tissues were resected and collected. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression of miR-215. Following transfection with miR-215 mimics, A549 cell proliferation, migration and invasion were determined using a Cell Counting Kit-8 and Transwell assay. Western blotting was employed to measure the expression of matrix metalloproteinase (MMP)-16 protein. A dual-luciferase reporter assay was conducted to determine the existence of a direct interaction between miR-215 and the MMP-16 gene. Reduced expression of miR-215 in NSCLC was closely associated with lymphatic metastasis and TNM staging. Overexpression of miR-215 inhibited the proliferation of A549 cells in vitro. Upregulated expression of miR-215 inhibited the migration and invasion of A549 cells in vitro. miR-215 exerted its biological functions possibly by regulating the expression of MMP-16. Elevated expression of MMP-16 promoted the proliferation, migration and invasion of A549 cells. miR-215 regulated the proliferation, migration and invasion of A549 cells by binding with the seed 3′-untranslated region of MMP-16 mRNA. The present study demonstrates that reduced expression of miR-215 in NSCLC is negatively associated with lymphatic metastasis and TNM staging. In addition, miR-215 acts as a tumor suppressor gene by inhibiting the proliferation, migration and invasion of NSCLC cells via the downregulation of MMP-16 expression.

• matrix metalloproteinase-16
• microRNA-215
• non-small cell lung carcinoma

This study aimed to investigate the effect and underlying mechanism of lncRNA CASC2 in malignant melanoma (MM). Expression of CASC2 in MM tissues and cells was detected. A375 cells were transfected with pc-CASC2, si-CASC2, miR-18a-5p inhibitor, or corresponding controls, and then cell proliferation, migration, and invasion were detected using MTT assay, colony formation assay, and Transwell analysis, respectively. The relationship of miR-18a-5p and CASC2 or RUNX1 was detected by luciferase reporter assay. The levels of CASC2 and RUNX1 were significantly reduced in MM tissues compared with normal skin tissues or cells, while the miR-18a-5p level was obviously increased (all p < 0.01). Cell viability, colony number, migration, and invasion were significantly decreased in cells with pc-CASC2 compared with cells transfected with pcDNA3.1 (all p < 0.05). These effects were consistent with the cells transfected with miR-18a-5p inhibitor. The luciferase reporter assay revealed that CASC2 acted as a molecular sponge for miR-18a-5p, and RUNX1 was a target gene of miR-18a-5p. Moreover, CASC2 overexpression promoted the expression of RUNX1, while upregulated miR-18a-5p significantly reversed the effect of CASC2 on the RUNX1 level (all p < 0.05). Upregulated CASC2 may inhibit cell proliferation, migration, and invasion through regulating miR-18a-5p and its target gene RUNX1 in MM.

• HMGA2 (High mobility group AT-hook 2)
• RUNX1
• miR-93
• pancreatic ductal adenocarcinoma (PDAC)
• tumor progression

This work aims to elucidate the effects and the potential underlying mechanisms of microRNA-216a-3p (miR-216a-3p) on the proliferation, migration, and invasion of gastric cancer (GC) cells. In this study, we revealed that the expression of miR-216a-3p was significantly elevated in GC tissues and cell lines. The different expression level of miR-216a-3p was firmly correlated with clinicopathological characteristics of GC patients. We next demonstrated that upregulation of miR-216a-3p could dramatically promote the ability of proliferation, migration, and invasion of GC cells using a series of experiments, whereas downregulation essentially inhibited these properties. Additionally, through bioinformatics analysis and biological approaches, we confirmed that runt-related transcription factor 1 (RUNX1) was a direct target of miR-216a-3p, and overexpression of RUNX1 could reverse the potential effect of miR-216a-3p on GC cells. Furthermore, mechanistic investigation using Western blot analysis showed that downregulation of RUNX1 by miR-216a-3p could stimulate the activation of NF-κB signaling pathway. In summary, this work proved that miR-216a-3p can promote GC cell proliferation, migration, and invasion via targeting RUNX1 and activating the NF-κB signaling pathway. Therefore, miR-216a-3p/RUNX1 could be a possible molecular target for innovative therapeutic agents against GC.

• MicroRNA
• biomarker
• glioma
• serum

• Cancer
• Circulating tumor cells
• Disseminating tumor cells
• Metastasis
• Metastatic cascade
• MicroRNA signatures
• MicroRNAs
• Therapeutic targets

• Gastric cancer
• Invasion
• Migration
• RB1
• miR-215

• AKT serine/threonine kinase
• breast cancer
• microRNA-215
• targeted therapy
• tumor suppressor

• MicroRNAs
• NOB1
• epithelial ovarian cancer
• miR-215

• Anti-OncomiR
• EMT
• Metastasis
• MiRNA-mimics
• miRNA

• Gene Expression Regulation, Neoplastic
• Genomics
• Humans
• MicroRNAs/genetics
• Neoplasm Metastasis/genetics
• Neoplasm Metastasis/therapy
• Neoplasms/genetics
• Neoplasms/pathology
• Neoplasms/therapy

• C06 RR030414 NCRR NIH HHS
• P50 CA070907 NCI NIH HHS

• lung cancer
• miR-215
• microRNA
• migration
• non-small cell lung cancer