• Carcinoma-associated fibroblasts
• FAK pathway
• SCARA5
• extracellular vesicles
• miR-331-3p
• pancreatic cancer

• Animals
• Carcinoma/metabolism
• Cell Proliferation
• Extracellular Vesicles/metabolism
• Fibroblasts/metabolism
• Humans
• Mice
• Mice, Nude
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• Scavenger Receptors, Class A/metabolism
• Pancreatic Neoplasms

• Applied Basic Research Key Project of Yunnan

• Apoptosis
• Myristoylated Alanine Rich Protein Kinase C Substrate
• Renal cell carcinoma
• circ_0039569
• miR-133b

Esophageal cancer (EC) is a malignant tumor with high mortality. Correlations have been found between the expression level of tropomyosin 3 (TPM3) and the depth of tumor invasion, lymph node metastasis, and the 5-year survival rate. However, the specific mechanisms underlying EC remain unclear.

Stably transfected TPM3-overexpresing and TPM3-knockdown esophageal squamous cell carcinoma (ESCC) cell lines (ECa109 and EC9706) were constructed, and the association between TPM3 and the proliferation, invasion, and migration of ESCC was investigated using molecular biology methods. The associations between TPM3 and matrix metalloproteinase (MMP)2/9 or epithelial-mesenchymal transition (EMT)-related proteins were verified, and the potential tumor-promoting mechanism was explored by Gelatin Zymography Experiment.

TPM3 was found to promote the proliferation, migration, and metastatic potential of ESCC in vivo and in vitro, and stimulate the expression of MMP2/9 and certain EMT markers other than E-cadherin. The replenishment of MMP2/9 restored the malignant behavior of ESCC caused by TPM3. A gelatinase assay showed that the expression of TPM3 was related to the activity of MMP9.

TPM3 promoted proliferation, migration, and metastatic potential in EC cells. Additionally, TPM3 promoted the EMT process. This function may be achieved via the regulation the expression of MMP2/9.

• Tropomyosin 3 (TPM3)
• epithelial-mesenchymal transition (EMT)
• esophageal cancer (EC)
• matrix metalloproteinase 2 (MMP2)
• matrix metalloproteinase 9 (MMP9)

Neuroendocrine tumors (NETs) represent a tumor group that is both rare and heterogeneous. Prognosis is largely determined by the tumor grading and the site of the primary tumor and metastases. Despite intensive research efforts, only modest advances in diagnostic and therapeutic approaches have been achieved in recent years. For patients with non-respectable tumor stages, prognosis is poor. In this context, the development of novel diagnostic tools for early detection of NETs and prediction of tumor response to therapy as well as estimation of the overall prognosis would greatly improve the clinical management of NETs. However, identification of novel diagnostic molecules is hampered by an inadequate understanding of the pathophysiology of neuroendocrine malignancies. It has recently been demonstrated that microRNA (miRNA), a family of small RNA molecules with an established role in the pathophysiology of quite different cancer entities, may also play a role as a biomarker. Here, we summarize the available knowledge on the role of miRNAs in the development of NET and highlight their potential use as serum-based biomarkers in the context of this disease. We discuss important challenges currently preventing their use in clinical routine and give an outlook on future directions of miRNA research in NET.

• NET
• biomarker
• diagnosis
• miRNA
• prognosis

The present study aimed to evaluate the underlying mechanism of microRNA-203 (miR-203) in renal cell carcinoma (RCC) involving the PI3K/AKT signaling pathway. The results revealed downregulated miR-203 and upregulated CAV1 in RCC tissues. Upregulated miR-203 and downregulated CAV1 increased E-cadherin expression and cell apoptosis, decreased β-catenin and N-cadherin expression and cell proliferation, migration and invasion, and blocked cell cycle entry. CAV1, a target gene of miR-203, decreased by up-regulated miR-203, and silencing CAV1 led to the inactivation of PI3K/AKT signaling pathway. In conclusion, our findings suggested that miR-203-mediated direct suppression of CAV1 inhibits EMT of RCC cells via inactivation of the PI3K/AKT signaling pathway.

• CAV1
• MicroRNA-203
• PI3K/AKT signaling
• apoptosis
• epithelial-mesenchymal transformation
• invasion
• migration
• proliferation
• renal cell carcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because of diagnosis at late stage and inherent/acquired chemoresistance. Recent advances in genomic profiling and biology of this disease have not yet been translated to a relevant improvement in terms of disease management and patient’s survival. However, new possibilities for treatment may emerge from studies on key epigenetic factors. Deregulation of microRNA (miRNA) dependent gene expression and mRNA splicing are epigenetic processes that modulate the protein repertoire at the transcriptional level. These processes affect all aspects of PDAC pathogenesis and have great potential to unravel new therapeutic targets and/or biomarkers. Remarkably, several studies showed that they actually interact with each other in influencing PDAC progression. Some splicing factors directly interact with specific miRNAs and either facilitate or inhibit their expression, such as Rbfox2, which cleaves the well-known oncogenic miRNA miR-21. Conversely, miR-15a-5p and miR-25-3p significantly downregulate the splicing factor hnRNPA1 which acts also as a tumour suppressor gene and is involved in processing of miR-18a, which in turn, is a negative regulator of KRAS expression. Therefore, this review describes the interaction between splicing and miRNA, as well as bioinformatic tools to explore the effect of splicing modulation towards miRNA profiles, in order to exploit this interplay for the development of innovative treatments. Targeting aberrant splicing and deregulated miRNA, alone or in combination, may hopefully provide novel therapeutic approaches to fight the complex biology and the common treatment recalcitrance of PDAC.

• PDAC
• interaction
• miRNA
• splicing deregulation
• splicing modulation

• carcinoma
• larynx
• miRNA
• neuroendocrine
• poorly differentiated
• squamous

• metastasis
• miR-330
• migration
• renal cell carcinoma

• Apoptosis
• LASP1
• Lupus nephritis
• Proliferation
• miR-133

• DNMT1
• EZH2
• LINC00114
• colorectal cancer
• methylation
• miR-133b

Metastasis-associated protein 2 (MTA2) was previously known as a requirement to maintain malignant potentials in several human cancers. However, the role of MTA2 in the progression of renal cell carcinoma (RCC) has not yet been delineated. In this study, MTA2 expression was significantly increased in RCC tissues and cell lines. Increased MTA2 expression was significantly associated with tumour grade (p = 0.002) and was an independent prognostic factor for overall survival with a high RCC tumour grade. MTA2 knockdown inhibited the migration, invasion, and in vivo metastasis of RCC cells without effects on cell proliferation. Regarding molecular mechanisms, MTA2 knockdown reduced the activity, protein level, and mRNA expression of matrix metalloproteinase-9 (MMP-9) in RCC cells. Further analyses demonstrated that patients with lower miR-133b expression had poorer survival rates than those with higher expression from The Cancer Genome Atlas database. Moreover, miR-133b modulated the 3′untranslated region (UTR) of MMP-9 promoter activities and subsequently the migratory and invasive abilities of these dysregulated expressions of MTA2 in RCC cells. The inhibition of MTA2 could contribute to human RCC metastasis by regulating the expression of miR-133b targeting MMP-9 expression.

• MMP-9
• MTA2
• metastasis
• miR-133b
• renal cell carcinoma

• angiogenesis
• clear cell renal cell carcinoma
• epithelial-mesenchymal transition
• hypermethylated miRNA genes
• long non-coding RNA
• metastasis
• microRNA
• target genes

• Atherosclerosis
• MMP-9
• Vascular smooth muscle cells
• miR-133b

Osteosarcoma (OS) is the most common bone malignancy prevalent in children and young adults. MicroRNA-133b (miR-133b), through directly targeting the fibroblast growth factor receptor 1 (FGFR1), is increasingly recognized as a tumor suppressor in different types of cancers. However, little is known on the biological and functional significance of miR-133b/FGFR1 regulation in osteosarcoma.

The expressions of miR-133b and FGFR1 were examined by RT-qPCR and compared between 30 paired normal bone tissues and OS tissues, and also between normal osteoblasts and three OS cells lines, MG-63, U2OS, and SAOS-2. Using U2OS and MG-63 as the model system, the functional significance of miR-133b and FGFR1 was assessed on cell viability, proliferation, apoptosis, migration/invasion, and epithelial–mesenchymal transition (EMT) by overexpressing miR-133b and down-regulating FGFR1 expression, respectively. Furthermore, the signaling cascades controlled by miR-133b/FGFR1 were examined.

miR-133b was significantly down-regulated while FGFR1 robustly up-regulated in OS tissues and OS cell lines, when compared to normal bone tissues and normal osteoblasts, respectively. Low miR-133b expression and high FGFR1 expression were associated with location of the malignant lesion, advanced clinical stage, and distant metastasis. FGFR1 was a direct target of miR-133b. Overexpressing miRNA-133b or knocking down FGFR1 significantly reduced the viability, proliferation, migration/invasion, and EMT, but promoted apoptosis of both MG-63 and U2OS cells. Both the Ras/MAPK and PI3K/Akt intracellular signaling cascades were inhibited in response to overexpressing miRNA-133b or knocking down FGFR1 in OS cells.

miR-133b, by targeting FGFR1, presents a plethora of tumor suppressor activities in OS cells. Boosting miR-133b expression or reducing FGFR1 expression may benefit OS therapy.

• Fibroblast growth factor receptor 1
• Osteosarcoma
• PI3K/Akt signaling
• Ras/MAPK signaling
• Tumor suppressor
• miR-133b

• EMT
• microRNA
• signaling network

MicroRNAs (miRNAs) act a significant role in multiple biological processes and their associations with the development of all kinds of complex diseases are much close. In the research area of biology, medicine, and bioinformatics, prediction of potential miRNA-disease associations (MDAs) on the base of a variety of heterogeneous biological datasets in a short time is an important subject. Therefore, we proposed the model of Composite Network based inference for MiRNA-Disease Association prediction (CNMDA) through applying random walk to a multi-level composite network constructed by heterogeneous dataset of disease, long noncoding RNA (lncRNA) and miRNA. The results showed that CNMDA achieved an AUC of 0.8547 in leave-one-out cross validation and an AUC of 0.8533+/−0.0009 in 5-fold cross validation. In addition, we employed CNMDA to infer novel miRNAs for kidney neoplasms, breast neoplasms and lung neoplasms on the base of HMDD v2.0. Also, we employed the approach for lung neoplasms on the base of HMDD v1.0 and for breast neoplasms that have no known related miRNAs. It was found that CNMDA could be seen as an applicable tool for potential MDAs prediction.

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 well recognized that the presence of cervical lymph node metastasis is the most important prognostic factor in oral squamous cell carcinoma (OSCC). In solid epithelial cancer, the first step during the process of metastasis is the invasion of cancer cells into the underlying stroma, breaching the basement membrane (BM)—the natural barrier between epithelium and the underlying extracellular matrix (ECM). The ability to invade and metastasize is a key hallmark of cancer progression, and the most complicated and least understood. These topics continue to be very active fields of cancer research. A number of processes, factors, and signaling pathways are involved in regulating invasion and metastasis. However, appropriate clinical trials for anti-cancer drugs targeting the invasion of OSCC are incomplete. In this review, we summarize the recent progress on invasion-related factors and emerging molecular determinants which can be used as potential for diagnostic and therapeutic targets in OSCC.

• cell adhesion
• cell signaling
• epithelial mesenchymal transition (EMT)
• invasion
• metastasis
• microRNA
• oral squamous cell carcinoma
• tumor microenvironment

• Animals
• Biomarkers, Tumor
• Carcinoma, Squamous Cell/diagnosis
• Carcinoma, Squamous Cell/etiology
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/therapy
• Cell Adhesion
• Epithelial-Mesenchymal Transition
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/genetics
• Mouth Neoplasms/diagnosis
• Mouth Neoplasms/etiology
• Mouth Neoplasms/metabolism
• Mouth Neoplasms/therapy
• Neoplasm Invasiveness
• Signal Transduction
• Tumor Microenvironment

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

• Endometrial cancer
• Invasion
• MMP-9
• Migration
• Proliferation
• miR-183

• Cell Line, Tumor
• Cell Movement/physiology
• Cell Proliferation/physiology
• Endometrial Neoplasms/genetics
• Endometrial Neoplasms/metabolism
• Female
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• Matrix Metalloproteinase 9/genetics
• Matrix Metalloproteinase 9/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neoplasm Invasiveness/physiopathology
• Transcriptome

Although increasing evidence indicates that the deregulation of microRNAs (miRNAs) contributes to tumorigenesis and invasion, little is known about the role of miR-133b in human non-small cell lung cancer (NSCLC). In the present study, we revealed that the introduction of miR-133b dramatically suppressed NSCLC cell growth, migration, and invasion in vitro. On the contrary, miR-133b inhibitors promoted cell growth, migration, and invasion in vitro. Further studies revealed that matrix metallopeptidase 9 (MMP9) is a direct target gene of miR-133b. Silencing MMP9 inhibited cell growth, migration, and invasion of NSCLC cells, which was consistent with the effect of miR-133b overexpression. In clinical specimens, reduced miR-133b was an unfavorable factor and negatively correlated with MMP9 expression. Our studies demonstrate that miR-133b inhibits cell growth, migration, and invasion by targeting MMP9 in NSCLC.

• Bioinformatics
• Biomarkers
• Diabetic nephropathy
• Exosomes
• Urine
• miRNA

• glioma
• invasion
• microRNA-133b
• proliferation
• silent information regulator 1

• 3' Untranslated Regions/genetics
• Brain Neoplasms/genetics
• Brain Neoplasms/metabolism
• Brain Neoplasms/pathology
• Cell Line, Tumor
• Cell Proliferation/genetics
• Gene Expression Regulation, Neoplastic
• Glioma/genetics
• Glioma/metabolism
• Glioma/pathology
• Humans
• MicroRNAs/genetics
• Neoplasm Invasiveness
• Reverse Transcriptase Polymerase Chain Reaction
• Sirtuin 1/genetics
• Sirtuin 1/metabolism

• miR-133b
• prognosis
• progression
• urothelial carcinoma of the bladder

• EGFR
• RCC
• microRNA
• proliferation

• mmps
• timps
• mirna
• epigenetics
• extracellular matrix
• atherosclerosis
• cardiovascular
• review

• Humans
• Matrix Metalloproteinases/metabolism
• Vascular Diseases/enzymology

• R01 HL104103 NHLBI NIH HHS
• R01 HL108621 NHLBI NIH HHS
• R01 NS084823 NINDS NIH HHS
• HL-108621 NHLBI NIH HHS

Increasing evidence has suggested that microRNA-133b (miR-133b) is important in regulating the genesis of different types of cancer. However, the effects and the underlying mechanisms of miR-133b in the development of glioblastoma (GBM) remain largely unknown. The aim of the present study was to investigate the role of miR-133b in GBM and to determine the molecular mechanisms underlying its action. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression levels of miR-133b in 21 human GBM samples and 9 normal brain tissue samples. A wound healing assay, and Transwell migration and invasion assays were used to evaluate the effects of miR-133b on cell migration and invasion. Western blotting and a luciferase reporter assay were used to identify the target genes of miR-133b. It was found that miR-133b suppressed GBM cell migration and invasion, and matrix metalloproteinase 14 (MMP14) was identified as a direct target gene. In conclusion, miR-133b may suppress GBM migration and invasion through directly targeting MMP14, highlighting its potential as a novel agent for the treatment of GBM invasion.

• glioblastoma
• invasion
• matrix metalloproteinase 14
• microRNA-133b
• migration

MicroRNAs are small non-coding RNAs that participate in different biological processes, providing subtle combinational regulation of cellular pathways, often by regulating components of signalling pathways. Aberrant expression of miRNAs is an important factor in the development and progression of disease. The canonical myomiRs (miR-1, -133 and -206) are central to the development and health of mammalian skeletal and cardiac muscles, but new findings show they have regulatory roles in the development of other mammalian non-muscle tissues, including nerve, brain structures, adipose and some specialised immunological cells. Moreover, the deregulation of myomiR expression is associated with a variety of different cancers, where typically they have tumor suppressor functions, although examples of an oncogenic role illustrate their diverse function in different cell environments. This review examines the involvement of the related myomiRs at the crossroads between cell development/tissue regeneration/tissue inflammation responses, and cancer development.

• Muscle microRNAs
• MiR-1
• MiR-206
• MiR-133a
• MiR-133b
• Cell development
• Cancer

• R01 AA022701 NIAAA NIH HHS

• GSTP1
• epigenetics
• miRNA
• oxidative DNA damage
• prostate cancer

Despite recent advances in the understanding of the biology of renal cell carcinoma (RCC), successful surgical treatment and implementation of novel-targeted therapies, the prognosis for RCC patients remains poor. Late presentation, tumor heterogeneity and in particular the lack of molecular biomarkers for early detection, classification and the surveillance of RCC treatments are major obstacles. The increasing knowledge regarding the functional role of microRNAs (miRNAs) in pathophysiological processes may provide an important link to the identification of suitable therapeutic targets and diagnostic/prognostic biomarkers for RCC. The aim of this review was to provide new insight into the function of miRNAs in the pathogenesis of RCC and to emphasize their potential as diagnostic and prognostic markers, as well as therapeutic targets.