MicroRNA-145 inhibits the malignant phenotypes of gastric carcinoma cells via downregulation of fascin 1 expression

Xue, Minghui; Zhao, Lunde; Yang, Fang; Li, Zhenjuan; Li, Guangyan

doi:10.3892/mmr.2015.4609

Cited by 14 publications

(17 citation statements)

References 35 publications

(43 reference statements)

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“…Previous studies showed that miR-138 is downregulated in OSCCs [ 19 , 20 ] and in silico target analysis revealed a conserved miR-138-binding site within 3' UTR of fascin mRNA ( www.targetscan.org ). Similarly, previous studies revealed that miR-145 regulates fascin expression in several different tumors [ 21 , 22 ]. miR-138 showed a significant and inverse correlation with fascin levels (rho=-0.68 and p=0.04), whereas no correlation was observed for miR-145 (Figure 11A ).…”

Section: Resultssupporting

confidence: 62%

Fascin promotes migration and invasion and is a prognostic marker for oral squamous cell carcinoma

et al. 2017

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Oral squamous cell carcinoma (OSCC) prognosis is related to clinical stage and histological grade. However, this stratification needs to be refined. We conducted a comparative proteome study in microdissected samples from normal oral mucosa and OSCC to identify biomarkers for malignancy. Fascin and plectin were identified as differently expressed and both are implicated in several malignancies, but the clinical impacts of aberrant fascin and plectin expression in OSCCs remains largely unknown. Immunohistochemistry and real-time quantitative PCR were carried out in ex vivo OSCC samples and cell lines. A loss-of-function strategy using shRNA targeting fascin was employed to investigate in vitro and in vivo the fascin role on oral tumorigenesis. Transfections of microRNA mimics were performed to determine whether the fascin overexpression is regulated by miR-138 and miR-145. We found that fascin and plectin are frequently upregulated in OSCC samples and cell lines, but only fascin overexpression is an independent unfavorable prognostic indicator of disease-specific survival. In combination with advanced T stage, high fascin level is also an independent factor of disease-free survival. Knockdown of fascin in OSCC cells promoted cell adhesion and inhibited migration, invasion and EMT, and forced expression of miR-138 in OSCC cells significantly decreased the expression of fascin. In addition, fascin downregulation leads to reduced filopodia formation and decrease on paxillin expression. The subcutaneous xenograft model showed that tumors formed in the presence of low levels of fascin were significantly smaller compared to those formed with high fascin levels. Collectively, our findings suggest that fascin expression correlates with disease progression and may serve as a prognostic marker and therapeutic target for patients with OSCC.

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Section: Resultssupporting

confidence: 62%

Fascin promotes migration and invasion and is a prognostic marker for oral squamous cell carcinoma

et al. 2017

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“…Several studies have shown that the interaction of miR-145 and miR-133 with FSCN1 is crucial to inhibit migration and invasion of cancer cells. 127–129 To our knowledge, it has not yet been associated with atherosclerosis and cardiovascular diseases. Reduction of miR-133a expression was associated with lower IGF1R levels and suppression of VSMC growth through modulation of the Akt/FOXO3a pathway.…”

Section: Resultsmentioning

confidence: 99%

Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review

et al. 2016

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The aim of the present study is to identify microRNAs (miRs) with high potential to be used as biomarkers in plasma and/or serum to clinically diagnose, or provide accurate prognosis for survival in, patients with atherosclerosis, coronary artery disease, and acute coronary syndrome (ACS). A systematic search of published original research yielded a total of 72 studies. After review of the risk of bias of the published studies, according to Cochrane Collaboration and the QUADUAS Group standards, 19 studies were selected. Overall 52 different miRs were reported. In particular, miR-133a/b (5 studies), miR-208a/b (6 studies), and miR-499 (7 studies) were well studied and found to be significant diagnostic and/or prognostic markers across different cardiovascular disease progression stages. miR-1 and miR-145b are potential biomarkers of ACS; miR-1 with higher sensitivity for all acute myocardial infarction (AMI), and miR-145 for STEMI and worse outcome of AMI. But when miRs were studied across different ACS study populations, patients had varying degrees of coronary stenosis, which was identified as an important confounder that limited the ability to quantitatively pool the study results. The identified miRs were found to regulate endothelial function and angiogenesis (miR-1, miR-133), vascular smooth muscle cell differentiation (miR-133, miR-145), communication between vascular smooth muscle and endothelial cell to stabilize plaques (miR-145), apoptosis (miR-1, miR-133, miR-499), cardiac myocyte differentiation (miR-1, miR-133, miR-145, miR-208, miR-499), and to repress cardiac hypertrophy (miR-133). Their role in these processes may be explained by regulation of shared RNA targets such as cyclin-dependent kinase inhibitor 1A (or p21), ETS proto-oncogene 1, fascin actin-bundling protein 1, hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, insulin-like growth factor 1 receptor LIM and SH3 protein 1, purine nucleoside phosphorylase, and transgelin 2. These mechanistic data further support the clinical relevance of the identified miRs. miR-1, miR-133a/b, miR-145, miR-208a/b, and miR-499(a) in plasma and/or serum show some potential for diagnosis of cardiovascular disease. However, biased selection of miRs in most studies and unexplained contrasting results are major limitations of current miR research. Inconsistencies need to be addressed in order to definitively identify clinically useful miRs. Therefore, this paper presents important aspects to improve future miR research, including unbiased selection of miRs, standardization/normalization of reference miRs, adjustment for patient comorbidities and medication, and robust protocols of data-sharing plans that could prevent selective publication and selective reporting of miR research outcomes.

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“…These results are consistent with previous research showing that miR‐181b was involved in transforming growth factor beta‐induced epithelial‐to‐mesenchymal transition and GC metastasis (Zhou et al ., ). Considering protective factors, we noted that miR‐145 could inhibit the malignant phenotypes and suppress metastasis of GC via different molecular mechanisms (Gao et al ., ; Lei et al ., ; Tong et al ., ; Xing et al ., ; Xue et al ., ; Zheng et al ., ). In another study, miR‐7‐3 was confirmed to be an independent prognostic indicator for stomach adenocarcinoma (Huo, ).…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide identification of a novel miRNA‐based signature to predict recurrence in patients with gastric cancer

Yang

Zhao

et al. 2018

Molecular Oncology

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The current tumor node metastasis (TNM) staging system is inadequate for identifying high‐risk gastric cancer (GC) patients. Using a systematic and comprehensive‐biomarker discovery and validation approach, we attempted to build a microRNA (miRNA)‐recurrence classifier (MRC) to improve the prognostic prediction of GC. We identified 312 differentially expressed miRNAs in 446 GC tissues compared to 45 normal controls by analyzing high‐throughput data from The Cancer Genome Atlas (TCGA). Using a Cox regression model, we developed an 11‐miRNA signature that could successfully discriminate high‐risk patients in the training set (n = 372; P < 0.0001). Quantitative real‐time polymerase chain reaction‐based validation in an independent clinical cohort (n = 88) of formalin‐fixed paraffin‐embedded clinical GC samples showed that MRC‐derived high‐risk patients succumb to significantly poor recurrence‐free survival in GC patients (P < 0.0001). Cox and stratification analysis indicated that the prognostic value of this signature was independent of clinicopathological risk factors. Time‐dependent receiver operating characteristic (ROC) analysis revealed that the area under the curve of this signature was significantly larger than that of TNM stage in the TCGA (0.733 vs. 0.589 at 3 years, P = 0.004; 0.802 vs. 0.635 at 5 years, P = 0.005) and validation cohort (0.835 vs. 0.689 at 3 years, P = 0.003). A nomogram was constructed for clinical use, which integrated both MRC and clinical‐related variables (depth of invasion, lymph node status and distance metastasis) and did well in the calibration plots. In conclusion, this novel miRNA‐based signature is superior to currently used clinicopathological features for identifying high‐risk GC patients. It can be readily translated into clinical practice with formalin‐fixed paraffin‐embedded specimens for specific decision‐making applications.

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MicroRNA-145 inhibits the malignant phenotypes of gastric carcinoma cells via downregulation of fascin 1 expression

Cited by 14 publications

References 35 publications

Fascin promotes migration and invasion and is a prognostic marker for oral squamous cell carcinoma

Fascin promotes migration and invasion and is a prognostic marker for oral squamous cell carcinoma

Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review

Genome‐wide identification of a novel miRNA‐based signature to predict recurrence in patients with gastric cancer

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