Evaluation of miRNA-expression and clinical tumour parameters in oral squamous cell carcinoma (OSCC)

Moratin, Julius; Hartmann, Stefan; Brands, Roman C.; Brisam, Muna; Mutzbauer, Grit; Scholz, Claus‐Jürgen; Seher, Axel; Müller‐Richter, Urs; Kübler, Alexander C.; Linz, Christian

doi:10.1016/j.jcms.2016.04.017

Cited by 19 publications

(9 citation statements)

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“…Thus, aberrant expression of hsa-miR-3156-5p may represent an important factor associated with obesity. Recent studies have predominantly focused on the association between hsa-miR-3156-5p and cancer ( 39 , 40 ), which has a similar inflammatory mechanism to obesity. However, the association between CD86 and obesity has been extensively studied.…”

Section: Discussionmentioning

confidence: 99%

Screening of exosomal miRNAs derived from subcutaneous and visceral adipose tissues: Determination of targets for the treatment of obesity and associated metabolic disorders

Yang

Wei

et al. 2018

Mol Med Report

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Exosomal micro (mi)RNAs have been suggested to have important roles in abdominal obesity, and to be associated with metabolic alterations via posttranscriptional regulation of target genes. However, exosomal miRNA profiles in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) have rarely been investigated. In the present study, microarray data were obtained from the Gene Expression Omnibus database with the following accession numbers: GSE68885 (exosomal miRNAs in SAT obtained from seven patients with obesity and five lean patients), GSE50574 (exosomal miRNAs in VAT obtained from seven patients with obesity and five lean patients) and GSE29718 [mRNAs in SAT (obtained from seven patients with obesity and eight lean patients) and VAT (obtained from three patients with obesity and two lean patients)]. Differentially expressed (DE)-miRNAs and differentially expressed genes (DEGs) were identified using the Linear Models for Microarray Data method, and mRNA targets of DE-miRNAs were predicted using the miRWalk2.0 database. Potential functions of DE-miRNA target genes were determined using the Database for Annotation, Visualization and Integrated Discovery. As a result, 10 exosomal DE-miRNAs were identified in SAT between patients with obesity and lean patients, while 58 DE-miRNAs were identified in VAT between patients with obesity and lean patients. miRNA (miR)-4517 was revealed to be a downregulated exosomal miRNA between SAT and VAT, while the other DE-miRNAs were SAT-(e.g. hsa-miR-3156-5p and hsa-miR-4460) or VAT-(e.g. hsa-miR-582-5p, hsa-miR-566 and miR-548) specific. Following overlapping with the target genes of DE-miRNAs, only one DEG [cluster of differentiation 86 (CD86)] was identified in SAT samples, whereas 25 DEGs (e.g. fibroblast growth factor 2 (FGF2), FOS like 2, AP-1 transcription factor subunit (FOSL2); and adenosine monophosphate deaminase 3 (AMPD3)] were identified in VAT samples. CD86 was revealed to be regulated by hsa-miR-3156-5p; whereas FGF2, FOSL2 and AMPD3 were revealed to be regulated by hsa-miR-582-5p, hsa-miR-566 and miR-548, respectively. Functional enrichment analysis demonstrated that these target genes may be associated with inflammation. In conclusion, exosomal miRNAs may represent underlying therapeutic targets for the treatment of abdominal obesity and metabolic disorders via regulation of inflammatory genes.

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Section: Discussionmentioning

confidence: 99%

Screening of exosomal miRNAs derived from subcutaneous and visceral adipose tissues: Determination of targets for the treatment of obesity and associated metabolic disorders

Yang

Wei

et al. 2018

Mol Med Report

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“…Additionally, fresh tissues were not analyzed. However, the number of patients appeared to be sufficient according to previous studies ( 83 – 85 , 134 , 135 ). Further studies that assess fresh cancer tissues and include a higher number of patients should be performed.…”

Section: Discussionmentioning

confidence: 85%

MicroRNA-196a-5p is a potential prognostic marker of delayed lymph node metastasis in early-stage tongue squamous cell carcinoma

et al. 2017

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MicroRNAs (miRs) are expected to serve as prognostic tools for cancer. However, many miRs have been reported as prognostic markers of recurrence or metastasis in oral squamous cell carcinoma patients. We aimed to determine the prognostic markers in early-stage tongue squamous cell carcinoma (TSCC). Based on previous studies, we hypothesized that miR-10a, 10b, 196a-5p, 196a-3p, and 196b were prognostic markers and we retrospectively performed miR expression analyses using formalin-fixed paraffin-embedded sections of surgical specimens. Total RNA was isolated from cancer tissues and adjacent normal tissue as control, and samples were collected by laser-capture microdissection. After cDNA synthesis, reverse transcription-quantitative polymerase chain reaction was performed. Statistical analyses for patient clinicopathological characteristics, recurrence/metastasis, and survival rates were performed to discern their relationships with miR expression levels, and the 2−ΔΔCq method was used. miR-196a-5p levels were significantly upregulated in early-stage TSCC, particularly in the lymph node metastasis (LNM) group. The LNM-free survival rate in the low miR-196a-5p ΔΔCq value regulation group was found to be lower than that in the high ΔΔCq value regulation group (P=0.0079). Receiver operating characteristic analysis of ΔΔCq values revealed that miR-196a-5p had a P-value=0.0025, area under the curve=0.740, and a cut-off value=−0.875 for distinguishing LNM. To our knowledge, this is the first study to examine LNM-related miRs in early-stage TSCC as well as miRs and ‘delayed LNM’ in head and neck cancer. miR-196a-5p upregulation may predict delayed LNM. Our data serve as a foundation for future studies to evaluate miR levels and facilitate the prediction of delayed LNM during early-stage TSCC, which prevent metastasis when combined with close follow-up and aggressive adjuvant therapy or elective neck dissection. Moreover, our data will serve as a foundation for future studies to evaluate whether miR-196a-5p can serve as a therapeutic marker for preventing metastasis.

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“…6 Clinical data show that miRNA dysregulation is related to tumor size, stage, lymph node metastasis, and other characteristics, which indicates the clinical value of miRNAs. 7 To date, numerous miRNAs have been monitored to be differentially expressed in OSCC by miRNA microarray analysis. 8 miR-186-5p is weakly expressed in whole blood samples from patients with OSCC compared to the healthy volunteers.…”

Section: Introductionmentioning

confidence: 99%

“…Micro RNAs (miRNAs) are key modulators in multiple biological processes, such as tumorigenesis, energy metabolism, inflammatory response, and autoimmunity 6 . Clinical data show that miRNA dysregulation is related to tumor size, stage, lymph node metastasis, and other characteristics, which indicates the clinical value of miRNAs 7 . To date, numerous miRNAs have been monitored to be differentially expressed in OSCC by miRNA microarray analysis 8 .…”

Section: Introductionmentioning

confidence: 99%

miR‐186‐5p inhibits the progression of oral squamous cell carcinoma by targeting ITGA6 to impair the activity of the PI3K/AKT pathway

Min

Zhang

2022

J Oral Pathology Medicine

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Background microRNAs (miRNAs) are pivotal regulators of multiple biological processes. miR‐186‐5p functions as a tumor suppressor in a variety of cancers and promotes the malignant proliferation of oral squamous cell carcinoma (OSCC). This study aimed to clarify the role and regulatory mechanism of miR‐186‐5p in OSCC. Methods The levels of miR‐186‐5p and integrin subunit alpha 6 (ITGA6) were investigated in clinical specimens and OSCC cell lines by reverse transcription‐quantitative polymerase chain reaction. The effects of miR‐186‐5p and ITGA6 on the cell migration, proliferation, and phosphatidylinositol 3‐kinase (PI3K)/serine‐threonine kinase (AKT) pathway activity were evaluated by transwell assay, cell counting kit 8 assay, and western blotting, respectively. A xenograft model was used to analyze the effect of miR‐186‐5p on tumor growth. Bioinformatic analyses were conducted to identify the putative targets of miR‐186‐5p in OSCC. Results Decreased miR‐186‐5p expression levels were observed in OSCC tumor tissues and cell lines. The overexpression of miR‐186‐5p suppressed the proliferation and migration of OSCC cells, and weakened the phosphorylation of PI3K and AKT. Moreover, the overexpression of miR‐186‐5p in xenograft tumor models impedes tumor growth. miR‐186‐5p is bound to ITGA6 and negatively related to ITGA6 expression in tumor tissues. The forced expression of ITGA6 promoted OSCC cell proliferation and migration and enhanced the phosphorylation levels of PI3K and AKT, while additional miR‐186‐5p enrichment partly abolished these effects. Conclusion miR‐186‐5p binds to ITGA6 to impair the activity of the PI3K/AKT signaling pathway, thereby blocking the development of OSCC. This study provides insight to understand the pathogenesis of OSCC.

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Evaluation of miRNA-expression and clinical tumour parameters in oral squamous cell carcinoma (OSCC)

Cited by 19 publications

References 50 publications

Screening of exosomal miRNAs derived from subcutaneous and visceral adipose tissues: Determination of targets for the treatment of obesity and associated metabolic disorders

Screening of exosomal miRNAs derived from subcutaneous and visceral adipose tissues: Determination of targets for the treatment of obesity and associated metabolic disorders

MicroRNA-196a-5p is a potential prognostic marker of delayed lymph node metastasis in early-stage tongue squamous cell carcinoma

miR‐186‐5p inhibits the progression of oral squamous cell carcinoma by targeting ITGA6 to impair the activity of the PI3K/AKT pathway

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