• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10355-10361
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• 2015

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules found in multicellular eukaryotes which are implicated in development of cancer, including cutaneous squamous cell carcinoma (cSCC). Expression is controlled by transcription factors (TFs) that bind to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to messenger RNA. Interactions result in biological signal control networks. Materials and Methods: Molecular components involved in cSCC were here assembled at abnormally expressed, related and global levels. Networks at these three levels were constructed with corresponding biological factors in term of interactions between miRNAs and target genes, TFs and miRNAs, and host genes and miRNAs. Up/down regulation or mutation of the factors were considered in the context of the regulation and significant patterns were extracted. Results: Participants of the networks were evaluated based on their expression and regulation of other factors. Sub-networks with two core TFs, TP53 and EIF2C2, as the centers are identified. These share self-adapt feedback regulation in which a mutual restraint exists. Up or down regulation of certain genes and miRNAs are discussed. Some, for example the expression of MMP13, were in line with expectation while others, including FGFR3, need further investigation of their unexpected behavior. Conclusions: The present research suggests that dozens of components, miRNAs, TFs, target genes and host genes included, unite as networks through their regulation to function systematically in human cSCC. Networks built under the currently available sources provide critical signal controlling pathways and frequent patterns. Inappropriate controlling signal flow from abnormal expression of key TFs may push the system into an incontrollable situation and therefore contributes to cSCC development.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1675-1679
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• 2014

Objectives: MicroRNAs (miRNAs) are important regulators of many physiological and pathological processes, including tumorigenesis and metastasis. In this study, we sought to determine the underlying molecular mechanisms of metastatic cervical carcinoma by performing miRNA profiling. Methods: Tissue samples were collected from ten cervical squamous cancer patients who underwent hysterectomy and pelvic lymph node (PLN) dissection in our hospital, including four PLN-positive (metastatic) cases and six PLN-negative (non-metastatic) cases. A miRNA microarray platform with 1223 probes was used to determine the miRNA expression profiles of these two tissue types and case groups. MiRNAs having at least 4-fold differential expression between PLN-positive and PLN-negative cervical cancer tissues were bioinformatically analyzed for target gene prediction. MiRNAs with tumor-associated target genes were validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results: Thirty-nine miRNAs were differentially expressed (>4-fold) between the PLN-positive and PLN-negative groups, of which, 22 were up-regulated and 17 were down-regulated. Sixty-nine percent of the miRNAs (27/39) had tumor-associated target genes, and the expression levels of six of those (miR-126, miR-96, miR-144, miR-657, miR-490-5p, and miR-323-3p) were confirmed by quantitative (q)RT-PCR. Conclusions: Six MiRNAs with predicted tumor-associated target genes encoding proteins that are known to be involved in cell adhesion, cytoskeletal remodeling, cell proliferation, cell migration, and apoptosis were identified. These findings suggest that a panel of miRNAs may regulate multiple and various steps of the metastasis cascade by targeting metastasis-associated genes. Since these six miRNAs are predicted to target tumor-associated genes, it is likely that they contribute to the metastatic potential of cervical cancer and may aid in prognosis or molecular therapy.

• International Journal of Oral Biology
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• v.36 no.4
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• pp.179-185
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• 2011

MicroRNAs (miRNAs) are small non-coding RNAs that mediate gene expression at the post-transcriptional level by degrading or repressing targeted mRNAs. These molecules are about 21-25 nucleotides in length and exert their effects by binding to partially complementary sites in mRNAs, predominantly in the 3'-untranslated region (3'-UTR). Recent evidence has demonstrated that miRNAs can function as oncogenes or tumor suppressors through the modulation of multiple oncogenic cellular processes in cancer development, including initiation, cell proliferation, apoptosis, invasion and metastasis. In our present study, we examined the expression profile of miRNAs related to oral cancer cell growth inhibition using normal human oral keratinocytes (NHOK) and YD-38 human oral cancer cells. By miRNA microassay analysis, 40 and 31 miRNAs among the 1,769 examined were found to be up- and down-regulated in YD-38 cells compared with NHOK cells, respectively. Using qRT-PCR analysis, the expression levels of miR-30a and miR-1246 were found to be increased in YD-38 cells compared with NHOK cells, whereas miR-203 and miR-125a were observed to be decreased. Importantly, the overexpression of miR-203 and miR-125a significantly inhibited the growth of YD-38 cells. This finding and the microarray data indicate the involvement of specific miRNAs in the development and progression of oral cancer.

• Journal of Periodontal and Implant Science
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• v.51 no.6
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• pp.386-397
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• 2021

Purpose: MicroRNAs (miRNAs) are epigenetic post-transcriptional regulators that modulate gene expression and have been identified as biomarkers for several diseases, including cancer. This study aimed to systematically review the relationship between miRNAs and periodontal disease in humans, and to evaluate the potential of miRNAs as diagnostic and prognostic biomarkers of disease. Methods: The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (reference number CRD42020180683). The MEDLINE, Scopus, Cochrane Library, Embase, Web of Science, and SciELO databases were searched for clinical studies conducted in humans investigating periodontal diseases and miRNAs. Expression levels of miRNAs across the different groups were analysed using the collected data. Results: A total of 1,299 references were identified in the initial literature search, and 23 articles were finally included in the review. The study designs were heterogeneous, which prevented a meta-analysis of the data. Most of the studies compared miRNA expression levels between patients with periodontitis and healthy controls. The most widely researched miRNA in periodontal diseases was miR-146a. Most studies reported higher expression levels of miR-146a in patients with periodontitis than in healthy controls. In addition, many studies also focused on identifying target genes of the differentially expressed miRNAs that were significantly related to periodontal inflammation. Conclusions: The results of the studies that we analysed are promising, but diagnostic tests are needed to confirm the use of miRNAs as biomarkers to monitor and aid in the early diagnosis of periodontitis in clinical practice.

• Genomics & Informatics
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• v.20 no.2
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• pp.20.1-20.13
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• 2022

Recent studies have focused on the early detection of ovarian cancer (OC) using tumor materials by liquid biopsy. The mechanisms of microRNAs (miRNAs) to impact OC and signaling pathways are still unknown. This study aims to reliably perform functional analysis of previously validated circulating miRNAs' target genes by using pathfindR. Also, overall survival and pathological stage analyses were evaluated with miRNAs' target genes which are common in the The Cancer Genome Atlas and GTEx datasets. Our previous studies have validated three downregulated miRNAs (hsa-miR-885-5p, hsa-miR-1909-5p, and hsa-let7d-3p) having a diagnostic value in OC patients' sera, with high-throughput techniques. The predicted target genes of these miRNAs were retrieved from the miRDB database (v6.0). Active-subnetwork-oriented Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted by pathfindR using the target genes. Enrichment of KEGG pathways assessed by the analysis of pathfindR indicated that 24 pathways were related to the target genes. Ubiquitin-mediated proteolysis, spliceosome and Notch signaling pathway were the top three pathways with the lowest p-values (p < 0.001). Ninety-three common genes were found to be differentially expressed (p < 0.05) in the datasets. No significant genes were found to be significant in the analysis of overall survival analyses, but 24 genes were found to be significant with pathological stages analysis (p < 0.05). The findings of our study provide in-silico evidence that validated circulating miRNAs' target genes and enriched pathways are related to OC and have potential roles in theranostics applications. Further experimental investigations are required to validate our results which will ultimately provide a new perspective for translational applications in OC management.

• Genomics & Informatics
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• v.18 no.4
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• pp.36.1-36.9
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• 2020

Since lung cancer is a major causative for cancer-related deaths, the investigations for discovering biomarkers to diagnose at an early stage and to apply therapeutic strategies have been continuously conducted. Recently, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are being exponentially studied as promising biomarkers of lung cancer. Moreover, supportive evidence provides the competing endogenous RNA (ceRNA) network between lncRNAs and miRNAs participating in lung tumorigenesis. This review introduced the oncogenic or tumor-suppressive roles of lncRNAs and miRNAs in lung cancer cells and summarized the involvement of the lncRNA/miRNA ceRNA networks in carcinogenesis and therapeutic resistance of lung cancer.

• Bulletin of Food Technology
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• v.22 no.1
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• pp.89-95
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• 2009

• Development and Reproduction
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• v.15 no.4
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• pp.331-338
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• 2011

MicroRNAs (miRNAs) function as a key regulator of diverse cellular functions. To find out novel miRNAs that promote the differentiation of mouse embryonic stem cells (mESCs), we compared the miRNAs expression profiles of mESCs under self-renewal vs. differentiation states. We noticed that miR-222 was highly expressed during the differentiation of mESCs. Quantitative RT-PCR analysis revealed that expression of miR-222 was up-regulated during the embryonic bodies formation and retinoic acid -dependent differentiation. When miR-222 was suppressed by antogomiR-222, the differentiation of mESCs was delayed compared to control. Self-renewal marker expression or cell proliferation was not affected but the expression of lineage specific marker was suppressed by the treatment of miR-222 inhibitor during the differentiation of mESCs. Taken together, these results suggest that miR-222 functions to promote the differentiation of mESCs by regulating expression of differentiation related genes.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.7
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• pp.1037-1047
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• 2017

Objective: Despite an increasing number of investigations into the pathophysiology of necrotic enteritis (NE) disease, etiology of NE-associated diseases, and gene expression profiling of NE-affected tissues, the microRNA (miRNA) profiles of NE-affected poultry have been poorly studied. The aim of this study was to induce NE disease in the genetically disparate Fayoumi chicken lines, and to perform non-coding RNA sequencing in the intestinal mucosal layer. Methods: NE disease was induced in the Fayoumi chicken lines (M5.1 and M15.2), and non-coding RNA sequencing was performed in the intestinal mucosal layer of both NE-affected and uninfected chickens to examine the differential expression of miRNAs. Next, quantitative real-time polymerase chain reaction (real-time qPCR) was performed to further examine four miRNAs that showed the highest fold differences. Finally, bioinformatics analyses were performed to examine the four miRNAs target genes involvement in the signaling pathways, and to examine their interaction. Results: According to non-coding RNA sequencing, total 50 upregulated miRNAs and 26 downregulated miRNAs were detected in the NE-induced M5.1 chickens. While 32 upregulated miRNAs and 11 downregulated miRNAs were detected in the NE-induced M15.2 chickens. Results of real-time qPCR analysis on the four miRNAs (gga-miR-9-5p, gga-miR-20b-5p, ggamiR-196-5p, and gga-let-7d) were mostly correlated with the results of RNAseq. Overall, ggamiR-20b-5p was significantly downregulated in the NE-induced M5.1 chickens and this was associated with the upregulation of its top-ranking target gene, mitogen-activated protein kinase, kinase 2. Further bioinformatics analyses revealed that 45 of the gene targets of gga-miR-20b-5p were involved in signal transduction and immune system-related pathways, and 35 of these targets were predicted to interact with each other. Conclusion: Our study is a novel report of miRNA expression in Fayoumi chickens, and could be very useful in understanding the role of differentially expressed miRNAs in a NE disease model.

• Tuberculosis and Respiratory Diseases
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• v.67 no.5
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• pp.413-421
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• 2009

Background: MicroRNAs (miRNAs) play an important role in the regulation of cell proliferation, apoptosis, development and differentiation. Several studies have shown that aberrant expression of miRNAs is involved in cancer development and progression by regulating the expression of proto-oncogenes or tumor suppressor genes. In this study, we investigated miRNA expression profiles in Korean patients with non-small cell lung cancer (NSCLC). Methods: We performed miRNA microarray analysis containing 60~65 bp oligonucleotide probes representing human 318 miRNAs and validated the results of the microarray with Northern blot analysis or quantitative RT-PCR. Next, we examined the correlation between miRNA expression and the target gene transcriptional profile using a human whole-genome-expression microarray. Results: We showed that 35 miRNAs were expressed differentially in the NSCLCs and corresponding non-malignant lung tissues. We showed that 35 miRNAs were expressed differentially in the NSCLCs and corresponding nonmalignant lung tissues. Thirteen of the 35 differentially expressed miRNAs were newly identified in the present study. Of the 35 miRNAs, 2 (miR-371 and miR-210) were over-expressed in lung cancers, and 33 miRNAs, including miR-145, were under-expressed in lung cancers. miR-99b expression consistently showed a negative correlation with FGFR3 expression. Conclusion: Albeit a small number of patients were examined, these results suggest that miRNA expression profiles in Korean lung cancers may be somewhat different from the expression profiles reported on lung cancers in Western populations. The findings suggest that miR-99b might be a tumor suppressor through its up-regulation of FGFR3.