miR-27a promotes proliferation, migration, and invasion of colorectal cancer by targeting FAM172A and acts as a diagnostic and prognostic biomarker

Liu, Wenjun; Qian, Kai; Xing, Wei; Deng, Haijun; Zhao, Bei; Chen, Qing; Zhang, Jinqian; Liu, Hao

doi:10.3892/or.2017.5592

Cited by 27 publications

(20 citation statements)

References 40 publications

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“…Furthermore, following the growth in MCS, both cell lines exhibited a subset of 16 differentially expressed miRNAs. The significance of our observations is supported by previous reports indicating that miR-200a-3p [39], miR-141-3p [40], miR-375 [41], miR-194-5p [42], miR-27a-3p [43] and miR-29b-3p [42] could be clinically applied as potential CRC biomarkers. In addition, miR-194 was shown as one of the most deregulated miRNAs in cancerous tissue as well as miRNAs of the miR-200 family, including miR-200b and miR-200c [44].…”

Section: Discussionsupporting

confidence: 89%

3D Cell Culture-Based Global miRNA Expression Analysis Reveals miR-142-5p as a Theranostic Biomarker of Rectal Cancer Following Neoadjuvant Long-Course Treatment

et al. 2020

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Altered expression of miRNAs in tumor tissue encourages the translation of this specific molecular pattern into clinical practice. However, the establishment of a selective biomarker signature for many tumor types remains an inextricable challenge. For this purpose, a preclinical experimental design, which could maintain a fast and sensitive discovery of potential biomarkers, is in demand. The present study suggests that the approach of 3D cell cultures as a preclinical cancer model that is characterized to mimic a natural tumor environment maintained in solid tumors could successfully be employed for the biomarker discovery and validation. Subsequently, in this study, we investigated an environment-dependent miRNA expression changes in colorectal adenocarcinoma DLD1 and HT29 cell lines using next-generation sequencing (NGS) technology. We detected a subset of 16 miRNAs differentially expressed in both cell lines cultivated in multicellular spheroids compared to expression levels in cells grown in 2D. Furthermore, results of in silico miRNA target analysis showed that miRNAs, which were differentially expressed in both cell lines grown in MCS, are involved in the regulation of molecular mechanisms implicated in cell adhesion, cell-ECM interaction, and gap junction pathways. In addition, integrins and platelet-derived growth factor receptors were determined to be the most significant target genes of deregulated miRNAs, which was concordant with the environment-dependent gene expression changes validated by RT-qPCR. Our results revealed that 3D microenvironment-dependent deregulation of miRNA expression in CRC cells potentially triggers essential molecular mechanisms predominantly including the regulation of cell adhesion, cell–cell, and cell–ECM interactions important in CRC initiation and development. Finally, we demonstrated increased levels of selected miR-142-5p in rectum tumor tissue samples after neoadjuvant long course treatment compared to miR-142-5p expression levels in tumor biopsy samples collected before the therapy. Remarkably, the elevation of miR-142-5p expression remained in tumor samples compared to adjacent normal rectum tissue as well. Therefore, the current study provides valuable insights into the molecular miRNA machinery of CRC and proposes a potential miRNA signature for the assessment of CRC in further clinical research.

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Section: Discussionsupporting

confidence: 89%

3D Cell Culture-Based Global miRNA Expression Analysis Reveals miR-142-5p as a Theranostic Biomarker of Rectal Cancer Following Neoadjuvant Long-Course Treatment

et al. 2020

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“…Our further studies will focus on this miRNA to throw more light on this difference. miR-27a is one of the least studied miRNAs in the literature (36,37). During our research we found that this miRNA showed very similar behavior both in meso-and hypopharyngeal carcinomas as miR-21.…”

Section: Discussionsupporting

confidence: 59%

Comparative miRNA Expression Profile Analysis of Squamous Cell Carcinoma and Peritumoral Mucosa from the Meso- and Hypopharynx

Orosz

Gombos

Riedling³

et al. 2017

CGP

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Abstract. Background In Europe, according to the age-standardized rates per 100,000 population, Hungary had the highest estimated incidence, mortality and prevalence in lip, oral cavity and pharyngeal cancers for both sexes. Based on the cancer registerty held by the National Institute of Oncology, in 2010 and 2011 meso-and hypopharyngeal carcinomas counted more than 1,200 cases. The number of diagnosed mesopharyngeal carcinomas in our clinical site has doubled, while hypopharyngeal carcinoma cases have tripled since 1983 (Figures 1 and 2). Incidence of meso-and hypopharyngeal carcinomas is constantly growing, while the rate of mortality is above 50% due to late-stage recognition. In our clinical practice, malignant cancers of the meso-and hypopharyngeal regions are most specific in the 55-60 age range population, although the appearance of the different pharyngeal carcinomas has been observed in a growing number at younger ages in the past few years. It is important to note that the cancers affecting only one region, having good operability options and a better prognosis are disappearing, while the ones involving more than one region, with aggressive spreading and progressive prognosis are becoming more frequent. Our goal was to find and study a molecular marker that could be used as a predictive and a prognostic tool to complete clinical diagnostics.In recent years micro-RNAs (miRNA) have been excessively studied. These small, 19-25 base-pair-long RNAs are transcribed from an intra-or intergenic segment of DNA and are not translated into proteins. Matured miRNA binds to a ribonucleotid complex, called RISC (RNA induced silencing complex), and drives the regulation of mRNA translation, either by binding to the target mRNA's 3' UTR (untranslated region) segment, or to 5' UTR or just directly to the ORF (open reading frame). This way translation is blocked or endonucleases are activated causing the degradation of mRNA target (1, 2). An estimated 50-60% of the human genome is regulated by miRNAs. A specific mRNA can be regulated by multiple miRNAs, and a miRNA can modulate translation of more then hundred mRNAs (1). This RNA interference mechanism establishes precise modulation of gene expression, harmonic regulation of cellular functions as cell division, differentiation, apoptosis and intermediary metabolism (3). miRNAs can behave either as oncogenes (oncomirs) or tumor suppressors according to which target mRNA is regulated by them (1). miRNAs can be detected in blood serum, saliva and other body fluids (4-285

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“…Data from GSE39833 showed that both circulating exosomal miR-27a and miR-130a were potential diagnostic biomarkers for colorectal cancer, which was validated in our subsequent experiments. Liu and colleagues revealed that miR-27a promotes proliferation, migration, and invasion of colorectal cancer by targeting FAM172A (30). Chen and colleagues demonstrated that miR-130a is upregulated in colorectal cancer and promotes cell growth and motility by directly targeting forkhead box F2 (FOXF2; ref.…”

Section: Discussionmentioning

confidence: 99%

Circulating Exosomal miR-27a and miR-130a Act as Novel Diagnostic and Prognostic Biomarkers of Colorectal Cancer

Liu

Pan

Sun

et al. 2018

Cancer Epidemiology, Biomarkers &Amp; Prevention

108

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Colorectal cancer is one of the most common cancers worldwide usually is associated with poor prognosis due to the advanced stage when diagnosed. This study aimed to investigate whether specific circulating exosomal miRNAs could act as biomarkers for early diagnosis of colorectal cancer. A total of 369 peripheral blood samples were included in this study. In the discovery phase, circulating exosomal miR-27a and miR-130a were selected after synthetical analysis of two GEO datasets and TCGA database. The differential expression and diagnostic utility of miR-27a and miR-130a panel were validated using qRT-PCR and ROC curve analysis in subsequent training phase, validation phase, and external validation phase. The prognosis of circulating exosomal miR-27a and miR-130a were investigated using the Kaplan-Meier method. The expression of exosomal miR-27a and miR-130a in plasma significantly increased in colorectal cancer. The area under ROC curves (AUC) of miR-27a (miR-130a) were 0.773 (0.742) in the training phase, 0.82 (0.787) in the validation phase, and 0.746 (0.697) in the external validation phase. The combination of two miRNAs presented higher diagnostic utility for colorectal cancer (AUCs = 0.846, 0.898, and 0.801 for the training, validation, and external validation phases, respectively). Patients with colorectal cancer with high expression of circulating exosomal miR-27a or miR-130a underwent poorer prognosis. We identified a circulating exosomal miRNAs panel for the detection of colorectal cancer. The exosomal miR-27a and miR-130a panel in plasma may act as a noninvasive biomarker for early detection and predicting prognosis of colorectal cancer. .

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miR-27a promotes proliferation, migration, and invasion of colorectal cancer by targeting FAM172A and acts as a diagnostic and prognostic biomarker

Cited by 27 publications

References 40 publications

3D Cell Culture-Based Global miRNA Expression Analysis Reveals miR-142-5p as a Theranostic Biomarker of Rectal Cancer Following Neoadjuvant Long-Course Treatment

3D Cell Culture-Based Global miRNA Expression Analysis Reveals miR-142-5p as a Theranostic Biomarker of Rectal Cancer Following Neoadjuvant Long-Course Treatment

Comparative miRNA Expression Profile Analysis of Squamous Cell Carcinoma and Peritumoral Mucosa from the Meso- and Hypopharynx

Circulating Exosomal miR-27a and miR-130a Act as Novel Diagnostic and Prognostic Biomarkers of Colorectal Cancer

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