Integrated miRNA profiling and bioinformatics analyses reveal upregulated miRNAs in gastric cancer

Yuan, Chiun‐Jye; Zhang, Yue; Tu, Wenwen; Guo, Yusheng

doi:10.3892/ol.2019.10495

Cited by 22 publications

(25 citation statements)

References 40 publications

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“…However, the potential association between the miR-15b family and GC is controversial. miR-15b has been shown to be downregulated in SGC7901/DDP cells [46] and gastric adenoma [47], while Yuan et al [48] has shown the significant overexpression of miR-15b in GC, which was found by analyzing 1000 GC samples included in four public datasets. In addition, miR-15b-5p impact on invasion, migration and proliferation of GC cells with high miR-15b-5p levels in GC cell lines, tissues and serum samples were confirmed by Zhao et al [49].…”

Section: Discussionmentioning

confidence: 99%

Exosomal transfer of miR-15b-3p enhances tumorigenesis and malignant transformation through the DYNLT1/Caspase-3/Caspase-9 signaling pathway in gastric cancer

Wei

Peng

Yang

et al. 2020

J Exp Clin Cancer Res

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Background: Exosomes are essential for tumor growth, metastasis, and are used as novel signaling molecules in targeted therapies. Therefore, exosomal miRNAs can be used in new diagnostic and therapeutic approaches due to their involvement in the development of cancers. However, the detailed biological function, potential molecular mechanism and clinical application of exo-miR-15b-3p in gastric cancer (GC) remains unclear.Methods: miR-15b-3p mRNA levels in tissues, serum, cells and exosomes were analyzed using qRT-PCR assays. qRT-PCR, immunohistochemical and western blotting analyses were utilized for the determination of DYNLT1 expression. The interrelationship connecting miR-15b-3p with DYNLT1 was verified using Dual-luciferase report, western blotting and qRT-PCR assays. Fluorescent PKH-26 or GFP-Lv-CD63 labeled exosomes, as well as Cy3-miR-15b-3p, were utilized to determine the efficacy of the transfer of exo-miR-15b-3p between BGC-823 and recipient cells. Several in vitro assays and xenograft tumor models were conducted to determine exo-miR-15b-3p impact on GC progression.Results: This is the first study to confirm high miR-15b-3p expression in GC cell lines, tissues and serum. Exosomes obtained from 108 GC patient serum samples and GC cell-conditioned medium were found to show upregulation of exo-miR-15b-3p, with the area under the ROC curve (AUC) being 0.820 [0.763-0.876], which is superior to the AUC of tissues and serum miR-15b-3p (0.674 [0.600-0.748] and 0.642 [0.499-0.786], respectively). In addition, high exo-miR-15b-3p expression in serum was found to accurately predict worse overall survival. SGC-7901 and GES-1 cells are capable of internalizing BGC-823 cell-derived exosomes, allowing the transfer of miR-15b-3p. Migration, invasion, proliferation and inhibition of apoptosis in vitro and in vivo were enhanced by exo-miR-15b-3p, by restraining DYNLT1, Cleaved Caspase-9 and Caspase-3 expression.Conclusions: This study identified a previously unknown regulatory pathway, exo-miR-15b-3p/DYNLT1/Caspase-3/ Caspase-9, which promotes GC development and GES-1 cell malignant transformation. Therefore, serum exo-miR-15b-3p may be a potential GC diagnosis and prognosis biomarker, which can be used in precise targeted GC therapy.

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Section: Discussionmentioning

confidence: 99%

Exosomal transfer of miR-15b-3p enhances tumorigenesis and malignant transformation through the DYNLT1/Caspase-3/Caspase-9 signaling pathway in gastric cancer

Wei

Peng

Yang

et al. 2020

J Exp Clin Cancer Res

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“…MiRNAs are a class of naturally occurring small noncoding RNAs which are 19-25 nucleotides (19-25 nt) in length. They have recently been reported to be frequently dysregulated in various cancers [4][5][6][7] . Accumulating evidences indicate that circulating miRNAs could be stable blood-based markers for cancer diagnosis 8 .…”

Section: Serum Micrornas (Mirnas) Have Been Reported As Novel Biomarkmentioning

confidence: 99%

Identification of non-invasive biomarkers for predicting the radiosensitivity of nasopharyngeal carcinoma from serum microRNAs

Zhu

et al. 2020

Sci Rep

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Serum microRNAs (miRNAs) have been reported as novel biomarkers for various diseases. But circulating biomarkers for predicting the radiosensitivity of nasopharyngeal carcinoma (NPC) have not been used in clinical practice. To screen out of differently expressed serum miRNAs from NPC patients with different radiosensitivity may be helpful for its individual therapy. NPC patients with different radiosensitivity were enrolled according to the inclusion and exclusion criteria. RNA was isolated from serum of these NPC patients before treatment. We investigated the differential miRNA expression profiles using microarray test (GSE139164), and the candidate miRNAs were validated by reverse transcription-quantitative real time polymerase chain reaction (RT-qPCR) experiments. Receiver operating characteristic (ROC) analysis has been applied to estimate the diagnostic value. In this study, 37 serum-specific miRNAs were screened out from 12 NPC patients with different radiosensitivity by microarray test. Furthermore, RT-qPCR analysis confirmed that hsa-miR-1281 and hsa-miR-6732-3p were significantly downregulated in the serum of radioresistant NPC patients (P < 0.05), which was consistent with the results of microarray test. ROC curves demonstrated that the AUC for hsa-miR-1281 was 0.750 (95% CI: 0.574–0.926, SE 87.5%, SP 57.1%). While the AUC for hsa-miR-6732-3p was 0.696 (95% CI: 0.507–0.886, SE 56.3%, SP 78.6%). These results suggested that hsa-miR-1281 and hsa-miR-6732-3p in serum might serve as potential biomarkers for predicting the radiosensitivity of NPC.

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“…miRNAs (or microRNAs or miRs) are small non-coding RNAs which regulate gene expression at the post-transcriptional level by inhibiting the stability or the transcriptional efficiency of target genes. Through their action of regulating the genome, miRNAs are key players in many physiopathological mechanisms, particularly cancers ( He and Hannon, 2004 ; Yuan et al, 2019 ). To identify if miRNAs are involved in the modification of MEC features, we performed miRNA expression profiling analyses on the MECs co-cultured either with hASCs or MAs.…”

Section: Resultsmentioning

confidence: 99%

The Adipose Microenvironment Dysregulates the Mammary Myoepithelial Cells and Could Participate to the Progression of Breast Cancer

Delort

Cholet

Decombat

et al. 2021

Front. Cell Dev. Biol.

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Breast cancer is the most common cancer among women worldwide. Overweight and obesity are now recognized as established risk factors for this pathology in postmenopausal women. These conditions are also believed to be responsible for higher recurrence and mortality rates. Reciprocal interactions have been described between adipose and cancer cells. An adipose microenvironment favors a greater proliferation of cancer cells, their invasion and even resistance to anti-cancer treatments. In addition, the chronic low-grade inflammation observed in obese individuals is believed to amplify these processes. Among the cell types present in the breast, myoepithelial cells (MECs), located at the interface of the epithelial cells and the stroma, are considered “tumor suppressor” cells. During the transition from ductal carcinoma in situ to invasive cancer, disorganization or even the disappearance of MECs is observed, thereby enhancing the ability of the cancer cells to migrate. As the adipose microenvironment is now considered as a central actor in the progression of breast cancer, our objective was to evaluate if it could be involved in MEC functional modifications, leading to the transition of in situ to invasive carcinoma, particularly in obese patients. Through a co-culture model, we investigated the impact of human adipose stem cells from women of normal weight and obese women, differentiated or not into mature adipocytes, on the functionality of the MECs by measuring changes in viability, apoptosis, gene, and miRNA expressions. We found that adipose cells (precursors and differentiated adipocytes) could decrease the viability of the MECs, regardless of the original BMI. The adipose cells could also disrupt the expression of the genes involved in the maintenance of the extracellular matrix and to amplify the expression of leptin and inflammatory markers. miR-122-5p and miR-132-3p could also be considered as targets for adipose cells. The metabolite analyses revealed specific profiles that may be involved in the growth of neoplastic cells. All of these perturbations could thus be responsible for the loss of tumor suppressor status of MECs and promote the transition from in situ to invasive carcinoma.

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Integrated miRNA profiling and bioinformatics analyses reveal upregulated miRNAs in gastric cancer

Cited by 22 publications

References 40 publications

Exosomal transfer of miR-15b-3p enhances tumorigenesis and malignant transformation through the DYNLT1/Caspase-3/Caspase-9 signaling pathway in gastric cancer

Exosomal transfer of miR-15b-3p enhances tumorigenesis and malignant transformation through the DYNLT1/Caspase-3/Caspase-9 signaling pathway in gastric cancer

Identification of non-invasive biomarkers for predicting the radiosensitivity of nasopharyngeal carcinoma from serum microRNAs

The Adipose Microenvironment Dysregulates the Mammary Myoepithelial Cells and Could Participate to the Progression of Breast Cancer

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