Yicun Wang

Bio: Yicun Wang is an academic researcher from Jilin University. The author has contributed to research in topics: Lung cancer & Cancer. The author has an hindex of 2, co-authored 3 publications receiving 45 citations.

MicroRNA-155, induced by FOXP3 through transcriptional repression of BRCA1, is associated with tumor initiation in human breast cancer.

Abstract: // Song Gao 1, 2, * , Yicun Wang 3, * , Meng Wang 4 , Zhi Li 5 , Zhiying Zhao 6 , Raymond X. Wang 2 , Rong Wu 1 , Zhengwei Yuan 1 , Ranji Cui 3 , Kai Jiao 2, 7 , Lizhong Wang 2, 7 , Ling Ouyang 8 and Runhua Liu 2, 7 1 The Second Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, China 2 Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA 3 Provincial Key Laboratory on Molecular and Chemical Genetic, Second Hospital of Jilin University, Changchun, China 4 Department of Oncology, Cancer Hospital of Harbin Medical University, Harbin, China 5 Department of General Surgery, Henan Cancer Hospital, Zhengzhou, China 6 School of Computer Science and Engineering, Northeastern University, Shenyang, China 7 Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, USA 8 Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, China * These authors have contributed equally to this work Correspondence to: Runhua Liu, email: runhua@uab.edu Ling Ouyang, email: ouyang1964@163.com Keywords: microRNA, breast cancer, plasma, FOXP3, BRCA1 Received: December 10, 2016 Accepted: April 11, 2017 Published: May 11, 2017 ABSTRACT MicroRNA (miR)-155 is upregulated in breast cancer cells and in sera of patients with breast cancer, but its clinical relevance remains uncertain. The objective of the present effort was to address the transcriptional regulation of miR-155. A bioinformatics analysis of public datasets validated upregulation of miR-155 in tumor cells of patients with breast cancer, particularly those who were at early stages and had triple-negative cancers. The expression profiling and clinical relevance of miR-155 in tumor cells and blood cells were characterized by TaqMan miR assays and, in plasma and exosomes, by nest-quantitative PCR analysis. There was a positive correlation between expression of FOXP3 and miR-155 in breast cancer cell lines and primary breast cancers. In breast cancer cells, FOXP3 induced miR-155 through transcriptional repression of BRCA1 . Furthermore, in an Alabama cohort, blood and plasma samples were collected from 259 participants, including patients with breast cancer or benign breast tumors, members of breast cancer families, and matched healthy female controls. For patients with early stage or localized breast cancer, there were high levels of miR-155 in both plasma and blood cells. In cultured breast cancer cells, expression of miR-155 was induced by FOXP3 but was not significantly changed in culture medium or exosomes, suggesting that circulating miR-155 originated from blood cells. These findings reveal a transcriptional axis of FOXP3-BRCA1-miR-155 in breast cancer cells and show that plasma miR-155 may serve as a non-invasive biomarker for detection of early stage breast cancer.

CXCL12 suppresses cisplatin-induced apoptosis through activation of JAK2/STAT3 signaling in human non-small-cell lung cancer cells.

Abstract: AIMS Poor efficacy of chemotherapy drugs in non-small-cell lung cancer (NSCLC) is the key reason for the failure of treatment, but the mechanism of this remains largely unknown. Stromal cell-derived factor 1-alpha (SDF-1α/CXCL12) is a small chemotactic cytokine protein that plays an important role in tumor progression. In this study, we investigated the anti-apoptotic mechanism of the CXCL12/CXCR4 axis in response to cisplatin, a commonly used chemotherapeutic drug, in human lung adenocarcinoma A549 cells. METHODS CXCL12 blocks cisplatin-induced apoptosis in A549, and the results were shown by propidium iodide/annexin V staining in vitro. The mechanism of CXCL12 stimulating phosphorylation of STAT3 through CXCR4/JAK2 was demonstrated by immunofluorescence and Western blotting. The expression of CXCL12 and p-STAT3 in clinical specimens was examined by immunohistochemistry. RESULTS CXCL12 significantly decreased the ratio of apoptotic cells and stimulation of phospho-signal transducer and activator of transcription (p-STAT)-3 in a time-dependent manner through interaction with CXCR4. Among the signaling molecules downstream of CXCR4, the JAK2/STAT3 pathway plays a predominant role in the anti-apoptotic effect of CXCL12. Analysis of clinical specimens revealed that increased CXCL12 and p-STAT3 expression correlates with enhanced lung cancer progression. CONCLUSION These data suggest that CXCR4 contributes to CXCL12-mediated anti-apoptosis by activating JAK2/STAT3 pathway in NSCLC cells. Therefore, targeting CXCL12/CXCR4 signaling pathway reveals a potential therapeutic approach for NSCLC.

Collagen type 1 alpha 1 chain is a novel predictive biomarker of poor progression-free survival and chemoresistance in metastatic lung cancer.

Abstract: Background: Collagen type 1 alpha 1 chain (COL1A1) is an extracellular matrix protein comprising two alpha 1 chains and one alpha 2 chain. Our previous study identified that COL1A1 is the key gene during the development and progression of lung adenocarcinoma by multi-omics analysis. However, the clinical significance of COL1A1 expression in lung cancer samples remains largely unknown. Here, we aimed to evaluate the level of COL1A1 in lung cancer samples and correlate its level with the clinical outcome. Methods: COL1A1 gene expression in lung cancer samples was analyzed using the Oncomine database (www.oncomine.org). A total of 308 lung cancer samples (208 formalin-fixed paraffin-embedded tissues and 100 blood samples) were assessed for protein expression of COL1A1. Immunohistochemistry staining and enzyme-linked immunosorbent assay were used to detect COL1A1 expression in tissues and serum, respectively. Results: We identified an elevation of COL1A1 in mRNA level and gene amplification in lung cancer tissues compared with normal lung tissues. High COL1A1 expression was observed in lung cancer tissues and serum (P < 0.05), it was significantly correlated with the peripheral type tumor, the larger diameter of the tumor, the occurrence of lymph node metastases and distant metastases, a higher TNM stage, and smoking (P < 0.05). High COL1A1 expression was associated with poor progression-free survival (PFS) and chemoresistance in lung cancer patients (P < 0.05). Multivariable Cox-regression analysis showed that COL1A1 expression was an independent prognostic factor (P < 0.05). Furthermore, the area under the receiver operating characteristic (AUC) curve was 0.909 for the combined COL1A1 and carcinoembryonic antigen (CEA) measurement. Conclusion: Our findings revealed that COL1A1 could be used as a novel diagnostic, prognostic, and chemoresistance biomarker of human lung cancer, and these results provide a potential therapeutic strategy for lung cancer patients.

MicroRNAs: Target Recognition and Regulatory Functions

Abstract: MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

The Role of Exosomal MicroRNAs in the Tumor Microenvironment of Breast Cancer.

Abstract: Breast cancer, ranking first among women's cancers worldwide, develops from the breast tissue. Study of the breast tissue is, therefore of great significance to the diagnosis and treatment of breast cancer. Exosomes, acting as an effective communicator between cells, are in the ascendant in recent years. One of the most important cargoes contained in the exosomes is microRNAs, belonging to the non-coding RNA family. When the exosomal microRNAs are absorbed into the intracellular location, most of the microRNAs will act as tumor promoters or suppressors by inhibiting the translation process of the target mRNA, thus affecting the behavior of other stromal cells in the tumor microenvironment. At present, growing research focuses on the different types of donor cell sources, their contribution to cancer, miRNA profiling, their biomarker potential, etc. This review aims to state the function of diverse miRNAs in exosomes medicated cell-cell communication and the potency of some specific enriched miRNAs as molecular markers in clinical trials. We also describe the mechanism of anti-cancer compounds through exosomes and the exploration of artificially engineered techniques that lead miRNA-inhibitors into exosomes for therapeutic use.

Exosomes of pasteurized milk: potential pathogens of Western diseases

Abstract: Milk consumption is a hallmark of western diet. According to common believes, milk consumption has beneficial effects for human health. Pasteurization of cow’s milk protects thermolabile vitamins and other organic compounds including bioactive and bioavailable exosomes and extracellular vesicles in the range of 40–120 nm, which are pivotal mediators of cell communication via systemic transfer of specific micro-ribonucleic acids, mRNAs and regulatory proteins such as transforming growth factor-β. There is compelling evidence that human and bovine milk exosomes play a crucial role for adequate metabolic and immunological programming of the newborn infant at the beginning of extrauterine life. Milk exosomes assist in executing an anabolic, growth-promoting and immunological program confined to the postnatal period in all mammals. However, epidemiological and translational evidence presented in this review indicates that continuous exposure of humans to exosomes of pasteurized milk may confer a substantial risk for the development of chronic diseases of civilization including obesity, type 2 diabetes mellitus, osteoporosis, common cancers (prostate, breast, liver, B-cells) as well as Parkinson’s disease. Exosomes of pasteurized milk may represent new pathogens that should not reach the human food chain.

Extracellular vesicles from triple-negative breast cancer cells promote proliferation and drug resistance in non-tumorigenic breast cells.

Abstract: Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype, is genetically heterogeneous which challenges the identification of clinically effective molecular makers. Extracellular vesicles (EVs) are key players in the intercellular signaling communication and have been shown to be involved in tumorigenesis. The main goal of this study was to evaluate the role and mechanisms of EVs derived from TNBC cells in modulating proliferation and cytotoxicity to chemotherapeutic agents in non-tumorigenic breast cells (MCF10A). EVs were isolated from TNBC cell lines and characterized by nanoparticle tracking analysis, Western blot, and transmission electron microscopy. MCF10A cells were treated with the isolated EVs and evaluated for cell proliferation and cytotoxicity to Docetaxel and Doxorubicin by the MTT and MTS assays, respectively. Gene and miRNA expression profiling was performed in the treated cells to determine expression changes that may be caused by EVs treatment. MCF10A cells treated with HCC1806-EVs (MCF10A/HCC1806-EVs) showed a significant increase in cell proliferation and resistance to the therapeutic agents tested. No significant effects were observed in the MCF10A cells treated with EVs derived from MDA-MB-231 cells. Gene and miRNA expression profiling revealed 138 genes and 70 miRNAs significantly differentially expressed among the MCF10A/HCC1806-EVs and the untreated MCF10A cells, affecting mostly the PI3K/AKT, MAPK, and HIF1A pathways. EVs isolated from the HCC1806 TNBC cells are capable of inducing proliferation and drug resistance on the non-tumorigenic MCF10A breast cells, potentially mediated by changes in genes and miRNAs expression associated with cell proliferation, apoptosis, invasion, and migration.

New emerging roles of microRNAs in breast cancer.

Abstract: MicroRNAs constitute a large family of non-coding RNAs, which actively participate in tumorigenesis by regulating a set of mRNAs of distinct signaling pathways. An altered expression of these molecules has been found in different tumorigenic processes of breast cancer, the most common type of cancer in the female population worldwide. The objective of this review is to discuss how miRNAs become master regulators in breast tumorigenesis. An integrative review of miRNAs and breast cancer literature from the last 5 years was done on PubMed. We summarize recent works showing that the defects on the biogenesis of miRNAs are associated with different breast cancer characteristics. Then, we show several examples that demonstrate the link between cellular processes regulated by miRNAs and the hallmarks of breast cancer. Finally, we examine the complexity in the regulation of these molecules as they are modulated by other non-coding RNAs and the clinical applications of miRNAs as they could serve as good diagnostic and classification tools. The information presented in this review is important to encourage new directed studies that consider microRNAs as a good tool to improve the diagnostic and treatment alternatives in breast cancer.