Midie Xu

Bio: Midie Xu is an academic researcher from Fudan University. The author has contributed to research in topics: Metastasis & Medicine. The author has an hindex of 23, co-authored 56 publications receiving 1703 citations. Previous affiliations of Midie Xu include Second Military Medical University.

The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5.

Abstract: The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been reported to be overexpressed in colorectal cancer (CRC) However, its underlying mechanisms in the progression of CRC have not been well studied To investigate the clinical significance of NEAT1, we analyzed its expression levels in a publicly available dataset and in 71 CRC samples from Fudan University Shanghai Cancer Center Functional assays, including the CCK8, EdU, colony formation, wound healing, and Transwell assays, were used to determine the oncogenic role of NEAT1 in human CRC progression Furthermore, RNA pull-down, mass spectrometry, RNA immunoprecipitation, and Dual-Luciferase Reporter Assays were used to determine the mechanism of NEAT1 in CRC progression Animal experiments were used to determine the role of NEAT1 in CRC tumorigenicity and metastasis in vivo NEAT1 expression was significantly upregulated in CRC tissues compared with its expression in normal tissues Altered NEAT1 expression led to marked changes in proliferation, migration, and invasion of CRC cells both in vitro and in vivo Mechanistically, we found that NEAT1 directly bound to the DDX5 protein, regulated its stability, and sequentially activated Wnt signaling Our study showed that NEAT1 indirectly activated the Wnt/β-catenin signaling pathway via DDX5 and fulfilled its oncogenic functions in a DDX5-mediated manner Clinically, concomitant NEAT1 and DDX5 protein levels negatively correlated with the overall survival and disease-free survival of CRC patients Our findings indicated that NEAT1 activated Wnt signaling to promote colorectal cancer progression and metastasis The NEAT1/DDX5/Wnt/β-catenin axis could be a potential therapeutic target of pharmacological strategies

A Positive Feedback Loop of lncRNA-PVT1 and FOXM1 Facilitates Gastric Cancer Growth and Invasion.

Abstract: Purpose: The long, noncoding RNA (lncRNA) PVT1 is an important epigenetic regulator with a critical role in human tumors. Here, we aimed to investigate the clinical application and the potential molecular mechanisms of PVT1 in gastric cancer tumorigenesis and progression.Experimental Design: The expression level of PVT1 was determined by RT-qPCR analysis in 190 pairs of gastric cancer tissues and adjacent normal gastric mucosa tissues (ANT). The biologic functions of PVT1 were assessed by in vitro and in vivo functional experiments. RNA protein pull-down assays and LS/MS mass spectrometry analysis were performed to detect and identify the PVT1- interacting protein FOXM1. Protein-RNA immunoprecipitation assays were conducted to examine the interaction of FOXM1 and PVT1 Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of FOXM1 on the PVT1 promoter.Results: The lncRNA PVT1 was significantly upregulated in gastric cancer tissues compared with ANTs. High expression of PVT1 predicted poor prognosis in patients with gastric cancer. PVT1 enhanced gastric cancer cell proliferation and invasion in vitro and in vivoPVT1 directly bound FOXM1 protein and increased FOXM1 posttranslationally. Moreover, PVT1 is also a FOXM1-responsive lncRNA, and FOXM1 directly binds to the PVT1 promoter to activate its transcription. Finally, PVT1 fulfilled its oncogenic functions in a FOXM1-mediated manner.Conclusions: Our study suggests that PVT1 promotes tumor progression by interacting with FOXM1. PVT1 may be a valuable prognostic predictor for gastric cancer, and the positive feedback loop of PVT1-FOXM1 could be a therapeutic target in pharmacologic strategies. Clin Cancer Res; 23(8); 2071-80. ©2016 AACR.

Circulating Long RNAs in Serum Extracellular Vesicles: Their Characterization and Potential Application as Biomarkers for Diagnosis of Colorectal Cancer

Abstract: Background:Long non-coding RNA and mRNAs are long RNAs ({greater than or equal to} 200 nucleotides) compared to microRNAs. In blood, long RNAs may be protected by serum extracellular vesicles, such as apoptotic bodies (ABs), microvesicles (MVs), and exosomes (EXOs). They are potential biomarker for identifying cancer. Methods:Sera from 76 pre-operative CRC patients, 76 age- and sex-matched healthy subjects and 20 colorectal adenoma (CA) patients without CRC were collected. We investigate the distribution of long RNAs the three vesicles. Seventy-nine cancer-related long RNA were chosen and detected using quantitative PCR (qPCR). Results: OThe quantity of long RNA have varying distribution among three subtypes of extracellular vesicles in serum. Most mRNAs and lncRNAs genes had higher quantity in EXOs than that in ABs and MVs, while MVs contain lowest quantity. We investigated 79 long RNAs chosen from the The Cancer Genome Atlas (TCGA) and the LncRNADisease database in the sera of healthy patients, and those with colorectal cancer (CRC). In the training and test sets, the areas under the curves (AUC) were 0.936 and 0.877 respectively. The AUC of total serum RNA was lower (0.857) than that of exosomal RNA in the same samples (0.936). Conclusions:The present study shows that exosomal mRNAs and lncRNAs in serum could be used as biomarkers to detect CRC. Impact:Among three types of vesicles in sera, EXOs were the richest reservoir for almost all measured long RNAs. the combination of 2 mRNAs, KRTAP5-4, MAGEA3, and 1 lncRNA, BCAR4 could be potential candidates to detect colorectal cancer.

Circulating CUDR, LSINCT-5 and PTENP1 long noncoding RNAs in sera distinguish patients with gastric cancer from healthy controls

Abstract: The examination of circulating nucleic acids (CNAs) is an emerging noninvasive diagnostic technique. However, it is unclear if serum long noncoding RNAs (lncRNAs) represent a novel marker to detect gastric cancer (GC). In this study, we measured 39 candidate cancer-associated lncRNAs by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) in sera from 110 patients with GC, 106 age- and sex-matched healthy subjects and 15 patients with gastric peptic ulcer, markers were validated and assessed by RT-qPCR. The correlation of the expression levels of the candidate serum lncRNAs with clinical parameters of GC patients was performed. A three-lncRNA signature, including CUDR, LSINCT-5 and PTENP1, was identified that may be potential diagnostic marker for GC. The areas under the receiver operating characteristic (ROC) curve for this serum three-lncRNA signature were 0.920 and 0.829 for the two sets of serum samples. Moreover, a risk model for the serum three-lncRNA signature demonstrated that healthy samples can be distinguished from early GC samples. Three-lncRNA signature in serum was identified as diagnostic marker for GC. This work may facilitate the detection of GC and serve as the basis for further studies of the clinical value of serum lncRNAs in maintaining surveillance and forecasting prognosis.

Low expression of LOC285194 is associated with poor prognosis in colorectal cancer

Abstract: The long non-coding RNAs (lncRNAs) study has gradually become one of the hot topics in the field of RNA biology. One lncRNA which has attracted attention is LOC285194, a lncRNA demonstrated the potential tumor-suppressor role in osteosarcoma. The aim of this study was to examine the expression of LOC285194 in colorectal cancer (CRC) patients and to investigate the relationship between this lncRNA levels and existing clinicopathologic parameters and patient survival. The expression of LOC285194 was detected by quantitative real-time polymerase chain reaction in pairs of tumorous and adjacent normal tissues of 81 colorectal cancer patients with a follow-up of 5 years, as well as in three colorectal cancer cell lines and normal intestinal mucous cell line. Then, we analyzed the potential relationship between this lncRNA levels in tumor tissues and existing clinicopathological features of CRC, and clinical outcome. The relative expression levels of LOC285194 was significantly lower in tumor tissues (p < 0.001) and colorectal cancer cell lines compared with adjacent normal tissues and normal intestinal mucous cell line. In addition, low expression of LOC285194 was correlated with larger tumor size (p = 0.015), higher tumor stage (p = 0.034), and more distant metastasis (p = 0.046). Kaplan-Meier analysis indicated that patients with low LOC285194 expression had a poor disease free survival (p = 0.010). Moreover, multivariate analysis showed that decreased expression of LOC285194 was an independent predictor of disease-specific survival. Our data indicate that LOC285194 might be a novel prognostic indicator in colorectal cancer and may be a potential target for diagnosis and gene therapy.

Long Noncoding RNA and Cancer: A New Paradigm.

Abstract: In addition to mutations or aberrant expression in the protein-coding genes, mutations and misregulation of noncoding RNAs, in particular long noncoding RNAs (lncRNA), appear to play major roles in cancer. Genome-wide association studies of tumor samples have identified a large number of lncRNAs associated with various types of cancer. Alterations in lncRNA expression and their mutations promote tumorigenesis and metastasis. LncRNAs may exhibit tumor-suppressive and -promoting (oncogenic) functions. Because of their genome-wide expression patterns in a variety of tissues and their tissue-specific expression characteristics, lncRNAs hold strong promise as novel biomarkers and therapeutic targets for cancer. In this article, we have reviewed the emerging functions and association of lncRNAs in different types of cancer and discussed their potential implications in cancer diagnosis and therapy. Cancer Res; 77(15); 3965-81. ©2017 AACR.

A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response

Abstract: Recently, more than 1000 large intergenic noncoding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediates apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulate their localization to sets of previously active genes.

MicroRNAs in metabolism and metabolic disorders.

Abstract: MicroRNAs (miRNAs) have recently emerged as key regulators of metabolism. For example, miR-33a and miR-33b have a crucial role in controlling cholesterol and lipid metabolism in concert with their host genes, the sterol-regulatory element-binding protein (SREBP) transcription factors. Other metabolic miRNAs, such as miR-103 and miR-107, regulate insulin and glucose homeostasis, whereas miRNAs such as miR-34a are emerging as key regulators of hepatic lipid homeostasis. The discovery of circulating miRNAs has highlighted their potential as both endocrine signalling molecules and disease markers. Dysregulation of miRNAs may contribute to metabolic abnormalities, suggesting that miRNAs may potentially serve as therapeutic targets for ameliorating cardiometabolic disorders.

Extracellular vesicles in cancer - implications for future improvements in cancer care.

Abstract: The sustained growth, invasion, and metastasis of cancer cells depend upon bidirectional cell-cell communication within complex tissue environments. Such communication predominantly involves the secretion of soluble factors by cancer cells and/or stromal cells within the tumour microenvironment (TME), although these cell types have also been shown to export membrane-encapsulated particles containing regulatory molecules that contribute to cell-cell communication. These particles are known as extracellular vesicles (EVs) and include species of exosomes and shed microvesicles. EVs carry molecules such as oncoproteins and oncopeptides, RNA species (for example, microRNAs, mRNAs, and long non-coding RNAs), lipids, and DNA fragments from donor to recipient cells, initiating profound phenotypic changes in the TME. Emerging evidence suggests that EVs have crucial roles in cancer development, including pre-metastatic niche formation and metastasis. Cancer cells are now recognized to secrete more EVs than their nonmalignant counterparts, and these particles can be isolated from bodily fluids. Thus, EVs have strong potential as blood-based or urine-based biomarkers for the diagnosis, prognostication, and surveillance of cancer. In this Review, we discuss the biophysical properties and physiological functions of EVs, particularly their pro-metastatic effects, and highlight the utility of EVs for the development of cancer diagnostics and therapeutics.