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Author

Fei Guo

Bio: Fei Guo is an academic researcher from University of Texas MD Anderson Cancer Center. The author has contributed to research in topics: Epithelial–mesenchymal transition & Radiology. The author has an hindex of 3, co-authored 3 publications receiving 196 citations. Previous affiliations of Fei Guo include Tianjin Medical University General Hospital.

Papers
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Journal ArticleDOI
TL;DR: The post-transcriptional regulatory network that is involved in EMT and MET is discussed and how targeting E MT and MET may provide effective therapeutics for human disease is discussed.
Abstract: Epithelial-to-mesenchymal transition (EMT) and its reverse process, mesenchymal-to-epithelial transition (MET), play important roles in embryogenesis, stem cell biology, and cancer progression. EMT can be regulated by many signaling pathways and regulatory transcriptional networks. Furthermore, post-transcriptional regulatory networks regulate EMT; these networks include the long non-coding RNA (lncRNA) and microRNA (miRNA) families. Specifically, the miR-200 family, miR-101, miR-506, and several lncRNAs have been found to regulate EMT. Recent studies have illustrated that several lncRNAs are overexpressed in various cancers and that they can promote tumor metastasis by inducing EMT. MiRNA controls EMT by regulating EMT transcription factors or other EMT regulators, suggesting that lncRNAs and miRNA are novel therapeutic targets for the treatment of cancer. Further efforts have shown that non-coding-mediated EMT regulation is closely associated with epigenetic regulation through promoter methylation (e.g., miR-200 or miR-506) and protein regulation (e.g., SET8 via miR-502). The formation of gene fusions has also been found to promote EMT in prostate cancer. In this review, we discuss the post-transcriptional regulatory network that is involved in EMT and MET and how targeting EMT and MET may provide effective therapeutics for human disease.

117 citations

Journal ArticleDOI
TL;DR: The findings showed thatmiR-101 represents a redundant mechanism for the miR-200 family that regulates EMT through two major E-cadherin transcriptional repressors and inhibited EMT and cell migration and invasion.
Abstract: Ovarian carcinoma is the most lethal gynecologic malignancy; the majority of patients succumb to the disease within 5 years of diagnosis. The poor survival rate is attributed to diagnosis at advanced stage, when the tumor has metastasized. The epithelial-to-mesenchymal transition (EMT) is a necessary step toward metastatic tumor progression. Through integrated computational analysis, we recently identified a master microRNA (miRNA) network that includes miR-101 and regulates EMT in ovarian carcinoma. In the present study, we characterized the functions of miR-101. Using reporter gene assays, we demonstrated that miR-101 suppressed the expression of the E-cadherin repressors ZEB1 and ZEB2 by directly targeting the 3'-untranslated region (3'UTR) of both ZEB1 and ZEB2. Introduction of miR-101 significantly inhibited EMT and cell migration and invasion. Introducing cDNAs of ZEB1 and ZEB2 without 3'UTR abrogated miR-101-induced EMT alteration, respectively. Our findings showed that miR-101 represents a redundant mechanism for the miR-200 family that regulates EMT through two major E-cadherin transcriptional repressors.

76 citations

Journal ArticleDOI
TL;DR: It is found that integrating mRNA and microRNA data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer, consisting of 8 major miRNAs and 214 mRNAs.
Abstract: Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition (EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas (TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This “paradox” can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating mRNA and microRNA (miRNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major miRNAs and 214 mRNAs. Among the 8 miRNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 miRNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer.

27 citations

Journal ArticleDOI
TL;DR: In this article , the authors studied the patterns of lymph node metastasis (LNM) of endometrial cancer and clarified the individualized clinical target volume delineations of regional lymph nodes (CTVn).
Abstract: Purpose: To study the patterns of lymph node metastasis (LNM) of endometrial cancer (EC) and to clarify the individualized clinical target volume delineations of regional lymph nodes (CTVn). Methods: Data from a total of 556 patients with EC who had undergone total hysterectomy associated with bilateral salpingo-oophorectomy (TH/BSO) and systematic lymphadenectomy were retrospectively examined. The clinicopathological factors related to LNM were analyzed using logistic regression analysis. Results: LNM was found in 76 of 556 patients, resulting in a metastasis rate of 13.67%. The rates of LNM in patients with fundus and cornua lesions were 7.56% for para-aortic nodes and 14.41% for pelvic lymph nodes. The rates of LNM in patients with sidewall lesions were 3.15% for para-aortic nodes and 10.22% for pelvic lymph nodes. The rates of LNM in patients with lower uterine segment and cervix lesions were 12.50% for para-aortic nodes and 26.67% for pelvic lymph nodes. Deep myometrial invasion, histological type, histological differentiation, and lymphovascular space invasion (LVSI) emerged as statistically significant risk factors for pelvic LNM of EC (P = 0.008, 0.015, < 0.001, 0.005, respectively). Grade 3 differentiation had a strong influence on LNM to the para-aortic nodes (P = 0.015). Conclusions: Myometrial invasion, histological type, histological differentiation, and LVSI were related to pelvic LNM and grade 3 was associated with para-aortic LNM. These factors should be considered comprehensively to design the CTVn for intensity-modulated radiation therapy (IMRT) of EC. For patients with lower uterine segment/cervix and fundus/cornua lesions, delineating the irradiation field of the para-aortic nodal region may confer a benefit.

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Journal ArticleDOI
24 Mar 2016-Oncogene
TL;DR: The results provide novel insights into the function of lncRNA-driven hepatocarcinogenesis, highlight the important role of ZEB1-AS1 and Z EB1 in HCC progression, and indicate that ZEB- AS1 may be served as a valuable prognostic biomarker for HCC.
Abstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Despite progress in diagnostics and treatment of HCC, its prognosis remains poor. Emerging studies showed that long noncoding RNAs (lncRNAs) have crucial regulatory roles in cancer biology. In the current study, differentially expressed lncRNAs between HCC and paired non-tumor tissues were identified using microarrays. The effects of a specific differentially expressed lncRNA (termed ZEB1-AS1) on tumor progression were investigated in vitro and in vivo. We found that ZEB1-AS1 is frequently upregulated in HCC samples, especially in metastatic tumor tissues. DNA methylation analysis shows a tumor-specific ZEB1-AS1 promoter hypomethylation. Aberrant methylation is tightly correlated with overexpression of ZEB1-AS1 in HCC. Patients with ZEB1-AS1 hypomethylation or with high ZEB1-AS1 expression have poor recurrence-free survival. Functionally, ZEB1-AS1 promotes tumor growth and metastasis, acts as an oncogene in HCC. The ZEB1-AS1 gene is located in physical contiguity with ZEB1 and positively regulates the ZEB1 expression. ZEB1 inhibition partially abrogates ZEB1-AS1-induced epithelial to mesenchymal transition (EMT) and cancer metastasis. Our results provide novel insights into the function of lncRNA-driven hepatocarcinogenesis, highlight the important role of ZEB1-AS1 and ZEB1 in HCC progression, and indicate that ZEB1-AS1 may be served as a valuable prognostic biomarker for HCC.

256 citations

Journal ArticleDOI
TL;DR: A role for the PTAR-miR-101-ZEB1 axis in OvCa is highlighted, which offers novel strategies for the prevention of metastasis in Ov Ca.
Abstract: Ovarian cancer (OvCa) is one of the most common malignant diseases of the female reproductive system in the world. The majority of OvCa is diagnosed with metastasis in the abdominal cavity. Epithelial-to-mesenchymal transition (EMT) plays a key role in tumor cell metastasis. However, it is still unclear whether long non-coding RNA (lncRNA) is implicated in EMT and influences cell invasion and metastasis in OvCa. In this study, using bioinformatcis analysis, we constructed a lncRNA-mediated competing endogenous RNA (ceRNA) network for mesenchymal OvCa and identified lncRNA AP000695.4, which we named pro-transition associated RNA (PTAR). PTAR was significantly up-regulated in the mesenchymal subtype samples compared with the epithelial subtype samples from the TCGA OvCa data sets. In addition, our study showed that PTAR expression was positively correlated with the expression level of ZEB1 in the mesenchymal OvCa samples. Meanwhile, we found that silencing miR-101 promoted cell migration, whereas the overexpression of miR-101 suppressed EMT and cell migration in OvCa cell lines through the regulation of ZEB1. Further analysis showed that enhanced expression of PTAR promoted EMT and metastasis through the regulation of miR-101, whereas silencing PTAR led to the attenuation of TGF-β1-induced tumorigenicity in ovarian cancer cells. Mechanistically, we found that PTAR acted as a ceRNA of miR-101, as forced expression of PTAR reduced the expression and activity of miR-101. More importantly, the knockdown of PTAR reduced tumorigenicity and metastasis in vivo. Taken together, the results from our study highlight a role for the PTAR-miR-101-ZEB1 axis in OvCa, which offers novel strategies for the prevention of metastasis in OvCa.

239 citations

Journal ArticleDOI
TL;DR: A review aims to describe these putative miRNAs in altering the WNT/β-catenin signalling in EMT, and whether targeting them is a useful therapeutic option for human invasive tumours.

200 citations

Journal ArticleDOI
TL;DR: Evidence is provided that enforced expression of CCAT1 exerts potent tumorigenic effects by promoting cell proliferation, invasion and migration and that it may serve as a prognostic cancer biomarker.
Abstract: Long non-coding RNAs (lncRNAs) are a group greater than 200 nucleotides in length. An increasing number of studies has shown that lncRNAs play important roles in diverse cellular processes, including proliferation, differentiation, apoptosis, invasion and chromatin remodelling. In this regard, deregulation of lncRNAs has been documented in human cancers. TUG1 is a recently identified oncogenic lncRNA whose aberrant upregulation has been detected in different types of cancer, including B-cell malignancies, oesophageal squamous cell carcinoma, bladder cancer, hepatocellular carcinoma and osteosarcoma. In these malignancies, knock-down of TUG1 has been shown to suppress cell proliferation, invasion and/or colony formation. Interestingly, TUG1 has been found to be downregulated in non-small cell lung carcinoma, indicative of its tissue-specific function in tumourigenesis. Pertinent to clinical practice, TUG1 may act as a prognostic biomarker for tumours. In this review, we summarize current knowledge concerning the role of TUG1 in tumour progression and discuss mechanisms associated with it.

186 citations

Journal ArticleDOI
TL;DR: An overview of the Notch signal in NSCLC is provided: its biological significance and therapeutic application, which shows promising effect in some cancer patients received treatment with Notch1 inhibitor.
Abstract: Through epithelial-mesenchymal transition (EMT), cancer cells acquire enhanced ability of migration and invasion, stem cell like characteristics and therapeutic resistance. Notch signaling regulates cell-cell connection, cell polarity and motility during organ development. Recent studies demonstrate that Notch signaling plays an important role in lung cancer initiation and cross-talks with several transcriptional factors to enhance EMT, contributing to the progression of non-small cell lung cancer (NSCLC). Correspondingly, blocking of Notch signaling inhibits NSCLC migration and tumor growth by reversing EMT. Clinical trials have showed promising effect in some cancer patients received treatment with Notch1 inhibitor. This review attempts to provide an overview of the Notch signal in NSCLC: its biological significance and therapeutic application.

184 citations