HOXD9 promotes epithelial–mesenchymal transition and cancer metastasis by ZEB1 regulation in hepatocellular carcinoma

Lv, Xiupeng; Li, Linlin; Lv, Li; Qu, Xiaotong; Shi, Jin; Li, Kejun; Deng, Xiaoqin; Cheng, Lei; He, Hui; Li, Dong

doi:10.1186/s13046-015-0245-3

Cited by 73 publications

(75 citation statements)

References 36 publications

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“…This family is highly conserved throughout the whole evolution process and is involved in many signal transduction pathways, such as cell development, migration and differentiation . HOXD9 is a member of the homeobox gene family . HOXD9 showed high upregulation in invasive HCC cells.…”

Section: Discussionmentioning

confidence: 99%

A four‐gene‐based prognostic model predicts overall survival in patients with hepatocellular carcinoma

Long

Zhang

Wan

et al. 2018

J Cellular Molecular Medi

128

123

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With the development of new advances in hepatocellular carcinoma (HCC) management and noninvasive radiological techniques, high‐risk patient groups such as those with hepatitis virus are closely monitored. HCC is increasingly diagnosed early, and treatment may be successful. In spite of this progress, most patients who undergo a hepatectomy will eventually relapse, and the outcomes of HCC patients remain unsatisfactory. In our study, we aimed to identify potential gene biomarkers based on RNA sequencing data to predict and improve HCC patient survival. The gene expression data and clinical information were acquired from The Cancer Genome Atlas (TCGA) database. A total of 339 differentially expressed genes (DEGs) were obtained between the HCC (n = 374) and normal tissues (n = 50). Four genes (CENPA, SPP1, MAGEB6 and HOXD9) were screened by univariate, Lasso and multivariate Cox regression analyses to develop the prognostic model. Further analysis revealed the independent prognostic capacity of the prognostic model in relation to other clinical characteristics. The receiver operating characteristic (ROC) curve analysis confirmed the good performance of the prognostic model. Then, the prognostic model and the expression levels of the four genes were validated using the Gene Expression Omnibus (GEO) dataset. A nomogram comprising the prognostic model to predict the overall survival was established, and internal validation in the TCGA cohort was performed. The predictive model and the nomogram will enable patients with HCC to be more accurately managed in trials testing new drugs and in clinical practice.

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Section: Discussionmentioning

confidence: 99%

A four‐gene‐based prognostic model predicts overall survival in patients with hepatocellular carcinoma

Long

Zhang

Wan

et al. 2018

J Cellular Molecular Medi

128

123

View full text Add to dashboard Cite

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“…Epithelial-mesenchymal transition (EMT), a morphogenetic process that results in a loss of epithelial characteristics and acquisition of a mesenchymal phenotype, has become one of the most exciting and increasingly investigated areas in cancer biology [30–32]. Emerging evidence suggests that EMT plays a key role in cancer progression [33–35].…”

Section: Discussionmentioning

confidence: 99%

LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway

et al. 2016

Oncotarget

231

210

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Highly upregulated in liver cancer (HULC), a lncRNA that is considered a key molecule in human liver cancer, has recently been revealed to be involved in hepatocellular carcinoma (HCC) development and progression [1, 2]. It has been reported that HULC can promote tumor invasion and metastasis of HCC, but its function and mechanism of action in HCC have not been elucidated. In this study, we found that HULC was aberrantly up-regulated in HCC tissues and associated with TNM stage, intrahepatic metastases, HCC recurrence, and postoperative survival. HULC depletion inhibited the growth and metastasis of HCC cell lines in vitro and in vivo. Moreover, HULC contributes to ZEB1-induced epithelial-mesenchymal transition (EMT), a requirement for tumor invasion and metastasis that plays a key role in cancer progression. This effect of ZEB1 was inhibited by HULC siRNA. We conclude that the HULC functioned as a competing endogenous RNA (ceRNA) to mediate EMT via up-regulating ZEB1. In this way, it sequesters the miR-200a-3p signaling pathway to facilitate HCC metastasis. HULC comes into play as an oncogene in HCC, acting mechanistically by inducing HCC cells to activate EMT. Such an effect promotes tumor progression and metastasis through the miR-200a-3p/ZEB1 signaling pathway. The identification of this novel pathway that links high expression levels of HULC with EMT in HCC cells may serve as the foundation for the development of novel anti-tumor therapeutics.

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“…In a validation cohort of 145 melanoma patients, HOXD9 hypermethylation in lymph node metastases was associated with shorter progression-free and overall survival [49]. The function of HOXD9 in melanoma is incompletely understood, but studies from HCC suggest that it significantly enhances migration, invasion, and metastasis [118]. Methylation and silencing of ESRP1 has been also associated with altered CD44v6 expression, which could predict brain metastasis-free survival [119].…”

Section: Differential Dna Methylation As a Biomarker In Melanomamentioning

confidence: 99%

Aberrant DNA methylation in melanoma: biomarker and therapeutic opportunities

2017

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Aberrant DNA methylation is an epigenetic hallmark of melanoma, known to play important roles in melanoma formation and progression. Recent advances in genome-wide methylation methods have provided the means to identify differentially methylated genes, methylation signatures, and potential biomarkers. However, despite considerable effort and advances in cataloging methylation changes in melanoma, many questions remain unanswered.The aim of this review is to summarize recent developments, emerging trends, and important unresolved questions in the field of aberrant DNA methylation in melanoma. In addition to reviewing recent developments, we carefully synthesize the findings in an effort to provide a framework for understanding the current state and direction of the field. To facilitate clarity, we divided the review into DNA methylation changes in melanoma, biomarker opportunities, and therapeutic developments. We hope this review contributes to accelerating the utilization of the diagnostic, prognostic, and therapeutic potential of DNA methylation for the benefit of melanoma patients.

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HOXD9 promotes epithelial–mesenchymal transition and cancer metastasis by ZEB1 regulation in hepatocellular carcinoma

Cited by 73 publications

References 36 publications

A four‐gene‐based prognostic model predicts overall survival in patients with hepatocellular carcinoma

A four‐gene‐based prognostic model predicts overall survival in patients with hepatocellular carcinoma

LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway

Aberrant DNA methylation in melanoma: biomarker and therapeutic opportunities

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