Adenoviral Delivery of the EMX2 Gene Suppresses Growth in Human Gastric Cancer

Li, Jie; Mo, Minli; Zhao, Chen; Chen, Zhe; Sheng, Qing; Mu, Hang; Zhang, Fang; Zhi, Xiao; He, Biao; Zhou, Hai‐Meng

doi:10.1371/journal.pone.0045970

Cited by 20 publications

(29 citation statements)

References 42 publications

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“…More recently, loss of EMX2 expression has been demonstrated in gastric cancer cell lines and primary gastric cancer. EMX2 down-regulation was associated with promoter hypermethylation and the adenoviral delivery of EMX2 in a mouse model of gastric cancer significantly suppressed tumor growth [ 16 ]. Thus, these previous observations support our present finding that down-regulation of EMX2 has protumorigenic effects in colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

EMX2 gene expression predicts liver metastasis and survival in colorectal cancer

et al. 2017

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BackgroundThe Empty Spiracles Homeobox (EMX-) 2 gene has been associated with regulation of growth and differentiation in neuronal development. While recent studies provide evidence that EMX2 regulates tumorigenesis of various solid tumors, its role in colorectal cancer remains unknown. We aimed to assess the prognostic significance of EMX2 expression in stage III colorectal adenocarcinoma.MethodsExpression levels of EMX2 in human colorectal cancer and adjacent mucosa were assessed by qRT-PCR technology, and results were correlated with clinical and survival data. siRNA-mediated knockdown and adenoviral delivery-mediated overexpression of EMX2 were performed in order to investigate its effects on the migration of colorectal cancer cells in vitro.ResultsCompared to corresponding healthy mucosa, colorectal tumor samples had decreased EMX2 expression levels. Furthermore, EMX2 down-regulation in colorectal cancer tissue was associated with distant metastasis (M1) and impaired overall patient survival. In vitro knockdown of EMX2 resulted in increased tumor cell migration. Conversely, overexpression of EMX2 led to an inhibition of tumor cell migration.ConclusionsEMX2 is frequently down-regulated in human colorectal cancer, and down-regulation of EMX2 is a prognostic marker for disease-free and overall survival. EMX2 might thus represent a promising therapeutic target in colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

EMX2 gene expression predicts liver metastasis and survival in colorectal cancer

et al. 2017

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“…However, fundamental questions still need to be fully addressed, such as the molecular mechanisms that drive the aberrant expression, downstream targets and signaling pathways that promote oncogenesis. To investigate the role that homeobox genes play in oncogenesis, our group and collaborators have recently identified EMX2 as being epigenetically down-regulated and serving as a putative novel tumor suppressor in lung adenocarcinomas and gastric cancer [ 16 – 18 ]. In the present study, we investigated whether EMX2 was also down-regulated and what role it might play in human lung SCC.…”

Section: Discussionmentioning

confidence: 99%

“…The homeobox gene family encodes transcription factors, regulating morphogenesis and cell differentiation during embryogenesis by activating or repressing the expression of target genes [ 12 ]. In addition to its important role in embryologic development, several studies suggest that EMX2 may be involved in human tumorigenesis [ 13 – 16 ]. More recently, we have demonstrated epigenetic silencing of EMX2 expression in lung adenocarcinomas and its association with poor clinical outcomes in early stage lung adenocarcinoma patients [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas

Yue

Che

et al. 2015

PLoS ONE

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BackgroundSquamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer (NSCLC). Current staging methods do not adequately predict outcome for this disease. EMX2 is a homeo-domain containing transcription factor known to regulate a key developmental pathway. This study assessed the significance of EMX2 as a prognostic and predictive marker for resectable lung SCC.MethodsTwo independent cohorts of patients with lung SCC undergoing surgical resection were studied. EMX2 protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. EMX2 expression levels in tissue specimens were scored and correlated with patient outcomes. Chemo-sensitivity of lung SCC cell lines stably transfected with EMX2 shRNAs to cisplatin, carboplatin, and docetaxel was examined in vitro.ResultsEMX2 expression was down-regulated in lung SCC tissue samples compared to their matched adjacent normal tissues. Positive EMX2 expression was significantly associated with improved overall survival in stage I lung SCC patients, and in stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. EMX2 expression was also associated with expression of EMT markers in both lung SCC cell lines and tissue samples. Knock-down of EMX2 expression in lung SCC cells promoted chemo-resistance and cell migration.ConclusionsEMX2 expression is down-regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT). EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy.

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“…Moloney murine leukemia virus (M-MLV) reverse tanscriptase, hygromycin B and Hoechst 33342 were obtained from Invitrogen. The gastric tumor tissues were kindly gifted by Professor Zhou HM (Tsinghua University) and the description of the tissues has been described elsewhere [35]. Actinomycin D, agarose, ribonuclease A (RNase A), propidium iodide, H 2 O 2 , hydroxyl urea (HU), cisplatin, Triton X-100, bovine serum albumin (BSA), NaCl and mouse anti-β-actin antibody were purchased from Sigma.…”

Section: Methodsmentioning

confidence: 99%

“…To examine the expression status of PARN in human gastric cancer, semi-quantitative and real-time RT-PCR was used to examine the mRNA level of PARN in two human gastric cancer cell lines and six pairs of gastric tumor tissues from patients described elsewhere [35]. The results (Fig.…”

Section: Expression Level Of Parn In Human Gastric Cancer Cells and Tmentioning

confidence: 99%

Depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression

Zhang

Yan

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Regulation of mRNA decay plays a crucial role in the post-transcriptional control of cell growth, survival, differentiation, death and senescence. Deadenylation is a rate-limiting step in the silence and degradation of the bulk of highly regulated mRNAs. However, the physiological functions of various deadenylases have not been fully deciphered. In this research, we found that poly(A)-specific ribonuclease (PARN) was upregulated in gastric tumor tissues and gastric cancer cell lines MKN28 and AGS. The cellular function of PARN was investigated by stably knocking down the endogenous PARN in the MKN28 and AGS cells. Our results showed that PARN-depletion significantly inhibited the proliferation of the two types of gastric cancer cells and promoted cell death, but did not significantly affect cell motility and invasion. The depletion of PARN arrested the gastric cancer cells at the G0/G1 phase by upregulating the expression levels of p53 and p21 but not p27. The mRNA stability of p53 was unaffected by PARN-knockdown in both types of cells. A significant stabilizing effect of PARN-depletion on p21 mRNA was observed in the AGS cells but not in the MKN28 cells. We further showed that the p21 3'-UTR triggered the action of PARN in the AGS cells. The dissimilar observations between the MKN28 and AGS cells as well as various stress conditions suggested that the action of PARN strongly relied on protein expression profiles of the cells, which led to heterogeneity in the stability of PARN-targeted mRNAs.

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Adenoviral Delivery of the EMX2 Gene Suppresses Growth in Human Gastric Cancer

Cited by 20 publications

References 42 publications

EMX2 gene expression predicts liver metastasis and survival in colorectal cancer

EMX2 gene expression predicts liver metastasis and survival in colorectal cancer

EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas

Depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression

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