scholarly journals HOTAIR, HOXC13, and HOXC10 Are Overexpressed in Gastric Cancer

Author(s):  
Mahvash Habibi ◽  
Reza Fakhari ◽  
Mina Zamani ◽  
Hamid Galehdari

Abstract Gastric cancer is concerned as the second leading cause of tumor-associated death worldwide after lung tumors and is specified as one of the most common malignant cancers. Given the increasing importance of HOX genes in gastric cancer research, this study was aimed at exploring the expression profile of HOTAIR, HOXC13, HOXC10, HOXC13-AS, and HOXC‑AS3 in gastric cancer. To achieve this goal, 30 pairs of tumor and normal margin samples were assessed for these genes expression analyses via qRT-PCR. result we found that, the HOTAIR, HOXC13, and HOXC10 expression was significantly increased in cancer tissue samples in comparison with adjacent normal tissue samples, P<0.01. Moreover, there were significant positive correlations between the expressions of genes studied: HOXC‑AS3 and HOXC10 (r=0.52, P<0.003), HOXC13-AS and HOXC13 (r=0.57, P<0.001), HOTAIR and HOXC‑AS3 (r=0.39, P<0.03), HOTAIR and HOXC13-AS (r=0.36, P<0.05). The HOXC13 and HOXC10 expression exhibited a significant relationship with both distant metastasis and perineural invasion (metastasis: P<0.014, r=0.443 and P<0.0041, r=0.51 perineural invasion: P<0.025, r=0.41 and P<0.0017, r=0.55). The HOXC13-AS displayed a significant relationship with the sex factor so that in females the expression of this gene was higher than males (P<0.030, r=0.4). Our findings suggest that the expression of HOXC genes and HOTAIR lncRNA increased through gastric tumor progression and thus they possibly participate in malignant transformation and gastric carcinoma metastasis.

2014 ◽  
pp. 15-20
Author(s):  
Van Huy Tran ◽  
Thi Minh Thi Ha ◽  
Trung Nghia Van ◽  
Viet Nhan Nguyen ◽  
Phan Tuong Quynh Le ◽  
...  

Background: HER-2/neu is a predictive biomarker for treatment of gastric cancer using trastuzumab in combination with chemotherapy. This study aimed to evaluate the status of HER-2/neu gene amplification using fluorescence in situ hybridization (FISH) in gastric cancer. Patients and methods: thirty six gastric cancer patients were assessed HER-2/neu gene amplification by FISH using PathVysionTM HER-2 DNA Probe kit (including HER-2/neu probe and CEP-17 probe) with biopsy and surgical specimens. Results: The HER-2/neu gene amplification was observed in three cases (8.3%), the HER-2/neu gene amplification rate in Lauren’s intestinal-type and diffuse-type were 11.8% and 5.2%, respectively. Conclusion: We applied successfully FISH technique with gastric cancer tissue samples. This technique could be performed as routine test in gastric cancer in order to select patients that benefit from trastuzumab in combination with chemotherapy.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22079-e22079
Author(s):  
H. Benjamin ◽  
D. Lebanony ◽  
S. Tabak ◽  
N. Barabash ◽  
H. Gibori ◽  
...  

e22079 Background: Malignant mesothelioma is an aggressive pleural neoplasm, strongly linked to environmental exposures such as asbestos. Mesothelioma can be difficult to differentiate from other tumors in the lung or pleura such as primary lung adenocarcinoma presenting with pleural effusion or metastatic adenocarcinoma from extrathoracic sites. We addressed the increasing need for accurate differential diagnosis of these tumors by developing a diagnostic assay based on expression levels of microRNAs, a family of small, non-coding RNAs whose tissue-specificity has proven applicability for identification of cancer tissue type and histology. Methods: We developed protocols for extraction of high-quality RNA that retain the microRNA fraction from FFPE tissue samples. Microarrays were used for initial profiling. qRT-PCR was used to validate results and to develop a diagnostic assay. Results: We identified microRNAs that are differentially expressed between mesothelioma, lung adenocarcinoma, and other confounding tumor types. A diagnostic assay (miRview™ meso) was developed, that utilizes qRT-PCR measurement of a small set of microRNAs to differentiate between mesothelioma and non-mesothelioma samples. After establishing this profile in more than 30 mesotheliomas and 200 samples of confounding tumors, the microRNA biomarkers were measured using a standardized protocol on a blinded test set. The assay had accuracy greater than 90% in differentiating mesothelioma from other confounding tumor types. More than ¾ of samples were classified with high confidence, and these samples were all correctly identified. Conclusions: MicroRNAs are emerging as effective cancer biomarkers. A robust and simple assay based on the expression level of a few microRNA biomarkers can accurately differentiate mesothelioma from other possible tumors in the lung and pleura. This assay provides an important new tool for diagnosing mesothelioma. [Table: see text]


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Chuanhui Sun ◽  
Changsong Han ◽  
Peng Wang ◽  
Yinji Jin ◽  
Yanan Sun ◽  
...  

The purpose of this study was to investigate the HOX gene expression profile in laryngeal squamous cell carcinoma (LSCC) and assess whether some genes are associated with the clinicopathological features and prognosis in LSCC patients. The HOX gene levels were tested by microarray and validated by qRT-PCR in paired cancerous and adjacent noncancerous LSCC tissue samples. The microarray testing data of 39 HOX genes revealed 15 HOX genes that were at least 2-fold upregulated and 2 that were downregulated. After qRT-PCR evaluation, the three most upregulated genes (HOXB9, HOXB13, and HOXD13) were selected for tissue microarray (TMA) analysis. The correlations between the HOXB9, HOXB13, and HOXD13 expression levels and both clinicopathological features and prognosis were analyzed. Three HOX gene expression levels were markedly increased in LSCC tissues compared with adjacent noncancerous tissues (P<0.001). HOXB9 was found to correlate with histological grade (P<0.01) and prognosis (P<0.01) in LSCC. In conclusion, this study revealed that HOXB9, HOXB13, and HOXD13 were upregulated and may play important roles in LSCC. Moreover, HOXB9 may serve as a novel marker of poor prognosis and a potential therapeutic target in LSCC patients.


2019 ◽  
Author(s):  
Yue Pan ◽  
Weixing Chen ◽  
Xin Yuan ◽  
Hongpeng Lu ◽  
Lei Xu ◽  
...  

Abstract Background: Recent studies have shown that microRNA-99a(miR-99a)plays a key role in the development of virious malignancies; however, its relationship with gastric cancer remains unclear. In this study, we investigated the functions and potential mechanisms of miR-99a in gastric cancer. Methods: Real-time qRT-PCR was used to assess the expression levels of miR-99a in gastric cancer tissue samples and cell lines compared to their matched adjacent normal tissues and a normal gastric mucosa epithelial cell line, respectively. SGC-7901 cells were transfected with miR-99a mimics and negative controls to determine the effects of miR-99a overexpression on cell proliferation, cell cycle transition, migration and invasion of gastric cancer cells in vitro . The role of miR-99a in endogenous c-Src expression in gastric cancer cells was also investigated by qRT-PCR and Western blotting. Results: Our results showed a significant increase in miR-99a expression in both gastric cancer tissues and cells compared to normal tissues and cells. Overexpression of miR-99a significantly promoted the cell proliferation, migration and invasion of gastric cancer cells compared to normal cells, with a concurrent increase in the S+G2 phases of the cell cycle. Further investigations found that miR-99a overexpression led to significant upregulation of endogenous c-Src. Conclusion: Taken together, our findings suggest that miR-99a may act as a tumour promoter in the pathogenesis of gastric cancer by indirectly modulating c-Src expression.


2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Jie Zhang ◽  
Wei-qing Qiu ◽  
Hongyi Zhu ◽  
Hua Liu ◽  
Jian-hua Sun ◽  
...  

Abstract Gastric cancer (GC) is one of the most leading malignancies. Long noncoding RNA is related to GC. In this study, 11 miRNAs in the exosomes and six lncRNAs in the tissues was examined by qRT-PCR. Correlation analysis was used to analyze the relationship between miRNAs in exosome and lncRNAs in the tissues. Four miRNAs level in GC tissues were examined by qRT-PCR. MTT was used to determine cell viability. Flow cytometry was used to quantify the apoptotic cells. Transwell assay was used to examine the migration and invasion capacity. Dual-luciferase assay was used to examine the interaction between HOTAIR and miR-30a or -b. Capillary formation was used to determine the capillary formation capacity. Weak negative correlations were found between HOTAIR and miR-30a or -b in GC tissue samples. Interestingly, strong negative correlations were identified between the HOTAIR level in GC tissue samples and the miR-30a or -b levels in plasma exosomes. HOTAIR knockdown GC cells exhibited decreased migration, invasion, proliferation, and upregulated apoptosis, which released more miR-30a and -b into the exosomes. KRAS was upregulated when co-cultured with exosomes from HOTAIR overexpressed cells, and promoted GC cells proliferation, migration, and invasion. Meanwhile, HUVEC cells expressed increased VEGF-A and formatted more capillaries. Subsequently, we identified a 10mer target site of miR-30a or -b in HOTAIR sequence, and the overexpression of HOTAIR induced the degradation of miR-30a or -b, indicating a ceRNA role of HOTAIR. We report the negative correlation between the plasma miRNAs level and GC tissue HOTAIR expression for the first time and unveiled the ceRNA role of HOTAIR in GC. HOTAIR functions as an onco-lncRNA regulating the level of miR-30a and -b in both GC cells and exosomes. These findings may give insight into understanding the mechanism of GC pathogenesis and provide new biomarkers for clinical diagnosis.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 34-34
Author(s):  
Zheng Chen ◽  
Shoumin Zhu ◽  
Jun Hong ◽  
Abbes Belkhiri ◽  
Wael El-Rifai

34 Background: Gastric cancer is the second most frequent cause of cancer-related death worldwide. We have previously shown that Dopamine and cAMP regulated phosphoprotein MW 32 kDa (DARPP-32) and its truncated form (t-DARPP) are overexpressed in two-thirds of gastric adenocarcinomas. Angiopoietin 2 (ANGPT2) -TIE2 signaling is a secreted protein that acts as a key regulator of adult vascular homeostasis and blood vessel formation. Methods: The expression of DARPP-32 in the multi-step carcinogenesis cascade was examined using IHC analysis on 533 samples. ANGPT2 mRNA level was detected by real-time quantitative polymerase chain reaction (PCR) in 30 gastric cancer tissue samples and 30 normal gastric tissues. DARPP-32 and t-DARPP were over expressed using stable and transient expression in AGS and MKN-28 gastric cancer cell lines, lacking endogenous DARPP-32 to investigate the induction of ANGPT2 by DARPP-32 and t-DARPP. Results: We found that ANGPT2 was higher expressed in cancer samples than normal tissues from RT-PCR. We also found gastric cancer tissue samples expressed higher DARPP-32 and t-DARPP mRNA than normal gastric tissues. Over expression of DARPP-32 and t-DARPP led to a significant increase of the mRNA and protein levels of ANGPT2 as compared to empty vector control. Consistent with these findings, the condition media from DARPP-32 and t-DARRP expressing cells showed high levels of secreted ANGPT-2. TNF-α treatment induced the levels of ANGPT2 further in DARPP-32 and t-DARPP expressing cells as compared to control. Of note, this increase in NF-κB activity was significantly higher in DARPP-32 and t-DARPP expressing cells as compared to control. To confirm the angiogenic potential, we used condition media from DARPP-32 and t-DARPP expressing AGS cells and demonstrated its ability to stimulate tube formation on human umbilical vein endothelial cells (HUVEC) models than the condition medium from control cells. Conclusions: Our results suggest that DARPP-32 and t-DARPP over expression may participate in the angiogenesis of gastric cancer. The in vitro studies indicate that DARPP-32 and t-DARPP play a role in up regulation of ANGPT2 in gastric cancer cells by enhancing the TNF-α induced activation of NF-κB signaling pathway.


2021 ◽  
Author(s):  
Chao Zhang ◽  
Shutao Zhao ◽  
Xudong Wang

Abstract Background: Abnormal glucose metabolism leading to tumor proliferation and metastasis is an important area of interest in cancer treatment. The purpose of this study was to investigate the effects of clinical expression of glucose metabolism-related genes Linc-00475 and p53 on glycolysis and survival.Methods: A key differential gene Linc-00475 was screened using a metabolic database, and its downstream gene, p53, was predicted. A total of 107 gastric cancer tissue samples from patients diagnosed at our center between 2011 and 2013 were selected. The expression levels of Linc-00475 and p53 were detected via in situ hybridization or immunohistochemistry. Chi-square test was used to analyze the relationship between Linc-00475 and p53 expression and clinicopathological factors. Kaplan-Meier method and log rank test were used to analyze patients’ overall survival. To determine the effect of Linc-00475 on glycolysis, qRT-PCR and western blot were utilized to evaluate the regulatory relationship between Linc-00475 and p53.Results: High expression of Linc-00475 (P < 0.001) and low expression of p53 (P < 0.01) were associated with poor prognosis. There was a negative correlation between the expression of Linc-00475 and p53 in gastric cancer (Pearson's coefficient test, r = -0.405; P < 0.001). The co-expression of high-level Linc-00475 and low-level p53 can thus be used as an independent prognostic factor (P = 0.001). Linc-00475 was also shown to regulate aerobic glycolysis. Western blot and qRT-PCR demonstrated that Linc-00475 regulates the expression of p53.Conclusion: The co-expression of Linc-00475 and p53 can be used as a reference index for evaluating the prognosis of gastric cancer. Linc-00475 regulates p53, thereby affecting glycolysis.


2020 ◽  
Author(s):  
Huijuan Shi ◽  
Kejun Li ◽  
Jinxin Feng ◽  
Gaojie Liu ◽  
Yanlin Feng ◽  
...  

Abstract Background: To explore the molecular mechanisms and modulatory effects of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the hyperthermia-induced gastric cancer cell death. Methods: Combined qRT-PCR and GLS activity detection of glutamine metabolism, we demonstrate the difference of expression of MALAT1 and miR-206 in normal or cancer tissue/ several cell lines and the roles of two in regulation of glutamine, respectively. The relation of MALAT1 and miR-206 was research by bioinformatical analysis and luciferase report. In addition, the molecular regulation between apoptotic effects and MALAT1-miR-206-GLS axis in gastric cancer after mild hyperthermia treatments were discovered by western blotting, luciferase report, quantitative real-time PCR (qRT-PCR), GLS activity detection of glutamine metabolism and cell viability test. Results: MALAT1 positively associated with GC by promoting glutamine metabolism under short time hyperthermia treatment, it involved in an adaptive reaction, an increased glutamine metabolism rate which could be further overridden by long time hyperthermia exposures. miR-206 could inhibit glutamine metabolism of GC and target 3’UTR of GLS which has oncogenic functions in GC directly. In addition, miR-206-suppresed glutamine metabolism was through direct targeting GLS. LncRNA MALAT1 inhibited miR-206 expression in GC by sponging it as a competing endogenous RNA. In summary, MALAT1-promoted glutamine metabolism was through the miR-206-GLS axis. Furthermore, we demonstrated effective approaches from the MALAT1-miR-206 axis for enhancing the mild hyperthermia-induced cancer death under a short time. Conclusions: Taken together, the MALAT1-miR-206-glutamine metabolism axis is a new strategy for enhancing the selectivity of hyperthermia treatments specific to GC cells


2020 ◽  
Author(s):  
Xiao-Qing Lu ◽  
Jia-qian Zhang ◽  
Jun Qiao ◽  
Sheng-Xiao Zhang ◽  
Meng-Ting Qiu ◽  
...  

Abstract Background: Gastric cancer (GC) is one of the most common solid malignant tumors worldwide with a high-recurrence-rate. Identifying the molecular signatures and specific biomarkers of GC might provide novel clues for GC prognosis and targeted therapy.Methods: Gene expression profiles were obtained from the ArrayExpress and Gene Expression Omnibus database. Differentially expressed genes (DEGs) were picked out by R software. The hub genes were screened by cytoHubba plugin. Their prognostic values were assessed by Kaplan–Meier survival analyses and the gene expression profiling interactive analysis (GEPIA). Finally, qRT-PCR in GC tissue samples was established to validate these DEGs. Results: Total of 295 DEGs were identified between GC and their corresponding normal adjacent tissue samples in E-MTAB-1440, GSE79973, GSE19826, GSE13911, GSE27342, GSE33335 and GSE56807 datasets, including 117 up-regulated and 178 down-regulated genes. Among them, 7 vital upregulated genes (HMMR, SPP1, FN1, CCNB1, CXCL8, MAD2L1 and CCNA2) were selected. Most of them had a significantly worse prognosis except SPP1. Using qRT-PCR, we validated that their transcriptions in our GC tumor tissue were upregulated except SPP1 and FN1, which correlated with tumor relapse and predicts poorer prognosis in GC patients.Discussion: We have identified 5 upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) in GC patients with poor prognosis using integrated bioinformatical methods, which could be potential biomarkers and therapeutic targets for GC treatment.


2014 ◽  
Vol 23 (3) ◽  
pp. 249-253 ◽  
Author(s):  
Dor Mohammad Kordi-Tamandani ◽  
Shahrbbanou Karimi Davani ◽  
Taybeh Baranzehi ◽  
Simin Hemati

AbstractBackground & Aim: Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) is a crucial immune-checkpoint receptor regulating T-cell activation. The current study was carried out to evaluate the function of CTLA4 gene in patients with gastric cancer.Methods: The methylation of CTLA4 gene promoter was evaluated by methylation-specific polymerase chain reaction (MSP) technique using 85 paraffin-embedded gastric cancer tissue samples and normal tissue on the tumor margins as control tissue samples. Expression analysis was performed on paraffin-embedded tissue samples (25 each of cancerous and normal tissues) using Real-time PCR.Results: Statistically significant differences were observed between the tumor and margin-cell areas withrespect to promoter methylation status (OR = 4.829, 95% CI: 2.46-9.48, p < 0.001) and CTLA4 expression profile (mean ± SD = 7.56 ± 17.35, p = 0.04).Conclusion: To the best of our knowledge, the current study is the first one highlighting the association between promoter hypermethylation of CTLA4 gene, decreased CTLA4 expression, and increased risk of gastric cancer.


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