Dataset Information

Multidrug-Resistance Related Long Non-Coding RNA Expression Profile Analysis of Gastric Cancer.

ABSTRACT: The effect of chemotherapy of gastric cancer (GC) remains very poor because of multidrug resistance (MDR). However, the mechanisms underlying MDR of GC remains far from fully understood. The aim of this study is to illustrate the potential mechanisms of the MDR of GC at mainly the long non-coding RNA (lncRNA) level. In this study, GC cell line, SGC7901, and two MDR sublines, SGC7901/VCR and SGC7901/ADR were subjected to an lncRNA microarray analysis. Bioinformatics and verification experiments were performed to investigate the potential lncRNAs involved in the development of MDR. Pathway analysis indicated that 15 pathways corresponded to down-regulated transcripts and that 20 pathways corresponded to up-regulated transcripts (p-value cut-off is 0.05). GO analysis showed that the highest enriched GOs targeted by up-regulated transcripts were "system development" and the highest esenriched GOs targeted by the down-regulated transcripts were "sterol biosynthetic process". Our study is the first to interrogate differentially expressed lncRNAs in human GC cell line and MDR sublines and indicates that lncRNAs are worthwhile for further study to be the novel candidate biomarkers for the clinical diagnosis of MDR and potential targets for further therapy.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4546299 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Multidrug-Resistance Related Long Non-Coding RNA Expression Profile Analysis of Gastric Cancer.

Wang Ying Y Wu Kaichun K Yang Zhiping Z Zhao Qingchuan Q Fan Dongmei D Xu Po P Nie Yongzhan Y Fan Daiming D

PloS one 20150820 8

The effect of chemotherapy of gastric cancer (GC) remains very poor because of multidrug resistance (MDR). However, the mechanisms underlying MDR of GC remains far from fully understood. The aim of this study is to illustrate the potential mechanisms of the MDR of GC at mainly the long non-coding RNA (lncRNA) level. In this study, GC cell line, SGC7901, and two MDR sublines, SGC7901/VCR and SGC7901/ADR were subjected to an lncRNA microarray analysis. Bioinformatics and verification experiments w ...[more]

PMID: 26291830

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Project description:BackgroundLong non-coding RNAs (lncRNAs) are prevalently transcribed in the genome yet their potential roles in human cancers are not well understood. The aim of the present study was to determine the lncRNA expression profile in gastric cancer and its potential clinical value.MethodsThe global lncRNA expression profile in gastric cancer was measured by lncRNA microarray. Levels of two representative lncRNAs, H19 and uc001lsz, were confirmed by real-time reverse transcriptase-polymerase chain reaction. The relationship between their levels and clinicopathological factors of patients with gastric cancer was explored. A receiver operating characteristic (ROC) curve was constructed for differentiating gastric cancer from benign gastric diseases.ResultsTotal of 135 lncRNAs, which differential expression levels between tumor and non-tumorous tissues were more than twofold, were found (GEO No. GSE47850). The most down-regulated lncRNAs in gastric cancer tissues were FER1L4, uc001lsz, BG491697, AF131784, uc009ycs, BG981369, AF147447, HMlincRNA1600, and AK054588; while the most up-regulated ones were H19, HMlincRNA717, BM709340, BQ213083, AK054978, and DB077273. H19 was found highly expressed in stomach and liver cancer cell lines, while lowly expressed in lung cancer and prostate cancer cell lines. Uc001lsz was lowly expressed in gastric, lung and liver cancer cell lines, while highly expressed in prostate cancer. The areas under ROC curves were up to 0.613, 0.751, and 0.761 for H19, uc001lsz, and the combination, respectively.ConclusionsThe lncRNA expression profile in gastric cancer suggests the potential roles of lncRNAs in gastric cancer occurrence and development. The overexpression of H19 in gastric cancer suggests that H19 may be participated in gastric cancer. The reduced expression of uc001lsz in gastric cancer cell lines and tissues, its associations with TNM stage, and its dysregulation in early cancer and precancerous lesions suggest that uc001lsz may be a potential marker for the diagnosis of early gastric cancer.

Project description:Cisplatin-based chemotherapy is the standard treatment for non-small cell lung cancer (NSCLC). However, drug resistance emergences after treatment. Long non-coding RNA microvascular invasion in hepatic cancer (MVIH) plays an important role in drug resistance in a variety of cancers. This study investigates the role of nedaplatin on multidrug resistance in NSCLC and its relationship with MVIH. Lung cancer A549 and H1650 cells were treated with cisplatin to obtain multidrug-resistant A549/DDP and H1650/ DDP cells. A549/DDP and H1650/ DDP cells were treated with nedaplatin, MVIH siRNA and siRNA NC. It was found that both MVIH siRNA and nedaplatin significantly reduce the mRNA expression of MVIH in A549/DDP and H1650/ DDP cells. MTT assay showed that the proliferation of MDR cells was significantly higher than that of other cells. Nedaplatin and MVIH siRNA significantly inhibit the proliferation of A549 and H1650 cells. The results of colony formation assay were consistence with MTT results. Nedaplatin and MVIH siRNA significantly reduced colony formation in MDR cells. Flow cytometry showed that NDP and MVIH siRNA significantly decrease the proportion of cells in G0/G1 and increase the proportion of cells in S phase compared with untreated and MDR cells. The apoptotic rate of MDR cells was significantly lower than that of other cells, while the apoptosis rate of cells in NDP and MVIH siRNA group was significantly higher than that of the other three groups of cells. Wound healing assay and Transwell chamber experiments confirmed that both NDP and MVIH siRNA significantly reduced the migration and invasion abilities of MDR cells. The expression of E-cadherin in MDR cells was significantly lower than that in untreated cells, and the expression of N-cad, ?-SMA and Vimentin significantly increased in the MDR cells. NPD and MVIH siRNA reverse the EMT process. In conclusion, LncRNA MVIH is upregulated in drug resistant NSCLC cells. Nedaplatin can reduce the expression of MVIH and reverse EMT process, thus reversing the drug resistance of cisplatin in non-small cell lung cancer cells.

Project description:BackgroundHeterogeneity in colorectal cancer (CRC) patients provides novel strategies in clinical decision-making. Identifying distinctive subgroups in patients can improve the screening of CRC and reduce the cost of tests. Metabolism-related long non-coding RNA (lncRNA) can help detection of tumorigenesis and development for CRC patients.MethodsRNA sequencing and clinical data of CRC patients which extracted and integrated from public databases including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were set as training cohort and validation cohort. Metabolism-related genes were acquired from Kyoto Encyclopedia of Genes and Genomes (KEGG) and the metabolism-related lncRNAs were filtered using correlation analysis. The risk score was calculated based on lncRNAs with prognostic value and verified through survival curve, receiver operating characteristic (ROC) curve and risk curve. Prognostic factors of CRC patients were also analyzed. Nomogram was constructed based on the results of cox regression analyses. The different immune status was observed in the single sample Gene Set Enrichment Analysis (ssGSEA).ResultsThe training cohort and the validation cohort enrolled 432 and 547 CRC patients respectively. A total of 23 metabolism-related lncRNAs with prognostic value were screened out and 10 of which were significantly differentially expressed between tumour and normal tissues. Finally, 8 lncRNAs were used to establish a risk score (DICER1-AS1, PCAT6, GAS5, PRR7-AS1, MCM3AP-AS1, GAS6-AS1, LINC01082 and ADIRF-AS1). Patients were divided into high-risk and low-risk groups according to the median of risk scores in training cohort and the survival curves indicated that the survival prognosis was significantly different. The area under curve (AUC) of the ROC curve in two cohorts were both greater than 0.6. The age, tumour stage and risk score were selected as independent factors and used to construct a nomogram to predict CRC patients' survival rate with the c-index of 0.806. The ssGSEA indicated that the risk score was associated with immune cells and functions.ConclusionsOur systematic study established a metabolism-related lncRNA signature to predict outcomes of CRC patients which may contribute to individual prevention and treatment.

Dataset Information

Multidrug-Resistance Related Long Non-Coding RNA Expression Profile Analysis of Gastric Cancer.

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Multidrug-Resistance Related Long Non-Coding RNA Expression Profile Analysis of Gastric Cancer.

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