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Genomic analysis of drug resistant pancreatic cancer cell line by combining long non-coding RNA and mRNA expression profling.

ABSTRACT: Recently, more and more studies show that long non-coding RNAs (lncRNAs) play a very important role in various biological processes. However, research on lncRNA in the tumor cell drug resistance of it is seldom reported. In this study, gemcitabine-resistant pancreatic cancer cell line SWl990/GZ was obtained by treating parental cell line SWl990 in vitro with increasing dosage of gemcitabine in culture medium intermittently for ten months. We identified 4983 of 13310 detected lncRNAs demonstrated > 2-fold abnormally expressed in response to the gemcitabine-resistant, among of them, 1993 and 2990 lncRNAs were upregulated and downregulated. Meanwhile, 4759 mRNAs exhibited at least a 2-fold, of these, 2671 and 2088 mRNAs were upregulated and downregulated. Gene Ontology analysis and Pathway analysis revealed that differential expression mRNA involved in significant biological regulatory function and some genes may be particular to pancreatic cancer chemotherapy resistance. Quantitative real time PCR confirmed the changes of six lncRNAs (RP11-58D2.1, lincRNA-ZNF532, AP000221.1, CTC-338M12.5, CR619813, DDX6P) and nine mRNAs (SYT1, FAM171B, ZNF331, FAM187B, CYP1A1, SRXN1, HIST1H2BL, TOMM40L and SPP1) in SW1990 and SW1990/GZ. We also found that the upregulating of gemcitabine on the expression of lincRNA-ZNF532 was time-dependent. Gemcitabine at a range from 1.0 ?M to 16.0 ?M induced a increase of lincRNA-ZNF532 in SW1990 cells. The relative level of DDX6P is opposite to that of lincRNA-ZNF53 in the same circumstance. In conclusion, the dysregulated lncRNAs and mRNAs identified in this work may represent good candidates for future diagnostic or prognostic biomarkers and therapeutic targets.

SUBMITTER: Zhou M

PROVIDER: S-EPMC4348861 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Genomic analysis of drug resistant pancreatic cancer cell line by combining long non-coding RNA and mRNA expression profling.

Zhou Ming M Ye Zhenyu Z Gu Yizhou Y Tian Bian B Wu Bian B Li Juncheng J

International journal of clinical and experimental pathology 20150101 1

Recently, more and more studies show that long non-coding RNAs (lncRNAs) play a very important role in various biological processes. However, research on lncRNA in the tumor cell drug resistance of it is seldom reported. In this study, gemcitabine-resistant pancreatic cancer cell line SWl990/GZ was obtained by treating parental cell line SWl990 in vitro with increasing dosage of gemcitabine in culture medium intermittently for ten months. We identified 4983 of 13310 detected lncRNAs demonstrated ...[more]

PMID: 25755691

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Project description:Background: Pancreatic cancer is a devastating disease with a low five-year survival rate. Dendritic cells (DCs), which are the most potent antigen-presenting cells in the human body, play a pivotal role in the immune response. However, few studies have investigated the role of pancreatic cancer-derived exosomes (PEXs) in DC-meditated immune escape. The expression profiles of long noncoding RNAs (lncRNAs) and mRNAs of PEX-treated dendritic cells are unknown. Methods: We used integrated lncRNA and mRNA microarrays to determine the expression profiles of PEX-treated DCs and normal DCs derived from five healthy donors. Gene Ontology (GO), KEGG, and cancer genomics analyses were performed to identify significant functions, pathways, and the associations of differentially expressed mRNAs. A coexpression network was constructed to identify the correlation between differentially expressed lncRNAs and mRNAs and further validated using real-time quantitative PCR in twenty healthy donors. The AnnoLnc program was used to perform an annotation analysis of lncRNAs. Results: We identified 3,227 and 924 differentially expressed lncRNAs and mRNAs, respectively, in PEX-treated DCs. GO and pathway analysis revealed differentially expressed mRNAs involved in many critical biological processes and molecular functions. Cancer genomics analysis revealed that 36 of the most differentially expressed mRNAs were involved in a pancreatic cancer network and were associated with many critical mutated genes such as TP53, KRAS, SMAD4, and CDKN2A. LncRNAs such as ENST00000560647 and mRNAs such as legumain (lgmn) were differentially expressed in PEX-treated DCs, and the data were validated using RT-qPCR. Conclusions: To our knowledge, this is the first study to detect the differential expression of lncRNAs and mRNAs associated with PEX-treated DCs. LncRNAs such as ENST00000560647 and mRNAs such as lgmn might play a critical role in immune escape of DCs treated with PEX. Further investigation is required to validate the functions and associations of these RNAs.

Project description:Long non-coding RNAs (lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury tissue from three patients of the 101st Hospital of the People's Liberation Army, China (specifically, a 36-year-old male, a 52-year-old female, and a 49-year-old female), who were diagnosed with traumatic brain injury and underwent brain contusion removal surgery. Tissue surrounding the brain contusion in the three patients was used as control tissue to observe expression characteristics of lncRNAs and mRNAs in human traumatic brain injury tissue. Volcano plot filtering identified 99 lncRNAs and 63 mRNAs differentially expressed in frontotemporal tissue of the two groups (P < 0.05, fold change > 1.2). Microarray analysis showed that 43 lncRNAs were up-regulated and 56 lncRNAs were down-regulated. Meanwhile, 59 mRNAs were up-regulated and 4 mRNAs were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed 27 signaling pathways associated with target genes and, in particular, legionellosis and influenza A signaling pathways. Subsequently, a lncRNA-gene network was generated, which showed an absolute correlation coefficient value > 0.99 for 12 lncRNA-mRNA pairs. Finally, quantitative real-time polymerase chain reaction confirmed different expression of the five most up-regulated mRNAs within the two groups, which was consistent with the microarray results. In summary, our results show that expression profiles of mRNAs and lncRNAs are significantly different between human traumatic brain injury tissue and surrounding tissue, providing novel insight regarding lncRNAs' involvement in human traumatic brain injury. All participants provided informed consent. This research was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-TCC-13004002) and the protocol version number is 1.0.

Dataset Information

Genomic analysis of drug resistant pancreatic cancer cell line by combining long non-coding RNA and mRNA expression profling.

Publications

Genomic analysis of drug resistant pancreatic cancer cell line by combining long non-coding RNA and mRNA expression profling.

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