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Long noncoding RNAs: role and contribution in pancreatic cancer.

ABSTRACT: Noncoding RNAs are proclaimed to be expressed in various cancer types and one such type is found to be pancreatic ductal adenocarcinoma (PDAC). The long noncoding RNAs (LncRNAs) affect the migration, invasion, and growth of tumor cells by playing important roles in the process of epigenesis, post-transcription, and transcriptional regulation along with the maintenance of apoptosis and cell cycle. It is quite subtle whether the alterations in lncRNAs would impact PDAC progression and development. This review throws a spotlight on the lncRNAs associated with tumor functions: MALAT-1, HOTAIR, HOXA13, H19, LINC01559, LINC00460, SNHG14, SNHG16, DLX6-AS1, MSC-AS1, ABHD11-AS1, DUXAP8, DANCR, XIST, DLEU2, etc. are upregulated lncRNAs whereas GAS5, HMlincRNA717, MIAT, LINC01111, lncRNA KCNK15-AS1, etc. are downregulated lncRNAs inhibiting the invasion and progression of PDAC. These data provided helps in the assessment of lncRNAs in the development, metastasis, and occurrence of PDAC and also play a vital role in the evolution of biomarkers and therapeutic agents for the treatment of PDAC.

SUBMITTER: Ramya Devi KT

PROVIDER: S-EPMC8172159 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Long noncoding RNAs: role and contribution in pancreatic cancer.

Ramya Devi K T KT Karthik Dharshene D Mahendran TharunSelvam T Jaganathan M K MK Hemdev Sanjana Prakash SP

Transcription 20210201 1

Noncoding RNAs are proclaimed to be expressed in various cancer types and one such type is found to be pancreatic ductal adenocarcinoma (PDAC). The long noncoding RNAs (LncRNAs) affect the migration, invasion, and growth of tumor cells by playing important roles in the process of epigenesis, post-transcription, and transcriptional regulation along with the maintenance of apoptosis and cell cycle. It is quite subtle whether the alterations in lncRNAs would impact PDAC progression and development. ...[more]

PMID: 34036896

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Project description:"Pancreatic ductal adenocarcinoma (PDAC) is known by its aggressiveness and lack of effective therapeutic options. Thus, improvement in current knowledge of molecular changes associated with pancreatic cancer is urgently needed to explore novel venues of diagnostics and treatment of this dismal disease. While there is mounting evidence that long noncoding RNAs (ncRNAs) transcribed from intronic and intergenic regions of the human genome may play different roles in the regulation of gene expression in normal and cancer cells, their expression pattern and biological relevance in pancreatic cancer is currently unknown. In the present work we investigated the relative abundance of a collection of ncRNAs in patients’ pancreatic tissue samples aiming at identifying gene expression profiles correlated to pancreatic cancer and metastasis. To investigate the relative abundance, we used a custom 3,355-element spotted cDNA microarray interrogating protein-coding genes and putative ncRNA were used to obtain expression profiles from 38 clinical samples of tumor and non-tumor pancreatic tissues. Bioinformatics analyses were performed to characterize structure and conservation of ncRNAs expressed in pancreatic tissues, as well as to identify expression signatures correlated to tissue histology. Strand-specific reverse transcription followed by PCR and qRT-PCR were employed to determine strandedness of ncRNAs and to validate microarray results, respectively. We found that long intronic/intergenic ncRNAs are ubiquitously expressed across tumor and non-tumor pancreatic tissue samples. Enrichment of promoter-H3K4me3 associated chromatin marks and over-representation of conserved DNA elements and stable secondary structure predictions suggest that these transcripts are generated from independent transcriptional units and that at least a fraction is under evolutionary selection, and thus potentially functional. Statistically significant expression signatures comprising protein-coding mRNAs and long ncRNAs that correlate to PDAC or to pancreatic cancer metastasis were identified. Interestingly, loci harboring intronic ncRNAs differentially expressed in PDAC metastases were enriched in genes associated to the MAPK pathway. Orientation-specific RT-PCR documented that intronic transcripts are expressed in sense, antisense or both orientations relative to protein-coding mRNAs. Differential expression of a subset of intronic ncRNAs (PPP3CB, MAP3K14 and DAPK1 loci) in metastatic samples was confirmed by Real-Time PCR. All this results reveal sets of long intronic ncRNAs expressed in pancreatic tissues whose abundance is correlated to PDAC or metastasis, thus pointing to the potential relevance of this class of transcripts in biological processes related to malignant transformation and metastasis in pancreatic cancer. Fluorescent labeled cDNA targets derived from pancreatic tumor and non-tumor tissue from each patient were combined and hybridized to spotted cDNA microarrays. For each patient, a replicate hybridization was performed. For each sample, there are 4 replicate measurements for each probe. "

Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) is known by its aggressiveness and lack of effective therapeutic options. Thus, improvement in current knowledge of molecular changes associated with pancreatic cancer is urgently needed to explore novel venues of diagnostics and treatment of this dismal disease. While there is mounting evidence that long noncoding RNAs (lncRNAs) transcribed from intronic and intergenic regions of the human genome may play different roles in the regulation of gene expression in normal and cancer cells, their expression pattern and biological relevance in pancreatic cancer is currently unknown. In the present work we investigated the relative abundance of a collection of lncRNAs in patients' pancreatic tissue samples aiming at identifying gene expression profiles correlated to pancreatic cancer and metastasis.MethodsCustom 3,355-element spotted cDNA microarray interrogating protein-coding genes and putative lncRNA were used to obtain expression profiles from 38 clinical samples of tumor and non-tumor pancreatic tissues. Bioinformatics analyses were performed to characterize structure and conservation of lncRNAs expressed in pancreatic tissues, as well as to identify expression signatures correlated to tissue histology. Strand-specific reverse transcription followed by PCR and qRT-PCR were employed to determine strandedness of lncRNAs and to validate microarray results, respectively.ResultsWe show that subsets of intronic/intergenic lncRNAs are expressed across tumor and non-tumor pancreatic tissue samples. Enrichment of promoter-associated chromatin marks and over-representation of conserved DNA elements and stable secondary structure predictions suggest that these transcripts are generated from independent transcriptional units and that at least a fraction is under evolutionary selection, and thus potentially functional.Statistically significant expression signatures comprising protein-coding mRNAs and lncRNAs that correlate to PDAC or to pancreatic cancer metastasis were identified. Interestingly, loci harboring intronic lncRNAs differentially expressed in PDAC metastases were enriched in genes associated to the MAPK pathway. Orientation-specific RT-PCR documented that intronic transcripts are expressed in sense, antisense or both orientations relative to protein-coding mRNAs. Differential expression of a subset of intronic lncRNAs (PPP3CB, MAP3K14 and DAPK1 loci) in metastatic samples was confirmed by Real-Time PCR.ConclusionOur findings reveal sets of intronic lncRNAs expressed in pancreatic tissues whose abundance is correlated to PDAC or metastasis, thus pointing to the potential relevance of this class of transcripts in biological processes related to malignant transformation and metastasis in pancreatic cancer.

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Long noncoding RNAs: role and contribution in pancreatic cancer.

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Long noncoding RNAs: role and contribution in pancreatic cancer.

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