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The multifaceted roles of long noncoding RNAs in pancreatic cancer: an update on what we know.

ABSTRACT: Pancreatic cancer (PC) is one of the leading causes of cancer-related deaths worldwide. Due to the shortage of effective biomarkers for predicting survival and diagnosing PC, the underlying mechanism is still intensively investigated but poorly understood. Long noncoding RNAs (lncRNAs) provide biological functional diversity and complexity in protein regulatory networks. Scientific studies have revealed the emerging functions and regulatory roles of lncRNAs in PC behaviors. It is worth noting that some in-depth studies have revealed that lncRNAs are significantly associated with the initiation and progression of PC. As lncRNAs have good properties for both diagnostic and prognostic prediction due to their translation potential, we herein address the current understanding of the multifaceted roles of lncRNAs as regulators in the molecular mechanism of PC. We also discuss the possibility of using lncRNAs as survival biomarkers and their contributions to the development of targeted therapies based on the literature. The present review, based on what we know about current research findings, may help us better understand the roles of lncRNAs in PC.

SUBMITTER: Zhou W

PROVIDER: S-EPMC7003405 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The multifaceted roles of long noncoding RNAs in pancreatic cancer: an update on what we know.

Zhou Wenjia W Chen Lu L Li Chao C Huang Rui R Guo Mian M Ning Shangwei S Ji Jingjing J Guo Xiaorong X Lou Ge G Jia Xinqi X Zhao Junjie J Luo Feng F Li Chunlong C Qu Zhaowei Z Yu Shan S Tai Sheng S

Cancer cell international 20200205

Pancreatic cancer (PC) is one of the leading causes of cancer-related deaths worldwide. Due to the shortage of effective biomarkers for predicting survival and diagnosing PC, the underlying mechanism is still intensively investigated but poorly understood. Long noncoding RNAs (lncRNAs) provide biological functional diversity and complexity in protein regulatory networks. Scientific studies have revealed the emerging functions and regulatory roles of lncRNAs in PC behaviors. It is worth noting th ...[more]

PMID: 32042268

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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. "

Dataset Information

The multifaceted roles of long noncoding RNAs in pancreatic cancer: an update on what we know.

Publications

The multifaceted roles of long noncoding RNAs in pancreatic cancer: an update on what we know.

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