Subpathway-LNCE: Identify dysfunctional subpathways competitively regulated by lncRNAs through integrating

Xinrui Shi1, Yanjun Xu1, Chunlong Zhang1

  • 1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.

Oncotarget
|September 17, 2016
PubMed

Insights

This study introduces Subpathway-LNCE, a novel method to identify long noncoding RNAs (lncRNAs) that regulate disease pathways. This tool helps uncover the roles of lncRNAs in diseases like cancer.

Area of Science:

  • Molecular Biology
  • Bioinformatics
  • Genomics

Background:

  • Long noncoding RNAs (lncRNAs) are increasingly recognized as crucial regulators in various diseases, including cancer.
  • lncRNAs can modulate messenger RNA (mRNA) stability and translation by competitively binding to microRNAs (miRNAs).
  • Understanding lncRNA-mediated regulatory networks is vital for deciphering disease mechanisms and identifying therapeutic targets.

Purpose of the Study:

  • To develop and validate an effective computational method, Subpathway-LNCE, for identifying lncRNA-competitively regulated subpathways.
  • To elucidate the functional roles of lncRNAs in disease pathogenesis through pathway analysis.
  • To provide a tool for uncovering disease-associated lncRNAs and their regulatory functions.

Main Methods:

  • Integration of lncRNA-mRNA expression profiles with pathway topology data.
  • Development of the Subpathway-LNCE algorithm to identify dysregulated subpathways driven by lncRNA-miRNA-mRNA interactions.
  • Application and validation of the method using datasets from prostate cancer, lung adenocarcinoma (LUAD), and kidney renal clear cell carcinoma.

Main Results:

  • Subpathway-LNCE successfully identified disease-associated dysfunctional subpathways regulated by lncRNAs in various cancer types.
  • The method demonstrated effectiveness in pinpointing key lncRNAs involved in kidney renal clear cell carcinoma.
  • The Subpathway-LNCE method was confirmed to be reproducible and robust across different datasets.

Conclusions:

  • Subpathway-LNCE offers a flexible and powerful approach to identify lncRNA-regulated signal subpathways in specific disease contexts.
  • The tool aids in understanding the functional significance of lncRNAs in disease progression and provides insights into potential therapeutic strategies.
  • An R package for Subpathway-LNCE is publicly available, facilitating broader research applications.

Related Concept Videos

lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
10.1K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

3.8K
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
9.0K
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
12.0K
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

3.6K
Types of RNA01:20

Types of RNA

Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA Performs Diverse...
10.2K