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Cell Based Assays of SINEUP Non-coding RNAs That Can Specifically Enhance mRNA Translation
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Capturing functional long non-coding RNAs through integrating large-scale causal relations from gene perturbation

Jinyuan Xu1, Aiai Shi1, Zhilin Long1

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

Ebiomedicine
|September 5, 2018
PubMed
Summary

This study introduces LnCAR, a computational method that identifies long noncoding RNA (lncRNA) functions by analyzing gene perturbation data. It reveals lncRNAs critical for cancer invasion, metastasis, and immune evasion, offering potential biomarkers for cancer progression and immunotherapy response.

Keywords:
CancerFunctionGene perturbationImmunotherapylncRNA

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Area of Science:

  • Genomics
  • Computational Biology
  • Cancer Research

Background:

  • Characterizing long noncoding RNA (lncRNA) functions is challenging due to limited understanding of their regulatory roles.
  • Gene perturbation expression profiles are valuable for inferring causal relationships between genes and their responses.

Purpose of the Study:

  • To develop a novel computational approach (LnCAR) for inferring lncRNA functions using large-scale gene perturbation data.
  • To identify lncRNAs involved in cancer hallmark processes and evaluate their clinical relevance.

Main Methods:

  • Annotated over 600 genome-wide gene perturbation profiles to identify >354,000 causal relationships involving lncRNAs.
  • Developed and applied the LnCAR computational approach to infer lncRNA functions, comparing its accuracy to co-expression methods.
  • Investigated the association of identified lncRNAs with cancer hallmarks, including invasion, metastasis, and immune evasion.

Main Results:

  • LnCAR demonstrated higher accuracy in inferring lncRNA functions compared to co-expression based approaches.
  • Identified 38 lncRNAs associated with distinct carcinogenic processes.
  • lncRNAs linked to "activating invasion & metastasis" predicted metastatic progression across various cancers.
  • lncRNAs related to "evading immune destruction" correlated with immune infiltration and predicted response to anti-PD-1 immunotherapy.

Conclusions:

  • The developed LnCAR approach offers a systematic method for revealing lncRNA functions.
  • Identified lncRNAs hold potential as biomarkers for cancer metastasis and predicting immunotherapy response.
  • This resource facilitates further experimental validation and clinical translation of lncRNA research.