Long noncoding RNAs (lncRNAs), which are encoded by a vast less explored region of the human genome, may hold missing drivers of cancer and have gained attention recently as a potentially crucial layer of cancer cell regulation. lncRNAs are aberrantly expressed in a broad spectrum of cancers, and they play key roles in promoting and maintaining tumor initiation and progression, demonstrating their clinical potential as biomarkers and therapeutic targets. Recent discoveries have revealed that lncRNAs act as key signal transduction mediators in cancer signaling pathways by interacting with proteins, RNA, and lipids. Here, researchers at MD Anderson Cancer Center review the mechanisms by which lncRNAs regulate cellular responses to extracellular signals and discuss their clinical potential as diagnostic indicators, stratification markers, and therapeutic targets of combinatorial treatments.
Value of lncRNAs as Breast Cancer Risk Genes, Diagnostic Markers,
Prognostic Markers and Therapeutic Targets
lncRNAs as cancer risk genes: the search for genomic mutations related to lncRNAs suggests that disease-related SNP of lncRNAs may situate lncRNAs as cancer risk genes. Populations with the wild-type allele may exhibit low incidence of cancer; mutant allele carriers may show elevated incidence of cancer development. lncRNAs as diagnostic markers: the detection of lncRNAs in human blood, urine, or biopsy samples could be beneficial for risk detection in a gene carrier for early diagnosis of human cancer. lncRNAs as prognostic markers: the expression status of lncRNAs in human cancer tissues could be correlated with cancer stage, metastatic potential, resistance to target therapy, and patient outcome. The expression level of lncRNA could stratify cancer patients with target therapy. lncRNAs as therapeutic targets: antisense-oligonucleotide-based strategies are under development. siRNAs targeting lncRNAs could be encapsulated in nanoparticles for improved tissue distribution and pharmacodynamics. LNAs could also be the cargo of nanoparticles. Without delivery vehicles, LNAs exhibits adequate half-life in serum and tolerable toxicology.
Lin C, Yang L. (2017) Long Noncoding RNA in Cancer: Wiring Signaling Circuitry
. Trends Cell Biol
[Epub ahead of print]. [abstract