Researchers from Shahrekord University of Medical Sciences, Tehran University of Medical Sciences, and Babol University of Medical Sciences published a review on Apr. 11 discussing how pseudogene-derived long non-coding RNAs (lncRNAs) influence the behavior and signaling pathways of cancer stem cells.
Cancer stem cells are known to drive tumor initiation, progression, metastasis, relapse, and resistance to therapy because they can self-renew and differentiate. The mechanisms that control these cells remain poorly understood. However, recent findings suggest that non-coding RNAs—especially lncRNAs—play an important regulatory role in these processes.
The review focuses on pseudogene-derived lncRNAs. These transcripts were once considered "genomic artifacts" but are now recognized as active regulators similar to conventional lncRNAs. According to the researchers, these molecules impact cancer stem cell dynamics through mechanisms such as miRNA sponging, antisense regulation, and protein interactions.
Pseudogene-derived lncRNAs can act as competitive endogenous RNAs (ceRNAs), sponging microRNAs (miRNAs) to prevent them from binding their target messenger RNAs. This process affects gene expression after transcription. The review describes how these molecules influence key signaling pathways—including Wnt/β-catenin, PI3K/AKT, TGF-β, ERK, and JAK-STAT—that control survival and differentiation in cancer stem cells.
Specific examples detailed in the review include CYP4Z2P and RPSAP52 enhancing cancer stem cell traits in breast cancer and glioblastoma; RSU1P2/let-7a/Tex10 activating the Wnt/β-catenin pathway in liver cancer; PDIA3P1 interacting with OCT4 protein in esophageal squamous cell carcinoma; while TPTEP1, GUSBP11, AZGP1P2 suppress stemness traits in other cancers.
The authors note that levels of these lncRNAs correlate with tumor grade and patient outcomes. Researchers use RNA sequencing technologies along with bioinformatics tools for investigation followed by validation techniques such as RT-qPCR or FISH. They also employ CRISPR/Cas9 or siRNA-mediated modulation alongside biochemical assays like RIP or dual-luciferase reporters to map molecular interactions involved.
The review concludes by providing a comprehensive overview of how pseudogene-derived lncRNAs contribute both positively and negatively to the regulation of cancer stemness.
