ArticleNucleic acids research2022
Telomerase RNA TERC and the PI3K-AKT pathway form a positive feedback loop to regulate cell proliferation independent of telomerase activity.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Systems Biology and Experimental Validation Enable Discovery of MMP9-Centered Networks, Anticancer Activity, and Pharmacodynamic Signature in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2026Article
- Differential human telomerase RNA knockdown by antisense oligonucleotides reveals the existence and potential function of a robust RNA domain.RNA (New York, N.Y.) · 2026Article
- circHERC1-A telomerase activator.Science advances · 2025Article
- Chinese medicine boosts regenerative medicine in stem cell - based therapy.Stem cell research & therapy · 2025Review
- Aloe-emodin ameliorates chronic kidney disease fibrosis by inhibiting PI3K-mediated signaling pathway.European journal of histochemistry : EJH · 2025Article
- Overexpression of lncRNA TINCR inhibits cutaneous squamous cell carcinoma cells through promotes methylation of Myc and TERC genes.Archives of dermatological research · 2025Article
- Canonical and non-canonical functions of the non-coding RNA component (TERC) of telomerase complex.Cell & bioscience · 2025Review
- Telomeropathies in Interstitial Lung Disease and Lung Transplant Recipients.Journal of clinical medicine · 2025Review
- Telomeres, telomerase, and cancer: mechanisms, biomarkers, and therapeutics.Experimental hematology & oncology · 2025Review
- Telomerase in cancer- ongoing quest and future discoveries.Molecular biology reports · 2025Review
- Telomerase RNA component knockout exacerbateseLife · 2024Article
- TIN2 modulates FOXO1 mitochondrial shuttling to enhance oxidative stress-induced apoptosis in retinal pigment epithelium under hyperglycemia.Cell death and differentiation · 2024Article
- TERC promotes non-small cell lung cancer progression by facilitating the nuclear localization of TERT.iScience · 2024Article
- Precision Delivery of Human Bone Marrow-Derived Mesenchymal Stem Cells Into the Pancreas Via Intra-arterial Injection Prevents the Onset of Diabetes.Stem cells translational medicine · 2024Article
- Prevalence and Associations of Co-occurrence ofGlobal medical genetics · 2024Article
- Retinoic acid enhances ovarian steroidogenesis by regulating granulosa cell proliferation and MESP2/STAR/CYP11A1 pathway.Journal of advanced research · 2024Article
- Lactic acid promotes nucleus pulposus cell senescence and corresponding intervertebral disc degeneration via interacting with Akt.Cellular and molecular life sciences : CMLS · 2024Article
- Association of TERT (rs2736098 and rs2736100) genetic variants with elevated risk of hepatocellular carcinoma: a retrospective case-control study.Scientific reports · 2023Article
- Telomere Targeting Chimera Enables Targeted Destruction of Telomeric Repeat-Binding Factor Proteins.Journal of the American Chemical Society · 2023Article
- Many Functions of Telomerase Components: Certainties, Doubts, and Inconsistencies.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The core catalytic unit of telomerase comprises telomerase reverse transcriptase (TERT) and telomerase RNA (TERC). Unlike TERT, which is predominantly expressed in cancer and stem cells, TERC is ubiquitously expressed in normal somatic cells without telomerase activity. However, the functions of TERC in these telomerase-negative cells remain elusive. Here, we reported positive feedback regulation between TERC and the PI3K-AKT pathway that controlled cell proliferation independent of telomerase activity in human fibroblasts. Mechanistically, we revealed that TERC activated the transcription of target genes from the PI3K-AKT pathway, such as PDPK1, by targeting their promoters. Overexpression of PDPK1 partially rescued the deficiency of AKT activation caused by TERC depletion. Furthermore, we found that FOXO1, a transcription factor negatively regulated by the PI3K-AKT pathway, bound to TERC promoter and suppressed its expression. Intriguingly, TERC-induced activation of the PI3K-AKT pathway also played a critical role in the proliferation of activated CD4+ T cells. Collectively, our findings identify a novel function of TERC that regulates the PI3K-AKT pathway via positive feedback to elevate cell proliferation independent of telomerase activity and provide a potential strategy to promote CD4+ T cells expansion that is responsible for enhancing adaptive immune reactions to defend against pathogens and tumor cells.
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