MiR-491-5p Reduces Telomerase-Immortalized Endothelial Cell Migration, Invasion and Angiogenesis by Inhibiting Telomerase Reverse Transcriptase Activity

Jiongwei Pan, Zaiting Ye, Xiaoping Cai, Hao Zheng, Yiwei Jiang, Xin Wang, Zhuo Cao

Article ID: 7234
Vol 37, Issue 4, 2023
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20233704.179
Received: 9 May 2023; Accepted: 9 May 2023; Available online: 9 May 2023; Issue release: 9 May 2023

Abstract

Background: Abnormal telomerase activity in cells is a warning sign of cancer. MiR-491-5p is related to a decline in telomerase activity, but the specific mechanism of action is still not clear. This study conducted research through bioassay combined with a series of molecular experiments. Methods: Bioassay was engineered to predict miR-491-5p binding site. The relationship between miR-491-5p and telomerase reverse transcriptase (TERT) was verified by double luciferase assay. Gene transfection assay was used to evaluate the miR-491-5p impact on telomerase activity via targeted genes. Cell viability, invasion, migration and angiogenesis were assessed by Cell Counting Kit-8 (CCK-8), Transwell, wound scratch and angiogenesis assays. Vascular endothelial growth factor (VEGF) expression levels and basic fibroblast growth factor (bFGF) in supernatant were tested exploiting ELISA (enzyme-linked immunosorbent assay). HIF-1α (hypoxia inducible factor-1α)/mTOR (mechanistic target of rapamycin) signaling pathway-related protein level were quantified with Western blotting. Results: TERT had a targeted binding relationship with miR-491-5p. Strengthened viability, invasion, angiogenesis and migration were found in telomerase-immortalized endothelial (TIVE) cells, which were reversed by miR-491-5p upregulation. TIVE cells showed telomerase activity, levels of VEGF, bFGF and HIF-1α upregulation as well as mTOR phosphorylation level, while overexpressed miR-491-5p inhibited the up-regulation of these changes in TIVE cells. Conclusions: MiR-491-5p reduced TIVE cell migration, viability, invasion and angiogenesis by inhibiting telomerase reverse transcriptase activity. Thus, targeting miR-491-5p might regulate the invasion, migration and angiogenesis of endothelial cells, thereby controlling tumors development.


Keywords

miR-491-5p;telomerase reverse transcriptase;migration;invasion;angiogenesis


References

Supporting Agencies



Copyright (c) 2023 Jiongwei Pan, Zaiting Ye, Xiaoping Cai, Hao Zheng, Yiwei Jiang, Xin Wang, Zhuo Cao




This site is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).