Long intergenic non‑coding RNA‑p21 mediates cardiac senescence via the Wnt/β‑catenin signaling pathway in doxorubicin-induced cardiotoxicity

Xie,Zhongdong; Xia,Wenzheng; Hou,Meng

doi:10.3892/mmr.2017.8169

Long intergenic non‑coding RNA‑p21 mediates cardiac senescence via the Wnt/β‑catenin signaling pathway in doxorubicin-induced cardiotoxicity

Authors:
- Zhongdong Xie
- Wenzheng Xia
- Meng Hou
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Affiliations: Department of General Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Neurosurgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Radiation Oncology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: November 28, 2017 https://doi.org/10.3892/mmr.2017.8169
Pages: 2695-2704

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Abstract

Doxorubicin (Dox)-induced cardiotoxicity has been a well‑known phenomenon to clinicians and scientists for decades. It has been confirmed that Dox‑dependent cardiotoxicity is accompanied by cardiac cellular senescence. However, the molecular mechanisms underlying Dox cardiotoxicity remains to be fully elucidated. Long non‑coding (lnc) RNAs regulate gene transcription and the fate of post‑transcriptional mRNA, which affects a broad range of age‑associated physiological and pathological conditions, including cardiovascular disease and cellular senescence. However, the functional role of lncRNAs in Dox‑induced cardiac cellular senescence remains largely unknown. Using the reverse transcription‑quantitative polymerase chain reaction method, the present study indicated that long intergenic non‑coding (linc) RNA‑p21 was highly expressed in Dox‑treated HL‑1 murine cardiomyocytes. Dox‑induced cardiac senescence was accompanied by decreased cellular proliferation and viability, increased expression of p53 and p16, and decreased telomere length and telomerase activity, while these effects were relieved by silencing endogenous lincRNA‑p21. We found that lincRNA‑p21 interacted with β‑catenin and that silencing β‑catenin abolished the anti‑senescent effect of lincRNA‑p21 silencing. It was observed that modulating lincRNA‑p21 to exert an anti‑senescent effect was dependent on decreasing oxidant stress. To conclude, the present findings suggest that lincRNA‑p21 may be involved in Dox‑associated cardiac cellular senescence and that silencing lincRNA‑p21 effectively protects against Dox cardiotoxicity by regulating the Wnt/β‑catenin signaling pathway and decreasing oxidant stress. Furthermore, modulating lincRNA‑p21 may have cardioprotective potential in patients with cancer receiving Dox treatment.

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