Antisense oligonucleotide repress telomerase activity via manipulating alternative splicing or translation.

Antisense oligonucleotide repress telomerase activity via manipulating alternative splicing or translation.
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反义寡核苷酸通过操纵选择性剪接或翻译来抑制端粒酶活性。

DOI:
10.1016/j.bbrc.2021.10.034
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发表时间:
2021-10
期刊:
Biochem Biophys Res Commun
影响因子:
--
通讯作者:
Wang Feng
Wang Feng
中科院分区:
其他
文献类型:
--
作者:
Zhou Junrui;Li Tingfang;Geng Xin;Sui Lei;Wang Feng

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Telomerase is a reverse transcriptase that catalyzes the addition of telomeric repeated DNA onto the 3′ ends of linear chromosomes. Telomerase inhibition was broadly used for cancer therapeutics. Here, six antisense oligonucleotides were designed to regulate TERT mRNA alternative splicing and protein translation. To pursue a better stability in vitro, we chemically modified the oligonucleotides into phosphorothioate (PS) backbone and 2′-O-methoxyethyl (2′-MOE PS) version and phosphoroamidate morpholino oligomer (PMO) version. The oligonucleotides were transfected into HEK 293T cells and HeLa cells, and the mRNA expression, protein level and catalytic activity of telomerase were determined. We found the Int8 notably promoted hTERT mRNA exon 7–8 skipping, which greatly reduced telomerase activity, and the 5′-UTR treatment led to an obvious protein translation barrier and telomerase inhibition. These results demonstrate the potential of antisense oligonucleotide drugs targeting hTERT for antitumor therapy. Moreover, two specific antisense oligonucleotides were identified to be effective in reducing telomerase activity.
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