Details

Autor(en) / Beteiligte

• Zhou, Junrui
• Li, Tingfang
• Geng, Xin
• Sui, Lei
• Wang, Feng

Titel

Antisense oligonucleotide repress telomerase activity via manipulating alternative splicing or translation

Ist Teil von

• Biochemical and biophysical research communications, 2021-12, Vol.582, p.118-124

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. •Antisense oligo targeting hTERT could be used to repress telomerase activity.•Two AOs were selected to suppress telomerase at splicing and translation level.•The phosphoroamidate morpholino oligomer was more stable and efficient.