Abstract
Telomerase is a ribonucleoprotein ribonucleic enzyme that elongates telomere repeat sequences at the ends of chromosomes and contributes to cellular immortalization. The catalytic component of telomerase, human telomerase reverse transcriptase (hTERT), has been observed to be reactivated in immortalized cells. Notably, most cancer cells have been found to have active hTERT mRNA transcription, resulting in continuous cell division, which is crucial for malignant transformation. Therefore, discovering mechanisms underlying the regulation of hTERT transcription is an attractive target for cancer-specific treatments.
Loss of heterozygosity (LOH) of chromosome 3p21.3 has been frequently observed in human oral squamous cell carcinoma (OSCC). Moreover, we previously reported that HSC3 OSCC microcell hybrid clones with an introduced human chromosome 3 (HSC3#3) showed inhibition of hTERT transcription compared with the parental HSC3 cells. This study examined whether hTERT transcription regulators are present in the 3p21.3 region. We constructed a human artificial chromosome (HAC) vector (3p21.3-HAC) with only the 3p21.3-p22.2 region and performed functional analysis using the 3p21.3-HAC. HSC3 microcell hybrid clones with an introduced 3p21.3-HAC exhibited significant suppression of hTERT transcription, similar to the microcell hybrid clones with an intact chromosome 3. In contrast, HSC3 clones with truncated chromosome 3 with deletion of the 3p21.3 region (3delp21.3) showed no effect on hTERT expression levels. These results provide direct evidence that hTERT suppressor gene(s) were retained in the 3p21.3 region, suggesting that the presence of regulatory factors that control telomerase enzyme activity may be involved in the development of OSCC.
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Data availability
The datasets created and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Change history
17 August 2023
A Correction to this paper has been published: https://doi.org/10.1007/s10577-023-09734-8
Abbreviations
- CYP3A :
-
Cytochrome P450 family 3 subfamily A
- DMD :
-
Duchenne muscular dystrophy
- DYS-HAC :
-
HAC vectors containing the entire dystrophin genomic region
- FISH :
-
Fluorescence in situ hybridization
- HAC :
-
Human artificial chromosome
- hTERT :
-
Human telomerase reverse transcriptase
- LOH :
-
Loss of heterozygosity
- MMCT :
-
Microcell-mediated chromosome transfer
- OSCC :
-
Oral squamous cell carcinoma
- RCC :
-
Renal cell carcinoma
- STS :
-
Sequence-tagged site
- 3p21.3-HAC :
-
HAC vector with only the 3p21.3-p22.2 region
- 3delp21.3 :
-
Truncated chromosome 3 with deletion of the 3p21.3 region
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This work was supported by the Japan Society for the Promotion of Science (JSPS) (Grant Number 19K10086 and 21K16213).
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T.O. and H. K. conceptualized the study, validated the data, performed formal analysis, and wrote the original draft. K. Y. provided the methodology and software and reviewed and edited the manuscript. H. K. performed project administration. H.K. acquired funding.
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Ohira, T., Yoshimura, K. & Kugoh, H. Human artificial chromosome carrying 3p21.3-p22.2 region suppresses hTERT transcription in oral cancer cells. Chromosome Res 31, 17 (2023). https://doi.org/10.1007/s10577-023-09726-8
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DOI: https://doi.org/10.1007/s10577-023-09726-8