Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer
Damage of mitochondrial functions caused by mitochondrial DNA (mtDNA) pathogenic mutations had long been proposed to be involved in breast carcinogenesis. However, the detailed pathological mechanism remained deeply undetermined. In this case-control study, we screened the frequencies of mitochondri...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Sciendo
2022-12-01
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| Series: | Balkan Journal of Medical Genetics |
| Subjects: | |
| Online Access: | https://doi.org/10.2478/bjmg-2022-0020 |
| _version_ | 1797796799096815616 |
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| author | Ding H.J. Zhao Y.P. Jiang Z.C. Zhou D.T. Zhu R. |
| author_facet | Ding H.J. Zhao Y.P. Jiang Z.C. Zhou D.T. Zhu R. |
| author_sort | Ding H.J. |
| collection | DOAJ |
| description | Damage of mitochondrial functions caused by mitochondrial DNA (mtDNA) pathogenic mutations had long been proposed to be involved in breast carcinogenesis. However, the detailed pathological mechanism remained deeply undetermined. In this case-control study, we screened the frequencies of mitochondrial tRNA (mt-tRNA) mutations in 80 breast cancer tissues and matched normal adjacent tissues. PCR and Sanger sequence revealed five possible pathogenic mutations: tRNAVal G1606A, tRNAIle A4300G, tRNASer(UCN) T7505C, tRNAGlu A14693G and tRNAThr G15927A. We noticed that these mutations resided at extremely conserved positions of tRNAs and would affect tRNAs transcription or modifications. Furthermore, functional analysis suggested that patients with these mt-tRNA mutations exhibited much lower levels of mtDNA copy number and ATP, as compared with controls (p<0.05). Therefore, it can be speculated that these mutations may impair mitochondrial protein synthesis and oxidative phosphorylation (OXPHOS) complexes, which caused mitochondrial dysfunctions that were involved in the breast carcinogenesis. Taken together, our data indicated that mutations in mt-tRNA were the important contributors to breast cancer, and mutational analyses of mt-tRNA genes were critical for prevention of breast cancer. |
| first_indexed | 2024-03-13T03:38:29Z |
| format | Article |
| id | doaj.art-6c0503849dd34152a4dc2550e4a657ba |
| institution | Directory Open Access Journal |
| issn | 2199-5761 |
| language | English |
| last_indexed | 2024-03-13T03:38:29Z |
| publishDate | 2022-12-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Balkan Journal of Medical Genetics |
| spelling | doaj.art-6c0503849dd34152a4dc2550e4a657ba2023-06-23T11:55:12ZengSciendoBalkan Journal of Medical Genetics2199-57612022-12-01252152210.2478/bjmg-2022-0020Analysis of Mitochondrial Transfer RNA Mutations in Breast CancerDing H.J.0Zhao Y.P.1Jiang Z.C.2Zhou D.T.3Zhu R.41School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China2Department of Pharmacy, Shaoxing Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Shaoxing, China3Department of Pathology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China4Department of Pharmacy, The First People’s Hospital of Kaili, Kaili, China1School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaDamage of mitochondrial functions caused by mitochondrial DNA (mtDNA) pathogenic mutations had long been proposed to be involved in breast carcinogenesis. However, the detailed pathological mechanism remained deeply undetermined. In this case-control study, we screened the frequencies of mitochondrial tRNA (mt-tRNA) mutations in 80 breast cancer tissues and matched normal adjacent tissues. PCR and Sanger sequence revealed five possible pathogenic mutations: tRNAVal G1606A, tRNAIle A4300G, tRNASer(UCN) T7505C, tRNAGlu A14693G and tRNAThr G15927A. We noticed that these mutations resided at extremely conserved positions of tRNAs and would affect tRNAs transcription or modifications. Furthermore, functional analysis suggested that patients with these mt-tRNA mutations exhibited much lower levels of mtDNA copy number and ATP, as compared with controls (p<0.05). Therefore, it can be speculated that these mutations may impair mitochondrial protein synthesis and oxidative phosphorylation (OXPHOS) complexes, which caused mitochondrial dysfunctions that were involved in the breast carcinogenesis. Taken together, our data indicated that mutations in mt-tRNA were the important contributors to breast cancer, and mutational analyses of mt-tRNA genes were critical for prevention of breast cancer.https://doi.org/10.2478/bjmg-2022-0020breast cancermitochondrial trnasmutationscarcinogenesispathogenicmitochondrial dysfunction |
| spellingShingle | Ding H.J. Zhao Y.P. Jiang Z.C. Zhou D.T. Zhu R. Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer Balkan Journal of Medical Genetics breast cancer mitochondrial trnas mutations carcinogenesis pathogenic mitochondrial dysfunction |
| title | Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer |
| title_full | Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer |
| title_fullStr | Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer |
| title_full_unstemmed | Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer |
| title_short | Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer |
| title_sort | analysis of mitochondrial transfer rna mutations in breast cancer |
| topic | breast cancer mitochondrial trnas mutations carcinogenesis pathogenic mitochondrial dysfunction |
| url | https://doi.org/10.2478/bjmg-2022-0020 |
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