Abstract
Accumulation of mitochondrial DNA (mtDNA) mutations has been proposed to contribute to the initiation and progression of tumors. By using high-throughput sequencing strategies, we measured 33 specimens including 11 hepatocellular carcinoma (HCC) tissues, 11 corresponding adjacent tissues, and 11 normal liver tissues. We identified 194 single nucleotide variants (SNVs; including insert and deletion) in 33 liver tissues, and 13 somatic novel mutations were detected, including 7 mutations in the coding region. One of the seven somatic mutations (T7609C, 91.09%) is synonymous, which does not change amino acid coding; the other four somatic mutations (T6115C, 65.74%; G8387A, 12.23%; G13121A, 93.08%; and T14180C, 28.22%) could result in amino acid substitutions, potentially leading to mitochondrial dysfunction. Furthermore, two mutations in tRNA might influence amino acid transportation. Consistent with a previous study, we also found that mtDNA copy number was significantly reduced in HCC tissues. Therefore, we established a mitochondrial genome depletion cell line ρ0 and revealed that mtDNA loss reduced proliferation and migration in HCC cells but promoted their resistance to 5-fluorouracil. Our results suggested that somatic mtDNA...Continue Reading
References
Aug 1, 1992·Nature Genetics·J M van den OuwelandJ A Maassen
May 1, 1992·Science·D C Wallace
Jun 15, 1990·Cell·J M ShoffnerD C Wallace
Dec 11, 1990·Nucleic Acids Research·G A Cortopassi, N Arnheim
Sep 1, 1988·Journal of Cellular Physiology·E D Robin, R Wong
Apr 9, 1981·Nature·S AndersonI G Young
Jan 1, 1994·Human Molecular Genetics·M SciaccoC T Moraes
Nov 5, 1997·The Journal of Biological Chemistry·D L Croteau, V A Bohr
Jan 10, 1998·Trends in Genetics : TIG·R N LightowlersN Howell
Nov 7, 1998·Nature Genetics·K PolyakB Vogelstein
Mar 5, 1999·Science·D C Wallace
Mar 17, 2000·Science·M S FlissD Sidransky
Jul 31, 2001·International Journal of Cancer. Journal International Du Cancer·E KirchesK Dietzmann
Aug 30, 2001·Oncogene·C JerónimoD Sidransky
Oct 3, 2003·Leukemia·L HeD M Turnbull
Nov 5, 2003·The Journal of Clinical Investigation·Robert W TaylorDouglass M Turnbull
Dec 9, 2003·The Journal of Biological Chemistry·Sun Young ParkMyung-Shik Lee
Dec 8, 2004·Journal of Gastroenterology·Akihiro TamoriMasayasu Inoue
Dec 21, 2004·Oncogene·Khaled K Abu-AmeroYufei Shi
Jan 14, 2005·Proceedings of the National Academy of Sciences of the United States of America·John A PetrosDouglas C Wallace
Mar 9, 2005·Cancer Research·Yujiro ShidaraShigeo Ohta
Apr 30, 2005·Nature Reviews. Genetics·Robert W Taylor, Doug M Turnbull
Nov 16, 2005·Annual Review of Genetics·Douglas C Wallace
Apr 5, 2008·Science·Kaori IshikawaJun-Ichi Hayashi
Jun 17, 2009·Biochimica Et Biophysica Acta·Wen-Yi HungHsin-Chen Lee
Dec 17, 2009·Mitochondrion·Pen-Hui YinHsin-Chen Lee
Sep 25, 2012·Nature Reviews. Cancer·Douglas C Wallace
Nov 17, 2012·Nature Reviews. Genetics·Eric A SchonMichio Hirano
Apr 20, 2014·World Journal of Gastroenterology : WJG·Hsin-Chen LeeChin-Wen Chi
May 27, 2014·Mitochondrion·Fei YeYan Guo
May 28, 2016·International Journal of Molecular Sciences·Chen-Sung LinYau-Huei Wei
Citations
May 8, 2019·Cells·Tommaso MelloAndrea Galli
Oct 11, 2019·Genome Biology and Evolution·Qi LiuYiqiang Zhao
Oct 19, 2019·Metabolites·Mélissa Léveillé, Jennifer L Estall
May 1, 2021·International Journal of Molecular Sciences·Miriam LongoPaola Dongiovanni
Nov 20, 2021·Frontiers in Oncology·Wan SunLixia Lu