This study identifies A10398G alteration of mitochondrial ND3 gene in plasma exosome of 29 non-small cell lung cancer (NSCLC) patients, 31 controls and 13 pairs of tumor tissue and adjacent tissue of NSCLC patients, thereby assessing the relationship between this alteration in plasma exosome and tissue as well as the pathological characteristics of NSCLC patients. Using the PCR-RFLP method, the homoplasmy and heteroplasmy of A10398G were initially identified in mitochondrial DNA from both exosomes and lung tissues. The rate of variant 10398G in plasma exosome was 62.1% in the NSCLC group and 61.3% in the control group. However, there was no statistically significant difference in A10398G between the patient and control groups. The alteration of A10398G in plasma exosome and in tissue correlated with each other (correlation coefficient 0.69; p = 0.009). However, this alteration was not related to age, gender, smoking, alcohol drinks status, tumor size, histological stage and TNM stage. Keywords A10398G alteration, mitochondrial DNA, plasma exosome, non-small cell lung cancer. References [1] Y. Zhang, Y. Liu, H. Liu, W.H. Tang, Exosomes: biogenesis, biologic function and clinical potential, Cell Biosci, 9 (2019) 19. https://doi.org/10.1186/s13578-019-0282-2.[2] H. Valadi, K. Ekström, A. Bossios, M. Sjöstrand, J.J. Lee, J.O. Lötvall, Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells, Nat Cell Biol, 9(6) (2007) 654–659. https://doi.org/10.1038/ncb1596.[3] A. Sharma & A. Johnson, Exosome DNA: Critical regulator of tumor immunity and a diagnostic biomarker, J Cell Physiol, 235(3) (2020) 1921–1932. https://doi.org/10.1002/jcp.29153.[4] Global Cancer Observatory, Cancer Today. https://gco.iarc.fr/today/online-analysis-pie. (accessed 05 November 2020).[5] A.A.M. Yusoff, F.N. Zulfakhar, S.Z.N.M. Khair, W.S.W. Abdullah, J.M. Abdullah, Z. Idris, Mitochondrial 10398A>G NADH-Dehydrogenase subunit 3 of complex I is frequently altered in intra-axial brain tumors in Malaysia, Brain Tumor Res Treat 6(1) (2018) 31–38. https://doi.org/10.14791/btrt.2018.6.e5.[6] P.T. Bich, N.N. Tu, N.T. Khuyen, Đ.M. Ha, T.V. To, T.H. Thai, The A10398G Alteration of Mitochondrial ND3 gene in Colorectal Cancer Patients, VNU Journal of Science: Medical and Pharmaceutical Sciences 34(2) (2018) 68. https://doi.org/10.25073/25881132/vnumps.4125. (in Vietnamese).[7] N.T.T. Linh, N.B. Hieu, Đ.M. Ha, T.V. To, T.H. Thai, Mitochondrial DNA A10398G Alteration in Breast Cancer Patients in Vietnam, VNU Journal of Science: Natural Sciences and Technology 31(2) (2015) 36. (in Vietnamese).[8] R.K. Bai, S.M. Leal, D. Covarrubias, A. Liu and L.J.C. Wong, Mitochondrial genetic background modifies breast cancer risk, Cancer Res 67(10) (2017) 4687-4694. https://doi.org/10.1158/0008-5472.CAN-06-3554.[9] J.A. Canter, A.R. Kallianpur, F.F. Parl, R.C. Millikan, Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women, Cancer Res 65(17) (2005) 8028-8033. https://doi.org/10.1158/0008-5472.can-05-1428.[10] K. Darvishi, S. Sharma, A.K. Bhat, E. Rai, R.N.K. Bamezai, Mitochondrial DNA G10398A polymorphism imparts maternal Haplogroup N a risk for breast and esophageal cancer, Cancer Letts 249(2) (2017) 249-255. https://doi.org/10.1016/j.canlet.2006.09.005.[11] S.H.H. Juo, M.Y. Lu, R.K. Bai, Y.C. Liao, R.B. Trieu, M.L. Yu, L.J.C Wong, A common mitochondrial polymorphism 10398A>G is associated metabolic syndrome in a Chinese population, Mitochondrion 10(3) (2010) 294-299. https://doi.org/10.1016/j.mito.2010.01.001.[12] H. Xu, W. He, H.G. Jiang, H. Zhao, X.H. Peng, Y.H. Wei, J.N. Wei, C.H. Xie, C. Liang, Y.H. Zhong, G. Zhang, D. Deng, Y.F. Zhou, F.X. Zhou, Prognostic value of mitochondrial DNA content and G10398A polymorphism in non-small cell lung cancer, Oncol Rep 30(6) (2013) 3006-3012. https://doi.org/10.3892/or.2013.2783.[13] Y. Qi, Y. Wei, Q. Wang, H. Xu, Y. Wang, A. Yao, H. Yang, Y. Gao, F. Zhou, Heteroplasmy of mutant mitochondrial DNA A10398G and analysis of its prognostic value in non-small cell lung cancer, Oncol Lett 12(5) (2016) 3081-3088. https://doi.org/10.3892/ol.2016.5086.[14] A.M. Czarnecka, T. Krawczyk, M. Zdrozny, J. Lubiński, R.S. Arnold, W. Kukwa, A. Scińska, P. Golik, E. Bartnik, J.A. Petros, Mitochondrial NADH-dehydrogenase subunit 3 (ND3) polymorphism (A10398G) and sporadic breast cancer in Poland, Breast Cancer Res Treat 121(2) (2010) 511-518. https://doi.org/10.1007/s10549-009-0358-5.[15] M. Guescini, S. Genedani, V. Stocchi & L. F.Agnati, Astrocytes and Glioblastoma cells release exosomes carrying mtDNA, J Neural Transm (Vienna), 117(1) (2010) 1–4. https://doi.org/10.1007/s00702-009-0288-8.[16] P. Sansone, C. Savini, I. Kurelac, Q. Chang, L.B. Amato, A. Strillacci, A. Stepanova, L. Iommarini, C. Mastroleo, L. Daly, A. Galkin, B.K. Thakur, N. Soplop, K. Uryu, A. Hoshino, L. Norton, M. Bonafé, M. Cricca, G. Gasparre, D. Lyden, and J. Bromberg, Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer, PNAS, 114(43) (2017) E9066-9075. https://doi.org/10.1073/pnas.1704862114.
Tóm tắt: Gen MT-ATP6 ty thể mã hóa cho tiểu đơn vị protein a, trung tâm của kênh proton của phức hệ tổng hợp ATP. Biến đổi của gen MT-ATP6 được cho là ảnh hưởng đến quá trình tổng hợp ATP và có liên quan với quá trình tạo u. Trong nghiên cứu này, biến đổi của gen MT-ATP6 được xác định trên 102 mẫu mô của bệnh nhân ung thư vú và 65 mẫu máu đối chứng sử dụng phương pháp PCR giải trình tự trực tiếp và PCR-RFLP, sau đó sử dụng các phương pháp phân tích thống kê để đánh giá mối liên quan giữa một số biến đổi điển hình với các đặc điểm bệnh học của ung thư vú. Kết quả đã xác định được 20 biến đổi của gen MT-ATP6 trên 35 mẫu mô u của bệnh nhân ung thư vú và 13 biến đổi trên 26 mẫu máu của người bình thường, trong đó có 12 biến đổi làm thay đổi trình tự axít amin và 1 biến đổi 9183insC chưa được công bố trước đây. Đa số các biến đổi có tần suất thấp từ 2,86% đến 5,71%. Các biến đổi làm thay đổi trình tự axít amin G9053A và G8584A với tần suất cao trên mẫu mô u được sàng lọc trong các mẫu nghiên cứu. Kết quả cho thấy tỉ lệ dạng biến đổi G9053A và G8584A tương ứng là 21,6% (22/102 trường hợp) và 24,5% (25/102 trường hợp) ở mô của bệnh nhân ung thư vú và 18,5% (12/65 trường hợp) ở mẫu máu của người bình thường. Tuy nhiên, không có sự khác biệt có ý nghĩa thống kê về tỉ lệ biến đổi G9053A và G8485A khi so sánh giữa nhóm bệnh nhân và đối chứng cũng như theo các đặc điểm bệnh học của ung thư vú như độ tuổi, kích thước khối u, số hạch, kích thước hạch, mức độ xâm lấn (giai đoạn T), mức độ hạch (giai đoạn N), mức độ biệt hóa của khối u và giai đoạn bệnh. Nghiên cứu này cho thấy biến đổi của gen MT-ATP6 khác nhau tùy thuộc vào từng nhóm bệnh nhân. Trên đối tượng bệnh nhân ung thư vú Việt Nam, tỉ lệ biến đổi G9053A và G8485A tương đối cao, tuy nhiên các biến đổi này không có mối liên hệ có ý nghĩa thống kê với bệnh ung thư vú. Từ khóa: ADN ty thể, MT-ATP6, Ung thư vú. . Phức hệ tổng hợp ATP (phức hệ V) là một enzyme sử dụng một dòng các proton đi qua màng trong của ty thể để tổng hợp nên ATP từ ADP. Nó bao gồm một phần nằm ở trên màng của ty thể (F 0 ) chứa Mở đầu
The silver nanoparticles (AgNPs) are synthesized by various methods and seem to be very hazardous to the ecosystem and expensive. Hence, the present study aimed to synthesize homogeneous silver nanoparticles (AgNPs) using Coccinia grandis (L.) Voigt leaf extract with procedures non-toxic, and eco-friendly. The formation of biologically synthesized AgNPs was characterized by UV-Visible spectrophotometer (UV-Vis) and the transmission electron microscope (TEM) techniques. The formation of the AgNPs was observed visually with the color change of the solution from yellow to reddish-brown. The UV-Vis spectroscopy showed the maximum absorbance wavelength of Ag0 at 469 nm. The TEM demonstrated AgNPs with an average particle diameter of 19.02 nm and clearly indicated the shape of AgNPs in solution is spherical and well dispersed. The density functional theory (DFT) studies reveal that the quercetin in Coccinia grandis (L.) Voigt leaf extract behaves as a reducing agent for the reduction of Ag+ ions into Ag0. This research opens up new options for the synthesis of size-controlled, large-scale, biocompatible using an inexpensive and non-toxic extract as a reducing and stabilizing agent.
For the prevalence of lung cancer and its poor diagnosis, the seeking of the efficient biomarkers for this disease is an urgent requirement, especially from non-invasive samples such as plasma. The mitochondria DNA (mtDNA) copy number change has been evaluated as a potential indicator of cancer risk, however, there have been few studies regarding mtDNA in plasma derived exosomes. In this study, the mtDNA copy number was measured on 29 plasma exosome samples of patients with non-small cell lung cancer (NSCLC) and 29 plasma exosome samples of cancer-free controls by real-time PCR assay, then being statistically analyzed to evaluate the relationship between these figures and several pathological features of NSCLC patients. As the results, the existence of mtDNA in exosomes isolated from plasma was detected through PCR assay using primers covering most of the mtDNA length. The relative mtDNA copy numbers determined in the exosomes of the disease and control groups were 1619.1 ± 2589.0 and 1207.0 ± 1550.0, respectively, whereas these values in two disease stages were 783.6 ± 759.3 (stage I-II) and 2647.0 ± 3584.0 (stage III-IV). Comparing among these groups, the difference was only statistically significant between the disease groups of stage I-II and stage III-IV (p<0.05), the group of stage III-IV and the control group (p<0.05). Indeed, the mtDNA copy number is associated with tumor stage and stage N (p<0.05). On the other aspect, the smoking habit of NSCLC patients could be an underlying reason behind the alteration in mtDNA copy number in the plasma exosomes. In short, our study demonstrates that the mtDNA copy number in exosomes resourced from plasma could be a potential biomarker for the detection and prognosis of NSCLC.
The MT-ATP8 gene encodes for A6L protein subunit belonging to the proton channel of the ATP synthase. MT-ATP8 gene’s mutations can affect the structure and function of the ATP synthase, which may cause diseases. In this study, alterations of MT-ATP8 gene were investigated in tumor tissues of patients with breast cancer and control blood samples using PCR combined with direct sequencing and PCR-RFLP methods, data were analyzed using bioinformatics tools and statistical methods. Sequencing results revealed 5 variants of MT-ATP8 gene on 35 breast tumor tissues and 26 blood samples of controls, of which two mutations C8414T and C8417T altered the amino acid sequence of the resulting protein. The C8417T was further screened by PCR-RFLP and was found in 0,98% (1/102) of breast tumor samples. This change lead to substitution of lecine to phenylalanine (L18F) in a highly conserved position of A6L and was predicted as probably damaging to the structure and function of the protein. Additionally, a 9 bp deletion was also observed in a non-coding region of mtDNA in 26,5% (27/102) of breast cancer patients and 27% (7/26) of controls. Thus, these results showed that C8417T variant in the conserved position of MT-ATP8 gene was rare and first identified in a group of breast cancer patients in Vietnam. Keywords Breast cancer, mitochondrial DNA, MT-ATP8 References [1] Petros JA, Baumann AK, Ruiz-Pesini E, Amin MB, Sun CQ, Hall J, Lim S, Issa MM, Flanders WD, Hosseini SH, Marshall FF, Wallace DC, mtDNA mutations increase tumorigenicity in prostate cancer, Proc Natl Acad Sci U S A (2005), 102(3):719-24.[2] Wang X, The expanding role of mitochondria in apoptosis, Genes Dev (2001), 15(22):2922-33.[3] Jonckheere AI, Smeitink JA, Rodenburg RJ, Mitochondrial ATP synthase: architecture, function and pathology, J Inherit Metab Dis (2012), 35(2):211-25.[4] Grzybowska-Szatkowska L, Slaska B, Rzymowska J, Brzozowska A, Florianczyk B, Novel mitochondrial mutations in the ATP6 and ATP8 genes in patients with breast cancer, Mol Med Rep (2014), 10(4):1772-8.[5] Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR, A method and server for predicting damaging missense mutations, Nat Methods (2010), 7(4):248-9.[6] Thapa S, Lalrohlui F, Ghatak S, Zohmingthanga J, Lallawmzuali D, Pautu JL, Senthil Kumar N, Mitochondrial complex I and V gene polymorphisms associated with breast cancer in mizo-mongloid population, Breast Cancer (2016), 23(4):607-16.[7] Warburg O, On the origin of cancer cells, Science (1956), 123:309-14.[8] Dumas JF, Rousse D, Servais S, Mitochondria and cancer, Cellular Bioenergetics in Health and Diseases: New Perspectives in Mitochondrial Biology (2012), 115-47.[9] Mkaouar-Rebai E, Kammoun F, Chamkha I, Kammoun N, Hsairi I, Triki C, Fakhfakh F, A de novo mutation in the adenosine triphosphatase (ATPase) 8 gene in a patient with mitochondrial disorder, J Child Neurol (2010), 25(6):770-5.[10] Jonckheere AI, Hogeveen M, Nijtmans LG et al., A novel mitochondrial ATP8 gene mutation in a patient with apical hypertrophic cardiomyopathy and neuropathy, J Med Genet (2008), 45:129-33.[11] Ware SM, El-Hassan N, Kahler SG et al., Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes, J Med Genet (2009), 46:308-14.[12] Liu VW, Shi HH, Cheung AN, Chiu PM, Leung TW, Nagley P, Wong LC, Ngan HY, High incidence of somatic mitochondrial DNA mutations in human ovarian carcinomas, Cancer Res (2001), 61(16):5998-6001.[13] Zhuo G, Feng G, Leng J, et al., A 9-bp deletion homoplasmy in women with polycystic ovary syndrome revealed by mitochondrial genome-mutation screen, Biochem Genet (2010), 48:157-163.[14] Abu-Amero KK, Alzahrani AS, Zou M, Shi Y, Association of mitochondrial DNA transversion mutations with familial medullary thyroid carcinoma/multiple endocrine neoplasia type 2 syndrome, Oncogene (2006), 25:677-84.[15] Bonora E, Porcelli AM, Gasparre G, et al., Defective oxidative phosphorylation in thyroid oncocytic carcinoma is associated with pathogenic mitochondrial DNA mutations affecting complexes I and III, Cancer Res (2006), 66:6087-96.[16] Costa-Guda J, Tokura T, Roth SI, Arnold A, Mitochondrial DNA mutations in oxyphilic and chief cell parathyroid adenomas, BMC Endocr Disord (2007); 7:8.[17] Chintha R, Kaipa PR, Sekhar N, Hasan Q, Mitochondria and tumors: A new perspective, Indian J Cancer (2013), 50(3).[18] Tan DJ, Bai RK, Wong LJ, Comprehensive scanning of somatic mitochondrial DNA mutations in breast cancer, Cancer Res (2002), 62(4):972-6.[19] Tipirisetti NR, Lakshmi RK, Govatati S, Govatati S, Vuree S, Singh L, Raghunadha Rao D, Bhanoori M, Vishnupriya S, Mitochondrial genome variations in advanced stage breast cancer: a case-control study, Mitochondrion (2013), 13(4):372-8. [20] Ghaffarpour M, Mahdian R, Fereidooni F, Kamalidehghan B, Moazami N, Houshmand M, The mitochondrial ATPase6 gene is more susceptible to mutation than the ATPase8 gene in breast cancer patients, Cancer Cell Int (2014), 14(1):21.[21] Perucca-Lostanlen D, Narbonne H, Hernandez JB, et al., Mitochondrial DNA variations in patients with maternally inherited diabetes and deafness syndrome, Biochem Biophys Res Commun (2000), 277(3):771-5.[22] Bai Y, Guo Z, Xu J, Zhang J, Cui L, Zhang H, Zhang S, The 9-bp deletion at position 8272 in region V of mitochondrial DNA is associated with renal cell carcinoma outcome, Mitochondrial DNA A DNA Mapp Seq Anal (2014), 27(3):1973-5.[23] Jin Y, Yu Q, Zhou D, Chen L, Huang X, Xu G, Huang J, Gao X, Gao Y, Shen L, The mitochondrial DNA 9-bp deletion polymorphism is a risk factor for hepatocellular carcinoma in the Chinese population, Genet Test Mol Biomarkers (2012), 16(5):330-4.[24] Ren W, Li Y, Li R, Feng H, Wu S, Mao Y, Huang L, Mitochondrial intergenic COII/tRNA(Lys) 9-bp deletion, a biomarker for hepatocellular carcinoma? Mitochondrial DNA A DNA Mapp Seq Anal (2015), 27(4):2520-2.[25] Cortopassi GA, Shibata D, Soong NW, Arnheim N, A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues, Proc Natl Acad Sci U S A (1992), 89(16):7370-4.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.