دورية أكاديمية
Identification of mitochondrial RNA polymerase as a potential therapeutic target of osteosarcoma.
| العنوان: | Identification of mitochondrial RNA polymerase as a potential therapeutic target of osteosarcoma. |
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| المؤلفون: | Han QC; Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China., Zhang XY; Department of Orthopaedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Yan PH; Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China., Chen SF; Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China., Liu FF; Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China., Zhu YR; Department of Orthopedics, Affiliated Jiangyin Hospital of Medical College of Southeast University, Jiangyin, China. zyr13579@hotmail.com., Tian Q; Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China. jaytian2010@126.com. |
| المصدر: | Cell death discovery [Cell Death Discov] 2021 Dec 14; Vol. 7 (1), pp. 393. Date of Electronic Publication: 2021 Dec 14. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: United States NLM ID: 101665035 Publication Model: Electronic Cited Medium: Print ISSN: 2058-7716 (Print) Linking ISSN: 20587716 NLM ISO Abbreviation: Cell Death Discov Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [New York, NY] : Nature Publishing Group, [2015]- |
| مستخلص: | POLRMT (RNA polymerase mitochondrial) is essential for transcription of mitochondrial genome encoding components of oxidative phosphorylation process. The current study tested POLRMT expression and its potential function in osteosarcoma (OS). The Cancer Genome Atlas (TCGA) cohorts and Gene Expression Profiling Interactive Analysis (GEPIA) database both show that POLRMT transcripts are elevated in OS tissues. In addition, POLRMT mRNA and protein levels were upregulated in local OS tissues as well as in established and primary human OS cells. In different OS cells, shRNA-induced stable knockdown of POLRMT decreased cell viability, proliferation, migration, and invasion, whiling inducing apoptosis activation. CRISPR/Cas9-induced POLRMT knockout induced potent anti-OS cell activity as well. Conversely, in primary OS cells ectopic POLRMT overexpression accelerated cell proliferation and migration. In vivo, intratumoral injection of adeno-associated virus-packed POLRMT shRNA potently inhibited U2OS xenograft growth in nude mice. Importantly, levels of mitochondrial DNA, mitochondrial transcripts and expression of respiratory chain complex subunits were significantly decreased in U2OS xenografts with POLRMT shRNA virus injection. Together, POLRMT is overexpressed in human OS, promoting cell growth in vitro and in vivo. POLRMT could be a novel therapeutic target for OS. (© 2021. The Author(s).) |
| References: | Anderson ME. Update on Survival in Osteosarcoma. Orthop Clin North Am. 2016;47:283–92. (PMID: 2661494110.1016/j.ocl.2015.08.022) Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res. 2009;152:3–13. (PMID: 2021338310.1007/978-1-4419-0284-9_1) Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30. (PMID: 10.3322/caac.21590) Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34. (PMID: 3062040210.3322/caac.21551) Isakoff MS, Bielack SS, Meltzer P, Gorlick R. Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol. 2015;33:3029–35. (PMID: 26304877497919610.1200/JCO.2014.59.4895) Kansara M, Teng MW, Smyth MJ, Thomas DM. Translational biology of osteosarcoma. Nat Rev Cancer. 2014;14:722–35. (PMID: 2531986710.1038/nrc3838) Gill, J & Gorlick, R. Advancing therapy for osteosarcoma. Nat Rev Clin Oncol. 2021;18:609–24. Sayles LC, Breese MR, Koehne AL, Leung SG, Lee AG, Liu HY, et al. Genome-Informed Targeted Therapy for Osteosarcoma. Cancer Disco. 2019;9:46–63. (PMID: 10.1158/2159-8290.CD-17-1152) Shaikh AB, Li F, Li M, He B, He X, Chen G, et al. Present Advances and Future Perspectives of Molecular Targeted Therapy for Osteosarcoma. Int J Mol Sci. 2016;17:506. (PMID: 27058531484896210.3390/ijms17040506) Yang J, Zhang W. New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol. 2013;25:398–406. (PMID: 2366647110.1097/CCO.0b013e3283622c1b) Shi Y, Dierckx A, Wanrooij PH, Wanrooij S, Larsson NG, Wilhelmsson LM, et al. Mammalian transcription factor A is a core component of the mitochondrial transcription machinery. Proc Natl Acad Sci USA. 2012;109:16510–5. (PMID: 23012404347865710.1073/pnas.1119738109) Larsson NG, Wang J, Wilhelmsson H, Oldfors A, Rustin P, Lewandoski M, et al. Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet. 1998;18:231–6. (PMID: 950054410.1038/ng0398-231) Posse V, Al-Behadili A, Uhler JP, Clausen AR, Reyes A, Zeviani M, et al. RNase H1 directs origin-specific initiation of DNA replication in human mitochondria. PLoS Genet. 2019;15:e1007781. (PMID: 30605451631778310.1371/journal.pgen.1007781) Fuste JM, Wanrooij S, Jemt E, Granycome CE, Cluett TJ, Shi Y, et al. Mitochondrial RNA polymerase is needed for activation of the origin of light-strand DNA replication. Mol Cell. 2010;37:67–78. (PMID: 2012905610.1016/j.molcel.2009.12.021) Bralha FN, Liyanage SU, Hurren R, Wang X, Son MH, Fung TA, et al. Targeting mitochondrial RNA polymerase in acute myeloid leukemia. Oncotarget 2015;6:37216–28. (PMID: 26484416474192510.18632/oncotarget.6129) Salem AF, Whitaker-Menezes D, Howell A, Sotgia F, Lisanti MP. Mitochondrial biogenesis in epithelial cancer cells promotes breast cancer tumor growth and confers autophagy resistance. Cell Cycle. 2012;11:4174–80. (PMID: 23070475352421310.4161/cc.22376) Sotgia F, Whitaker-Menezes D, Martinez-Outschoorn UE, Salem AF, Tsirigos A, Lamb R, et al. Mitochondria “fuel” breast cancer metabolism: fifteen markers of mitochondrial biogenesis label epithelial cancer cells, but are excluded from adjacent stromal cells. Cell Cycle. 2012;11:4390–401. (PMID: 23172368355292210.4161/cc.22777) Bonekamp NA, Peter B, Hillen HS, Felser A, Bergbrede T, Choidas A, et al. Small-molecule inhibitors of human mitochondrial DNA transcription. Nature 2020;588:712–6. (PMID: 3332863310.1038/s41586-020-03048-z) Shan HJ, Zhu LQ, Yao C, Zhang ZQ, Liu YY, Jiang Q, et al. MAFG-driven osteosarcoma cell progression is inhibited by a novel miRNA miR-4660. Mol Ther Nucleic Acids. 2021;24:385–402. (PMID: 33868783803977610.1016/j.omtn.2021.03.006) Salvioli S, Ardizzoni A, Franceschi C, Cossarizza A. JC-1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to assess delta psi changes in intact cells: implications for studies on mitochondrial functionality during apoptosis. FEBS Lett. 1997;411:77–82. (PMID: 924714610.1016/S0014-5793(97)00669-8) Cossarizza A, Baccarani-Contri M, Kalashnikova G, Franceschi C. A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Biochem Biophys Res Commun. 1993;197:40–5. (PMID: 825094510.1006/bbrc.1993.2438) Weinberg SE, Chandel NS. Targeting mitochondria metabolism for cancer therapy. Nat Chem Biol. 2015;11:9–15. (PMID: 25517383434066710.1038/nchembio.1712) Ashton TM, McKenna WG, Kunz-Schughart LA, Higgins GS. Oxidative Phosphorylation as an Emerging Target in Cancer Therapy. Clin Cancer Res. 2018;24:2482–90. (PMID: 2942022310.1158/1078-0432.CCR-17-3070) Cavalli LR, Varella-Garcia M, Liang BC. Diminished tumorigenic phenotype after depletion of mitochondrial DNA. Cell Growth Differ. 1997;8:1189–98. (PMID: 9372242) Viale A, Corti D, Draetta GF. Tumors and mitochondrial respiration: a neglected connection. Cancer Res. 2015;75:3685–6. (PMID: 2637446310.1158/0008-5472.CAN-15-0491) Bosc C, Selak MA, Sarry JE. Resistance Is Futile: Targeting Mitochondrial Energetics and Metabolism to Overcome Drug Resistance in Cancer Treatment. Cell Metab. 2017;26:705–7. (PMID: 2911754510.1016/j.cmet.2017.10.013) Kuntz EM, Baquero P, Michie AM, Dunn K, Tardito S, Holyoake TL, et al. Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells. Nat Med. 2017;23:1234–40. (PMID: 28920959565746910.1038/nm.4399) Birsoy K, Possemato R, Lorbeer FK, Bayraktar EC, Thiru P, Yucel B, et al. Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides. Nature 2014;508:108–12. (PMID: 24670634401243210.1038/nature13110) Chaudhary S, Ganguly S, Palanichamy JK, Singh A, Bakhshi R, Jain A, et al. PGC1A driven enhanced mitochondrial DNA copy number predicts outcome in pediatric acute myeloid leukemia. Mitochondrion 2021;58:246–54. (PMID: 3381206110.1016/j.mito.2021.03.013) Oran AR, Adams CM, Zhang XY, Gennaro VJ, Pfeiffer HK, Mellert HS, et al. Multi-focal control of mitochondrial gene expression by oncogenic MYC provides potential therapeutic targets in cancer. Oncotarget 2016;7:72395–414. (PMID: 27590350534012410.18632/oncotarget.11718) Zhou Tong, Sang Yong-Hua, Cai Shang, Xu Chun, Shi Min-hua. The requirement of mitochondrial RNA polymerase for non-small cell lung cancer cell growth. Cell Death Dis. 2021;12:751. (PMID: 34326320832205810.1038/s41419-021-04039-2) Sotgia F, Martinez-Outschoorn UE, Lisanti MP. The reverse Warburg effect in osteosarcoma. Oncotarget 2014;5:7982–3. (PMID: 25478627422666010.18632/oncotarget.2352) Giang AH, Raymond T, Brookes P, de Mesy Bentley K, Schwarz E, O’Keefe R, et al. Mitochondrial dysfunction and permeability transition in osteosarcoma cells showing the Warburg effect. J Biol Chem. 2013;288:33303–11. (PMID: 24100035382917610.1074/jbc.M113.507129) Bonuccelli G, Avnet S, Grisendi G, Salerno M, Granchi D, Dominici M, et al. Role of mesenchymal stem cells in osteosarcoma and metabolic reprogramming of tumor cells. Oncotarget 2014;5:7575–88. (PMID: 25277190420214510.18632/oncotarget.2243) Dey R, Moraes CT. Lack of oxidative phosphorylation and low mitochondrial membrane potential decrease susceptibility to apoptosis and do not modulate the protective effect of Bcl-x(L) in osteosarcoma cells. J Biol Chem. 2000;275:7087–94. (PMID: 1070227510.1074/jbc.275.10.7087) Gao YY, Ling ZY, Zhu YR, Shi C, Wang Y, Zhang XY, et al. The histone acetyltransferase HBO1 functions as a novel oncogenic gene in osteosarcoma. Theranostics 2021;11:4599–615. (PMID: 33754016797829910.7150/thno.55655) Zhu YR, Xu Y, Fang JF, Zhou F, Deng XW, Zhang YQ. Bufotalin-induced apoptosis in osteoblastoma cells is associated with endoplasmic reticulum stress activation. Biochem Biophys Res Commun. 2014;451:112–8. (PMID: 2506899210.1016/j.bbrc.2014.07.077) Zhu YR, Min H, Fang JF, Zhou F, Deng XW, Zhang YQ. Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against osteosarcoma. Cancer Biol Ther. 2015;16:602–9. (PMID: 25869769462200810.1080/15384047.2015.1017155) Zhu YR, Zhou XZ, Zhu LQ, Yao C, Fang JF, Zhou F, et al. The anti-cancer activity of the mTORC1/2 dual inhibitor XL388 in preclinical osteosarcoma models. Oncotarget 2016;7:49527–38. (PMID: 27385099522652610.18632/oncotarget.10389) Zhuang Y, Wang S, Fei H, Ji F, Sun P. miR-107 inhibition upregulates CAB39 and activates AMPK-Nrf2 signaling to protect osteoblasts from dexamethasone-induced oxidative injury and cytotoxicity. Aging (Albany NY). 2020;12:11754–67. (PMID: 10.18632/aging.103341) Zhao S, Mao L, Wang SG, Chen FL, Ji F, Fei HD. MicroRNA-200a activates Nrf2 signaling to protect osteoblasts from dexamethasone. Oncotarget 2017;8:104867–76. (PMID: 29285219573960610.18632/oncotarget.20452) Cao C, Rioult-Pedotti MS, Migani P, Yu CJ, Tiwari R, Parang K, et al. Impairment of TrkB-PSD-95 signaling in Angelman syndrome. PLoS Biol. 2013;11:e1001478. (PMID: 23424281357055010.1371/journal.pbio.1001478) Cao C, Huang X, Han Y, Wan Y, Birnbaumer L, Feng GS, et al. Galpha(i1) and Galpha(i3) are required for epidermal growth factor-mediated activation of the Akt-mTORC1 pathway. Sci Signal. 2009;2:ra17. (PMID: 19401591413869910.1126/scisignal.2000118) |
| معلومات مُعتمدة: | 82002850 National Natural Science Foundation of China (National Science Foundation of China) |
| تواريخ الأحداث: | Date Created: 20211215 Latest Revision: 20230210 |
| رمز التحديث: | 20230211 |
| مُعرف محوري في PubMed: | PMC8671410 |
| DOI: | 10.1038/s41420-021-00780-x |
| PMID: | 34907167 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 2058-7716 |
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| DOI: | 10.1038/s41420-021-00780-x |