| Citation: |
ZHANG Mingyue, CHEN Chen, WANG Meng, WANG Shouyu. Lnc-BM Promotes Gastric Cancer Progression by Regulating Mitochondrial Respiratory Function Through FASTK/MT-ND6 Axis[J]. Cancer Research on Prevention and Treatment, 2024, 51(4): 249-258. DOI: 10.3971/j.issn.1000-8578.2024.23.1335
|
To explore the role and molecular mechanism of Lnc-BM in the occurrence and development of gastric cancer (GC).
GC tissues and paired adjacent normal tissues of 36 GC patients were collected, and the expression of Lnc-BM was detected by RT-qPCR. Colony formation and CCK-8 assays were used to investigate the proliferation of GC cells. The migration and invasion properties of GC cells were investigated via Transwell assay. RNA pull-down assay was applied to confirm the interaction between FASTK and Lnc-BM. Western blot assay was used to detect FASTK protein level in Lnc-BM overexpressing or knockdown cells. Mitochondrial respiratory capacity and the related proteins expression levels were detected by Seahorse and Western blot assays, respectively. Lnc-BM stably overexpressing GC cells were constructed and then injected subcutaneously into nude mice. The tumor growth was observed.
Lnc-BM was highly expressed in GC tissues compared with their paired adjacent normal tissues. Lnc-BM overexpression significantly promoted GC cells proliferation migration and invasion, while Lnc-BM knockdown inhibited GC cells proliferation, migration and invasion (P < 0.05). RNA pull-down experiment demonstrated that Lnc-BM can directly bind to FASTK. Western blot results indicated that overexpression of Lnc-BM increased the protein levels of FASTK, while knockdown of Lnc-BM inhibited the expression of FASTK (P < 0.05). Compared to the control group, overexpression of Lnc-BM increased the levels of mitochondria associated proteins, such as MT-ND6 and TOM20 (P < 0.05). Seahorse results indicated that overexpression of Lnc-BM enhanced mitochondrial respiratory capacity (P < 0.05). Knocking down FASTK in Lnc-BM stably overexpressing cells can reverse the increase in mitochondrial respiratory capacity caused by Lnc-BM overexpression (P < 0.05). In vivo, the results of subcutaneously implanted tumor model in nude mouse showed that Lnc-BM overexpression promoted the tumor growth (P < 0.05).
Lnc-BM promotes GC progression by regulating mitochondrial respiratory function through the FASTK/MT-ND6 axis.
Competing interests: The authors declare that they have no competing interest.
| [1] |
Smyth EC, Nilsson M, Grabsch HI, et al. Gastric cancer[J]. Lancet, 2020, 396(10251): 635-648. doi: 10.1016/S0140-6736(20)31288-5
|
| [2] |
Joshi SS, Badgwell BD. Current treatment and recent progress in gastric cancer[J]. CA Cancer J Clin, 2021, 71(3): 264-279. doi: 10.3322/caac.21657
|
| [3] |
Chia NY, Tan P. Molecular classification of gastric cancer[J]. Ann Oncol, 2016, 27(5): 763-769. doi: 10.1093/annonc/mdw040
|
| [4] |
Malekos E, Carpenter S. Short open reading frame genes in innate immunity: from discovery to characterization[J]. Trends Immunol, 2022, 43(9): 741-756. doi: 10.1016/j.it.2022.07.005
|
| [5] |
Nojima T, Proudfoot NJ. Mechanisms of lncRNA biogenesis as revealed by nascent transcriptomics[J]. Nat Rev Mol Cell Biol, 2022, 23(6): 389-406. doi: 10.1038/s41580-021-00447-6
|
| [6] |
Wang S, Liang K, Hu Q, et al. JAK2-binding long noncoding RNA promotes breast cancer brain metastasis[J]. J Clin Invest, 2017, 127(12): 4498-4515. doi: 10.1172/JCI91553
|
| [7] |
Tan YQ, Zhang X, Zhang S, et al. Mitochondria: The metabolic switch of cellular oncogenic transformation[J]. Biochim Biophys Acta Rev Cancer, 2021, 1876(1): 188534. doi: 10.1016/j.bbcan.2021.188534
|
| [8] |
Ghezzi D, Saada A, D'Adamo P, et al. FASTKD2 nonsense mutation in an infantile mitochondrial encephalomyopathy associated with cytochrome c oxidase deficiency[J]. Am J Hum Genet, 2008, 83(3): 415-423. doi: 10.1016/j.ajhg.2008.08.009
|
| [9] |
Zhang F, Wang K, Zhang S, et al. Accelerated FASTK mRNA degradation induced by oxidative stress is responsible for the destroyed myocardial mitochondrial gene expression and respiratory function in alcoholic cardiomyopathy[J]. Redox Biol, 2021, 38: 101778. doi: 10.1016/j.redox.2020.101778
|
| [10] |
Arena G, Cissé MY, Pyrdziak S, et al. Mitochondrial MDM2 Regulates Respiratory Complex Ⅰ Activity Independently of p53[J]. Mol Cell, 2018, 69(4): 594-609.e8. doi: 10.1016/j.molcel.2018.01.023
|
| [11] |
Su J, Liu D, Yang F, et al. Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors[J]. Proc Natl Acad Sci U S A, 2022, 119(26): e2200158119. doi: 10.1073/pnas.2200158119
|
| [12] |
Guan WL, He Y, Xu RH. Gastric cancer treatment: recent progress and future perspectives[J]. J Hematol Oncol, 2023, 16(1): 57. doi: 10.1186/s13045-023-01451-3
|
| [13] |
Sainero-Alcolado L, Liaño-Pons J, Ruiz-Pérez MV, et al. Targeting mitochondrial metabolism for precision medicine in cancer[J]. Cell Death Differ, 2022, 29(7): 1304-1317. doi: 10.1038/s41418-022-01022-y
|
| [14] |
Arena G, Cissé MY, Pyrdziak S, et al. Mitochondrial MDM2 Regulates Respiratory Complex Ⅰ Activity Independently of p53[J]. Mol Cell, 2018, 69(4): 594-609. doi: 10.1016/j.molcel.2018.01.023
|
| [15] |
Sellin M, Mack R, Rhodes MC, et al. Molecular mechanisms by which splice modulator GEX1A inhibits leukaemia development and progression[J]. Br J Cancer, 2022, 127(2): 223-236. doi: 10.1038/s41416-022-01796-5
|
Figures(11)
This work is licensed under a Creative Commons Attribution 3.0 License.
Copyright © Editorial Department of Cancer Prevention Research 鄂公网安备 42011102005013号 鄂ICP备2022015867号
Supported by: Beijing Renhe Information Technology Co., Ltd. 
DownLoad: