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The Up-Regulated Expression of Mitochondrial Membrane Molecule RHOT1 in Gastric Cancer Predicts the Prognosis of Patients and Promotes the Malignant Biological Behavior of Cells

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Abstract

Gastric cancer (GC) remains a major disease of high morbidity and mortality worldwide despite advances in diagnosis and treatment. Ras homolog family member T1 (RHOT1) plays an important role in several cancers. Our study aimed to analyze RHOT1 expression, to assess the relationship between its expression and the prognosis of patients, and know the impact of RHOT1 on GC cells. The Cancer Genome Atlas (TCGA) RNA-seq data was used for gene expression analysis, survival and prognostic analysis. Nomograms were created to analyze the pathological factors of GC patients. RHOT1 expression was up-regulated by analyzed TCGA-Stomach adenocarcinoma (STAD) data and verified by Polymerase Chain Reaction (PCR) assay in GC tissues and cell lines. Furthermore, RHOT1 up-regulation was significantly associated with shorter survival of GC patients. At last, after silencing the expression of RHOT1 in AGS cell lines, we found that the proliferative ability of the cells was significantly reduced, the cell invasion ability was significantly inhibited, the cell migration ability was also significantly weakened, the cell cycle was arrested in the G0/G1 phase, and apoptosis was significantly increased. So RHOT1 could impact the apoptosis, proliferation, invasion, and migration behavior of GC cells. We trust RHOT1 has the potential to become a new oncogene biomarker for diagnosis and prognosis as well as a new therapeutic target in GC.

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Data availability

The original data in the manuscript were downloaded from the official websites of TCGA (https://portal.gdc.cancer.gov/) and GTEx (https://gtexportal.org/home/). TCGA and GTEx RNA-seq data in TPM format were obtained from UCSC XENA (https://xenabrowser.net/datapages/). Thanks to **antao Academic (www.xiantao.love) for providing the R language analysis platform.

Abbreviations

ACC:

Adrenocortical carcinoma

BLCA:

Bladder urothelial carcinoma

BRCA:

Breast invasive carcinoma

CESC:

Cervical squamous cell carcinoma and endocervical adenocarcinoma

CHOL:

Cholangiocarcinoma

COAD:

Colon adenocarcinoma

DLBC:

Lymphoid neoplasm diffuse large B-cell lymphoma

ESCA:

Esophageal carcinoma

GBM:

Glioblastoma multiforme

HNSC:

Head and neck squamous carcinoma

KICH:

Kidney chromophobe

KIRC:

Kidney renal clear cell carcinoma

KIRP:

Kidney renal papillary cell carcinoma

LAML:

Acute myeloid leukemia

LGG:

Lower grade glioma

LIHC:

Liver cancer

LUAD:

Lung adenocarcinoma

LUSC:

Lung squamous cell carcinoma

MESO:

Mesothelioma

OV:

Ovarian cancer

PAAD:

Pancreatic cancer

PCPG:

Pheochromocytoma & paraganglioma

PRAD:

Prostate cancer

READ:

Rectal cancer

SARC:

Sarcoma

SKCM:

Melanoma

STAD:

Stomach cancer

TGCT:

Testicular cancer

THCA:

Thyroid cancer

THYM:

Thymoma

UCEC:

Endometrioid cancer

UCS:

Uterine carcinosarcoma

UVM:

Ocular melanomas

References

  1. Sung, H., & Ferlay, J. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209–249.

    PubMed  Google Scholar 

  2. Rezaei, Z., & Ranjbaran, J. (2022). Identification of early diagnostic biomarkers via WGCNA in gastric cancer. Biomedicine & Pharmacotherapy, 145, 112477.

    Article  CAS  Google Scholar 

  3. Karimi, P., & Islami, F. (2014). Gastric cancer: Descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiology, Biomarkers & Prevention, 23, 700–713.

    Article  Google Scholar 

  4. Hoshi, H. (2020). Management of gastric adenocarcinoma for general surgeons. Surgical Clinics of North America, 100, 523–534.

    Article  PubMed  Google Scholar 

  5. Swan, R., & Miner, T. J. (2006). Current role of surgical therapy in gastric cancer. World Journal of Gastroenterology, 12, 372–379.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Fransson, A., & Ruusala, A. (2003). Atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. Journal of Biological Chemistry, 278, 6495–6502.

    Article  CAS  PubMed  Google Scholar 

  7. Fransson, S., & Ruusala, A. (2006). The atypical Rho GTPases Miro-1 and Miro-2 have essential roles in mitochondrial trafficking. Biochemical and Biophysical Research Communications, 344, 500–510.

    Article  CAS  PubMed  Google Scholar 

  8. Macaskill, A. F., & Brickley, K. (2009). GTPase dependent recruitment of Grif-1 by Miro1 regulates mitochondrial trafficking in hippocampal neurons. Molecular and Cellular Neuroscience, 40, 301–312.

    Article  CAS  PubMed  Google Scholar 

  9. Wang, X., & Winter, D. (2011). PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell, 147, 893–906.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jiang, H., & He, C. (2012). RhoT1 and Smad4 are correlated with lymph node metastasis and overall survival in pancreatic cancer. PLoS ONE, 7, e42234.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  11. Li, Q., & Yao, L. (2015). Role of RHOT1 on migration and proliferation of pancreatic cancer. American Journal of Cancer Research, 5, 1460–1470.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Agarwal, E., & Altman, B. J. (2019). Myc regulation of a mitochondrial trafficking network mediates tumor cell invasion and metastasis. Molecular and Cellular Biology, 39, e00109-119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Peng, Y. Y., & Sun, D. (2022). Hsa_circ_0005230 is up-regulated and promotes gastric cancer cell invasion and migration via regulating the miR-1299/RHOT1 axis. Bioengineered, 13, 5046–5063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Guo, Q., & Zhao, L. (2023). Integrated pan-cancer analysis and experimental verification of the roles of tropomyosin 4 in gastric cancer. Frontiers in Immunology, 14, 1148056.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Shi, Y., & Wang, Y. (2023). Crosstalk of ferroptosis regulators and tumor immunity in pancreatic adenocarcinoma: Novel perspective to mRNA vaccines and personalized immunotherapy. Apoptosis, 28, 1423–1435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Liu, J., & Lichtenberg, T. (2018). An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics. Cell, 173, 400–416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ji, X., & Lee, Y. J. (2022). Characterization of cell cycle and apoptosis in Chinese hamster ovary cell culture using flow cytometry for bioprocess monitoring. Biotechnology Progress, 38, e3211.

    Article  CAS  PubMed  Google Scholar 

  18. Fox, M. H. (1980). A model for the computer analysis of synchronous DNA distributions obtained by flow cytometry. Cytometry, 1, 71–77.

    Article  CAS  PubMed  Google Scholar 

  19. Conti, C. B., & Agnesi, S. (2023). Early Gastric cancer: update on prevention, diagnosis and treatment. International Journal of Environmental Research and Public Health, 20, 2149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Huang, X., & Liu, Y. (2023). CHSY3 promotes proliferation and migration in gastric cancer and is associated with immune infiltration. Journal of Translational Medicine, 21, 474.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yu, J., & Feng, H. (2023). VPS35 promotes cell proliferation via EGFR recycling and enhances EGFR inhibitors response in gastric cancer. eBioMedicine, 89, 104451.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang, R., & Huang, W. (2023). FLOT1 promotes gastric cancer progression and metastasis through BCAR1/ERK signaling. International Journal of Biological Sciences, 19, 5104–5119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lopez-Domenech, G., & Covill-Cooke, C. (2018). Miro proteins coordinate microtubule- and actin-dependent mitochondrial transport and distribution. EMBO Journal, 37, 321–336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Safiulina, D., & Kuum, M. (2019). Miro proteins prime mitochondria for Parkin translocation and mitophagy. EMBO Journal, 38, e99384.

    Article  PubMed  Google Scholar 

  25. Weihofen, A., & Thomas, K. J. (2009). Pink1 forms a multiprotein complex with Miro and Milton, linking Pink1 function to mitochondrial trafficking. Biochemistry, 48, 2045–2052.

    Article  CAS  PubMed  Google Scholar 

  26. Grossmann, D., & Berenguer-Escuder, C. (2019). Mutations in RHOT1 disrupt endoplasmic reticulum-mitochondria contact sites interfering with calcium homeostasis and mitochondrial dynamics in Parkinson’s disease. Antioxidants & Redox Signaling, 31, 1213–1234.

    Article  CAS  Google Scholar 

  27. Birsa, N., & Norkett, R. (2014). Lysine 27 ubiquitination of the mitochondrial transport protein Miro is dependent on serine 65 of the Parkin ubiquitin ligase. Journal of Biological Chemistry, 289, 14569–14582.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hsieh, C. H., & Li, L. (2019). Miro1 marks Parkinson’s disease subset and miro1 reducer rescues neuron loss in Parkinson’s models. Cell Metabolism, 30, 1131–1140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schwarz, L., & Fitzgerald, J. C. (2022). Steady-state levels of miro1 linked to phosphorylation at serine 156 and mitochondrial respiration in dopaminergic neurons. Cells, 11, 1269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This study was supported by the Doctoral Start-up Foundation of Liaoning Province, China (2022-BS-340); and the Supporting Project for Undergraduate Research project of Shenyang Medical College, China (20229010).

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Authors and Affiliations

  1. Shenyang Medical College, Shenyang, Liaoning, People’s Republic of China

    Fanhao Kong, Siwen Yang & Ruimeng Shi

  2. Department of Histology and Embryology, Shenyang Medical College, Shenyang, Liaoning, People’s Republic of China

    Yanyu Peng

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  1. Fanhao Kong
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Correspondence to Yanyu Peng.

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This is an observational study. The Shenyang Medical College Research Ethics Committee has confirmed that no ethical approval is required.

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Kong, F., Yang, S., Shi, R. et al. The Up-Regulated Expression of Mitochondrial Membrane Molecule RHOT1 in Gastric Cancer Predicts the Prognosis of Patients and Promotes the Malignant Biological Behavior of Cells. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-024-01107-8

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  • DOI: https://doi.org/10.1007/s12033-024-01107-8

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