MYO1B as a prognostic biomarker and a therapeutic target in Arecoline-associated oral carcinoma
Zhen Sun
Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Search for more papers by this authorXiaopeng Guo
Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Search for more papers by this authorHuarong Chen
Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Search for more papers by this authorJunjun Ling
Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Search for more papers by this authorHouyu Zhao
Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Search for more papers by this authorCorresponding Author
Aoshuang Chang
Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Correspondence Aoshuang Chang and Xianlu Zhuo, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China.
Email: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Xianlu Zhuo
Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Correspondence Aoshuang Chang and Xianlu Zhuo, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China.
Email: [email protected] and [email protected]
Search for more papers by this authorZhen Sun
Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Search for more papers by this authorXiaopeng Guo
Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Search for more papers by this authorHuarong Chen
Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Search for more papers by this authorJunjun Ling
Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Search for more papers by this authorHouyu Zhao
Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Search for more papers by this authorCorresponding Author
Aoshuang Chang
Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Correspondence Aoshuang Chang and Xianlu Zhuo, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China.
Email: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Xianlu Zhuo
Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Correspondence Aoshuang Chang and Xianlu Zhuo, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China.
Email: [email protected] and [email protected]
Search for more papers by this authorZhen Sun and Xiaopeng Guo contributed equally to this study.
Abstract
Background
Arecoline, the main component of betel nut, induces malignant transformation of oral cells through complicated unclear mechanisms. Thus, we aimed to screen the key genes involved in Arecoline-induced oral cancer and further verify their expressions and roles.
Methods
This study included a data-mining part, a bioinformatics verification part, and an experimental verification one. First, the key gene related to oral cancer induced by Arecoline was screened. Then, the expression and clinical significance of the key gene in head and neck/oral cancer tissues were verified, and its downstream mechanisms of action were explored. Afterwards, the expression and roles of the key gene were verified by experiments at the histological and cytological levels.
Results
MYO1B was identified as the key gene. Overexpression of MYO1B was associated with lymph node metastasis and unfavorable outcomes in oral cancer. MYO1B may be mainly related to metastasis, angiogenesis, hypoxia, and differentiation. A positive correlation between MYO1B and the infiltration of macrophages, B cells, and dendritic cells was presented. MYO1B might have a close relationship with SMAD3, which may be enriched in the Wnt signaling pathway. MYO1B suppression markedly inhibited the proliferation, invasion, and metastasis abilities of both Arecoline-transformed oral cells and oral cancer cells.
Conclusion
This study revealed MYO1B as a key gene in Arecoline-induced oral tumorigenesis. MYO1B might be a novel prognostic indicator and therapeutic target for oral cancer.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
REFERENCES
- 1Neugebauer R, Fireman B, Roy JA, O'Connor PJ, Selby JV. Dynamic marginal structural modeling to evaluate the comparative effectiveness of more or less aggressive treatment intensification strategies in adults with type 2 diabetes. Pharmacoepidemiol Drug Safety. 2012; 21(suppl 2): 99-113.
- 2Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71(3): 209-249.
- 3Valdez JA, Brennan MT. Impact of oral cancer on quality of life. Dent Clin North Am. 2018; 62(1): 143-154.
- 4Inchingolo F, Santacroce L, Ballini A, et al. Oral cancer: A historical review. Int J Environ Res Public Health. 2020; 17(9): 3168.
- 5Zittel S, Moratin J, Horn D, et al. Clinical outcome and prognostic factors in recurrent oral squamous cell carcinoma after primary surgical treatment: a retrospective study. Clin Oral Investig. 2022; 26(2): 2055-2064.
- 6Carreras-Torras C, Gay-Escoda C. Techniques for early diagnosis of oral squamous cell carcinoma: systematic review. Medicina Oral Patología Oral y Cirugia Bucal. 2015; 20(3): e305-e315.
- 7Bauman JE, Zang Y, Sen M, et al. Prevention of Carcinogen-Induced oral cancer by sulforaphane. Cancer Prev Res. 2016; 9(7): 547-557.
- 8Arora S, Squier C. Areca nut trade, globalisation and its health impact: perspectives from India and south-east Asia. Perspectives in Public Health. 2019; 139(1): 44-48.
- 9Li YC, Cheng AJ, Lee LY, Huang YC, Chang JTC. Multifaceted mechanisms of areca nuts in oral carcinogenesis: the molecular pathology from precancerous condition to malignant transformation. J Cancer. 2019; 10(17): 4054-4062.
- 10Papke RL, Bhattacharyya I, Hatsukami DK, Moe I, Glatman S. Betel nut (areca) and smokeless tobacco use in Myanmar. Substance Use & Misuse. 2020; 55(9): 1385-1394.
- 11Oliveira NG, Ramos DL, Dinis-Oliveira RJ. Genetic toxicology and toxicokinetics of arecoline and related areca nut compounds: an updated review. Arch Toxicol. 2021; 95(2): 375-393.
- 12Jain V, Garg A, Parascandola M, Chaturvedi P, Khariwala SS, Stepanov I. Analysis of Alkaloids in Areca nut-containing products by liquid chromatography-tandem mass spectrometry. J Agricult Food Chem. 2017; 65(9): 1977-1983.
- 13Sharan RN, Mehrotra R, Choudhury Y, Asotra K. Association of betel nut with carcinogenesis: revisit with a clinical perspective. PLoS One. 2012; 7(8):e42759.
- 14Li X, Xie X, Gu Y, et al. Fat mass and obesity-associated protein regulates tumorigenesis of arecoline-promoted human oral carcinoma. Cancer Med. 2021; 10(18): 6402-6415.
- 15Ren H, He G, Lu Z, et al. Retracted:Arecoline induces epithelial-mesenchymal transformation and promotes metastasis of oral cancer by SAA1 expression. Cancer Sci. 2021; 112(6): 2173-2184.
- 16Islam S, Uehara O, Matsuoka H, et al. DNA hypermethylation of sirtuin 1 (SIRT1) caused by betel quid chewing-a possible predictive biomarker for malignant transformation. Clin Epigenetics. 2020; 12(1): 12.
- 17Kuo TM, Nithiyanantham S, Lee CP, et al. Arecoline N-oxide regulates oral squamous cell carcinoma development through NOTCH1 and FAT1 expressions. J Cell Physiol. 2019; 234(8): 13984-13993.
- 18Chuerduangphui J, Ekalaksananan T, Heawchaiyaphum C, Vatanasapt P, Pientong C. Peroxiredoxin 2 is highly expressed in human oral squamous cell carcinoma cells and is upregulated by human papillomavirus oncoproteins and arecoline, promoting proliferation. PLoS One. 2020; 15(12):e0242465.
- 19Clough E, Barrett T. The gene expression omnibus database. Methods Mol Biol. 2016; 1418: 93-110.
- 20Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res 2013; 41(Database issue): D991-D995.
- 21Huang D, Sherman BT, Tan Q, et al. The DAVID gene functional classification tool: a novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol. 2007; 8(9): R183.
- 22 The Gene Ontology C. The gene ontology resource: 20 years and still GOing strong. Nucleic Acids Res. 2019; 47(D1): D330-D338.
- 23Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017; 45(D1): D353-D361.
- 24Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019; 47(D1): D607-D613.
- 25Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014; 8(suppl 4): S11.
- 26Wang Z, Jensen MA, Zenklusen JC. A practical guide to the cancer genome Atlas (TCGA). Methods Mol Biol. 2016; 1418: 111-141.
- 27Li C, Tang Z, Zhang W, Ye Z, Liu F. GEPIA2021: integrating multiple deconvolution-based analysis into GEPIA. Nucleic Acids Res. 2021; 49(W1): W242-W246.
- 28Li T, Fu J, Zeng Z, et al. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 2020; 48(W1): W509-W514.
- 29Vasaikar SV, Straub P, Wang J, Zhang B. LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res. 2018; 46(D1): D956-D963.
- 30Miao YR, Zhang Q, Lei Q, et al. ImmuCellAI: a unique method for comprehensive T-Cell subsets abundance prediction and its application in cancer immunotherapy. Adv Sci. 2020; 7(7):1902880.
- 31Yuan H, Yan M, Zhang G, et al. CancerSEA: a cancer single-cell state Atlas. Nucleic Acids Res. 2019; 47(D1): D900-D908.
- 32Zhou G, Soufan O, Ewald J, Hancock REW, Basu N, Xia J. NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis. Nucleic Acids Res. 2019; 47(W1): W234-W241.
- 33Ling J, Chang A, Zhao H, Ye H, Zhuo X. EPHB2 as a recurrence-related gene and a prognostic indicator in nasopharyngeal carcinoma: A bioinformatics screening and immunohistochemistry verification. Histol Histopathol. 2022; 37(9): 889-897.
- 34Zhao H, Ling J, Huang Y, Chang A, Zhuo X. The expression and clinical significance of an Epithelial-Mesenchymal transition inducer, SNAI1, in head and neck carcinoma. J Oral Pathol Med. 2021; 50(2): 145-154.
- 35Chen Q, Jiao J, Wang Y, et al. Egr-1 mediates low-dose arecoline induced human oral mucosa fibroblast proliferation via transactivation of Wnt5a expression. BMC Molecular and Cell Biology. 2020; 21(1): 80.
- 36Wang TY, Peng CY, Lee SS, Chou MY, Yu CC, Chang YC. Acquisition cancer stemness, mesenchymal transdifferentiation, and chemoresistance properties by chronic exposure of oral epithelial cells to arecoline. Oncotarget. 2016; 7(51): 84072-84081.
- 37Tang YC, Hsiao JR, Jiang SS, et al. c-MYC-directed NRF2 drives malignant progression of head and neck cancer via glucose-6-phosphate dehydrogenase and transketolase activation. Theranostics. 2021; 11(11): 5232-5247.
- 38Feng S, Yuan W, Sun Z, et al. SPP1 as a key gene in the lymph node metastasis and a potential predictor of poor prognosis in head and neck carcinoma. J Oral Pathol Med. 2022; 51(7): 620-629.
- 39Ling J, Wang Y, Ma L, Chang A, Meng L, Zhang L. Exploration of potential targets and mechanisms of fisetin in the treatment of non-small-cell lung carcinoma via network pharmacology and in vitro validation. Evid Based Compl Altern Med. 2022; 2022:2383527.
- 40Warnakulasuriya S, Chen THH. Areca nut and oral cancer: evidence from studies conducted in humans. J Dent Res. 2022; 101: 1139-1146.
- 41Li YR, Yang WX. Myosins as fundamental components during tumorigenesis: diverse and indispensable. Oncotarget. 2016; 7(29): 46785-812.
- 42Zhu Y, Zheng S, Zhai X, et al. Comprehensive landscape of prognostic significance and immune characteristics of myosins in squamous cell carcinoma of the head and neck. J Immunol Res. 2022; 2022:5501476.
- 43Ohmura G, Tsujikawa T, Yaguchi T, et al. Aberrant myosin 1b expression promotes cell migration and lymph node metastasis of HNSCC. Mol Cancer Res. 2015; 13(4): 721-731.
- 44Xie L, Huang H, Zheng Z, et al. MYO1B enhances colorectal cancer metastasis by promoting the F-actin rearrangement and focal adhesion assembly via RhoA/ROCK/FAK signaling. Ann Transl Med. 2021; 9(20): 1543.
- 45Zhang HR, Lai SY, Huang LJ, et al. Myosin 1b promotes cell proliferation, migration, and invasion in cervical cancer. Gynecol Oncol. 2018; 149(1): 188-197.
- 46Wen LJ, Hu XL, Li CY, et al. Myosin 1b promotes migration, invasion and glycolysis in cervical cancer via ERK/HIF-1α pathway. Am J Transl Res. 2021; 13(11): 12536-12548.
- 47Gaglia MM, Munger K. More than just oncogenes: mechanisms of tumorigenesis by human viruses. Curr Opin Virol. 2018; 32: 48-59.
- 48Pietropaolo V, Prezioso C, Moens U. Role of Virus-Induced host cell epigenetic changes in cancer. Int J Mol Sci. 2021; 22(15): 8346.
- 49Padariya M, Kalathiya U, Mikac S, et al. Viruses, cancer and non-self recognition. Open Biol. 2021; 11(3):200348.
- 50Eckerling A, Ricon-Becker I, Sorski L, Sandbank E, Ben-Eliyahu S. Stress and cancer: mechanisms, significance and future directions. Nat Rev Cancer. 2021; 21(12): 767-785.
- 51Citro S, Miccolo C, Medda A, et al. HPV-mediated regulation of SMAD4 modulates the DNA damage response in head and neck cancer. J Exp Clin Cancer Res. 2022; 41(1): 59.
- 52Ghiani L, Chiocca S. High risk-human papillomavirus in HNSCC: present and future challenges for epigenetic therapies. Int J Mol Sci. 2022; 23(7): 3483.
- 53Wang S, Liu W, Ly D, Xu H, Qu L, Zhang L. Tumor-infiltrating B cells: their role and application in anti-tumor immunity in lung cancer. Cell Mol Immunol. 2019; 16(1): 6-18.
- 54Farhood B, Najafi M, Mortezaee K. CD8(+) cytotoxic T lymphocytes in cancer immunotherapy: a review. J Cell Physiol. 2019; 234(6): 8509-8521.
- 55Fu C, Jiang A. Dendritic cells and CD8 T cell immunity in tumor microenvironment. Front Immunol. 2018; 9: 3059.
- 56Pan Y, Yu Y, Wang X, Zhang T. Tumor-associated macrophages in tumor immunity. Front Immunol. 2020; 11:583084.
- 57Kou L, Huang H, Tang Y, et al. Opsonized nanoparticles target and regulate macrophage polarization for osteoarthritis therapy: a trapping strategy. J Controlled Release. 2022; 347: 237-255.
- 58Alamoud KA, Kukuruzinska MA. Emerging insights into Wnt/β-catenin signaling in head and neck cancer. J Dent Res. 2018; 97(6): 665-673.
- 59Paluszczak J. The significance of the dysregulation of canonical wnt signaling in head and neck squamous cell carcinomas. Cells. 2020; 9(3): 723.
- 60Sun H, Miao C, Liu W, et al. TGF-β1/TβRII/Smad3 signaling pathway promotes VEGF expression in oral squamous cell carcinoma tumor-associated macrophages. Biochem Biophys Res Commun. 2018; 497(2): 583-590.
- 61Xu M, Yin H, Cai Y, et al. Lysophosphatidic acid induces integrin β6 expression in human oral squamous cell carcinomas cells via LPAR1 coupling to Gαi and downstream SMAD3 and ETS-1 activation. Cell Signa. 2019; 60: 81-90.
