Objective To analyze the LncRNA NEAT1/WTAP/MYC regulatory axis through bioinformatics analysis, and by knockdown LncRNA NEAT1 in osteosarcoma cells, explore its effects on cell proliferation, migration, invasion and apoptosis, and simultaneously detect the expression changes of key proteins (WTAP and MYC) of this signal axis. Methods Osteosarcoma hub genes were screened based on the TARGET database, the protein-protein interaction network was constructed by STRING, and the binding sites of NEAT1-miRNAs and the WTAP/MYC regulatory network were predicted by Starbase. si-NEAT1 was synthesized and transfected into 143B cells. After the knockdown efficiency was verified by RT-qPCR，proliferation was detected by MTT, migration/invasion was detected by Transwell, apoptosis was detected by flow cytometry, and the expression of WTAP/MYC proteins was detected by Western blot. Results Bioinformatics analysis revealed that NEAT1, as ceRNA, adsorbed miR-23a-3p/miR-150-5p to up-regulate WTAP, thereby promoting the expression of MYC; Knockdown of NEAT1 significantly inhibited the proliferation of osteosarcoma cells (P<0.001), migration/invasion (P<0.001), and promoted apoptosis (P<0.001); WB confirmed WTAP/MYC protein was significantly downregulated after knockdown (P<0.01). Conclusions Knockdown of LncRNA NEAT1 can inhibit the proliferation, migration, invasion of osteosarcoma cells and induce cell apoptosis. The mechanism may be related to the regulation of WTAP and MYC expression by LncRNA NEAT1. This study provides a theoretical basis for the mechanism research and targeted therapy of osteosarcoma.
Key words
WTAP /
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LncRNA NEAT1 /
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Osteosarcoma /
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MYC /
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SiRNA
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References
[1] Cole S, Gianferante DM, Zhu B, et al. Osteosarcoma: A Surveillance, Epidemiology, and End Results program-based analysis from 1975 to 2017[J]. Cancer, 2022, 128(11): 2107-2118. DOI:10.1002/cncr.34163.
[2] 许遵营, 吕海, 史本超, 等. TAp73和Beclin1在人骨肉瘤中表达及其临床意义[J]. 中国临床解剖学杂志, 2016, 34(1): 68-72. DOI:10.13418/j.issn.1001-165x.2016.01.018.
Xu ZY, Lv H, Shi BC,et al. Expression of TAp73 and Beclin1 in human osteosarcoma and their clinical significance[J].Chinese Journal of Clinical Anatomy, 2016, 34(1):68-72. DOI:10.13418/j.issn.1001-165x.2016.01.018.
[3] Zhang Q, Deng Z, Yang Y. Metastasis-Related Signature for Clinically Predicting Prognosis and Tumor Immune Microenvironment of Osteosarcoma Patients[J]. Mol Biotechnol, 2023, 65(11): 1836-1845. DOI:10.1007/s12033-023-00681-7.
[4] Ge J, Liu M, Zhang Y, et al. SNHG10/miR-141-3p/WTAP axis promotes osteosarcoma proliferation and migration[J]. J Biochem Mol Toxicol, 2022, 36(6): e23031. DOI:10.1002/jbt.23031.
[5] Yu Y, Wang S, Liu J, et al. Development and validation of a nomogram to predict long-term cancer-specific survival for patients with osteosarcoma[J]. Sci Rep, 2023, 13(1): 10230. DOI:10.1038/s41598-023-37391-8.
[6] Zhang TP, Li R, Wang LJ, et al. Roles of the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis[J]. Front Immunol, 2022, 992628: 1-13. DOI:10.3389/fimmu.2022.992628.
[7] Chen D, Wang J, Li Y, et al. LncRNA NEAT1 suppresses cellular senescence in hepatocellular carcinoma via KIF11-dependent repression of CDKN2A[J]. Clin Transl Med, 2023, 13(9): e1418. DOI:10.1002/ctm2.1418.
[8] Chen Y, Li J, Xiao J, et al. The lncRNA NEAT1 promotes the epithelial-mesenchymal transition and metastasis of osteosarcoma cells by sponging miR-483 to upregulate STAT3 expression[J]. Cancer Cell Int, 2021, 21(1): 90. DOI:10.1186/s12935-021-01780-8.
[9] Zhang Y, Luo M, Cui X, et al. Long noncoding RNA NEAT1 promotes ferroptosis by modulating the miR-362-3p/MIOX axis as a ceRNA[J]. Cell Death Differ, 2022, 29(9): 1850-1863. DOI:10.1038/s41418-022-00970-9.
[10]Liu F, Liao Z, Zhang Z. MYC in liver cancer: mechanisms and targeted therapy opportunities[J]. Oncogene, 2023, 42(45): 3303-3318. DOI:10.1038/s41388-023-02861-w.
[11]Cao P, Zhang W, Qiu J, et al. Gemcitabine Inhibits the Progression of Pancreatic Cancer by Restraining the WTAP/MYC Chain in an m6A-Dependent Manner[J]. Cancer Res Treat, 2024, 56(1): 259-271. DOI:10.4143/crt.2022.1600.
[12]Chen S, Li Y, Zhi S, et al. WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m6A-dependent manner[J]. Cell Death Dis, 2020, 11(8):659. DOI:10.1038/s41419-020-02847-6.
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