High Expression of PKMYT1 Predicts Poor Prognosis and Aggravates the Progression of Osteosarcoma via the NF-& kappa;B Pathway in MG63 Cells

作者全名："Lu, Yang; Li, Ping; Zhou, Yuandong; Zhang, Jian"

作者地址："[Lu, Yang; Zhang, Jian] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped Surg, 1 Youyi Rd, Chongqing 400010, Peoples R China; [Lu, Yang] Chongqing Univ, Cent Hosp, Dept Plast Surg, 1 Jiangkang Rd, Chongqing 400010, Peoples R China; [Li, Ping] Chongqing Tradit Chinese Med Hosp, Dept Orthoped Surg, 6,Panxi Qizhi Rd, Chongqing 400021, Peoples R China; [Zhou, Yuandong] Peoples Hosp Chongqing Banan Dist, Dept Orthoped Surg, 659,Yunan Ave,Longzhouwan St, Chongqing 401320, Peoples R China"

通信作者："Lu, Y; Zhang, J (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped Surg, 1 Youyi Rd, Chongqing 400010, Peoples R China."

来源：CURRENT CANCER DRUG TARGETS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001014629600008

JCR分区：Q3

影响因子：2.3

年份：2023

卷号：23

期号：6

开始页：496

结束页：504

文献类型：Article

关键词：Osteosarcoma; PKMYT1; nuclear factor-& kappa;B; NF-& kappa;B; apoptosis; invasion ability

摘要："Background Protein kinase, membrane-associated tyrosine/threonine 1 (PKMYT1) contributes to the proliferative, migratory, invasive and colony-forming capabilities of oncocytes. Dysregulated expression of PKMYT1 is associated with numerous malignancies. However, at present, the functional role of PKMYT1 in osteosarcoma is still not clarified.Objective The present study, therefore, aimed to investigate the prognostic value of PKMYT1 in osteosarcoma, and to explore the underlying molecular mechanism(s).Methods To meet this end, the expression level of PKMYT1 in osteosarcoma was measured by immunohistochemical analysis. The prognostic value of PKMYT1 in osteosarcoma was analyzed on the basis of R2: Genomics Analysis and Visualization Platform. The functional role of PKMYT1 was subsequently investigated in MG63 cells by knocking down PKMYT1 expression via lentivirus encoding shRNA. MTT assay, scratch-wound and Transwell assays were then used to determine whether PKMYT1 fulfills a role in the proliferative and invasive capabilities of the MG63 cells. Subsequently, the role of PKMYT1 in the apoptosis of the cells was assessed using western blot and immunofluorescence analyses. Finally, to determine whether PKMYT1 exerts its role through the NF-?B pathway, fibroblast-stimulating lipopeptide-1 (FSL-1) was used as an NF-?B activator.Results Compared with normal tissues, osteosarcoma tissues showed a significantly increased level of PKMYT1 expression. The clinical survival analysis indicated that patients with high PKMYT1 expression were associated with lower probabilities of overall survival and metastasis-free survival compared with those with low PKMYT1 expression levels. Knockdown of PKMYT1 inhibited the migratory and invasive capabilities of the MG63 cells, and also facilitated their apoptosis. Moreover, the knockdown of PKMYT1 restrained the NF-?B pathway in MG63 cells, whereas activating the NF-?B pathway ameliorated the effects of silencing PKMYT1 on MG63 cells, suggesting that PKMYT1 functions via the NF-?B pathway in MG63 cells.Conclusion Taken together, the results of the present study have shown that a high expression level of PKMYT1 is associated with poor prognosis of osteosarcoma, and that PKMYT1 is able to aggravate the malignant progression of MG63 cells via negatively regulating the NF-?B pathway, suggesting that PKMYT1 may be a potential molecular therapeutic target for the treatment of osteosarcoma."

基金机构：Medical Research Project Chongqing Talents program [CQYC202010]

基金资助正文：This work was supported by the Medical Research Project of the Chongqing Talents program (Grant No. CQYC202010).