Title:High Expression of PKMYT1 Predicts Poor Prognosis and Aggravates the
Progression of Osteosarcoma via the NF-κB Pathway in MG63 Cells
Volume: 23
Issue: 6
Author(s): Yang Lu*, Ping Li, Yuandong Zhou and Jian Zhang*
Affiliation:
- Department of Orthopedics Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing Medical
University, No. 1 Youyi Road, Yuzhong, Chongqing, 400010, China
- Department of Plastic Surgery, Chongqing
University Central Hospital, Chongqing University, No. 1 Jiangkang Road, Yuzhong, Chongqing, 400010, China
- Department of Orthopedics Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing Medical
University, No. 1 Youyi Road, Yuzhong, Chongqing, 400010, China
Keywords:
Osteosarcoma, PKMYT1, nuclear factor-κB, NF-κB, apoptosis, invasion ability.
Abstract:
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-κB
pathway, fibroblast-stimulating lipopeptide-1 (FSL-1) was used as an NF-κB 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-κB pathway in MG63 cells, whereas activating the NF-
κB pathway ameliorated the effects of silencing PKMYT1 on MG63 cells, suggesting that PKMYT1
functions via the NF-κB 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-κB pathway, suggesting
that PKMYT1 may be a potential molecular therapeutic target for the treatment of osteosarcoma.
