Abstract
Dysregulation of histone demethylase Jumonji-C domain-containing protein 5 (JMJD5) has been identified as a great effect on tumorigenesis. Silibinin is a commonly used anti-hepatotoxic drug and exhibits anticancer effect in various cancers. However, the antitumor mechanism between silibinin and JMJD5 in oral squamous cell carcinoma (OSCC) remains unclear. In this study, the clinical significance of JMJD5 on OSCC patients was assessed through tissue microarray. Furthermore, mice bearing patient-derived tumor xenografts (PDTXs) and tongue cancer cell lines were treated with silibinin and evaluated for tumor growth and JMJD5 expression. High expression of JMJD5 in oral cancer was significantly associated with tumor size (P = 0.0241), cervical node metastasis (P = 0.0001) and clinical stage (P = 0.0002), was associated with worse survival rate compared with that of the total cohort (P = 0.0002). Collectively the data indicate that JMJD5 expression may be suitable for detection of unfavorable prognosis in OSCC patients, based in part on its apparent role as a marker of metastasis. In addition, silibinin inhibits cancer growth in vitro and in PDTX models. Furthermore, metastasis-associated protein 1 (MTA1) could regulate the expression for JMJD5 and had a positive correlation with JMJD5. Moreover, silibinin could downregulate JMJD5 and MTA1 in oral cancer. Present study thus identifies that JMJD5 might be an essential prognostic indicator and therapeutic target against OSCC progression. In addition, silibinin is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating JMJD5 in OSCC, through a mechanism likely involving MTA1/JMJD5 axis.
Highlights
Oral squamous cell carcinoma (OSCC) is a highly aggressive malignant tumor in the world [1, 2]
To determine the role of JMJD5 in oral cancer, the protein levels of JMJD5 and metastasis-associated protein 1 (MTA1) in 87 oral cancer and adjacent normal tissues were measured with IHC staining
OSCC cell lines revealed higher JMJD5 and MTA1 expression levels compared with normal human gingival fibroblast (Fig 1C)
Summary
Oral squamous cell carcinoma (OSCC) is a highly aggressive malignant tumor in the world [1, 2]. Novel prognostic factors and treatments are required to improve outcomes of patients with advanced oral cancer [1, 2]. One of the hallmarks of cancer cells is their altered metabolism [5], this generally involves an increased uptake of glucose. In this metabolic flux, the pyruvate kinase muscle isozyme 2 (PKM2) might play an important role [6]. Studies revealed that overexpression of PKM2 associates with aggressive clinicopathological features and unfavorable prognosis in OSCC [7, 8]. A study showed that Jumonji-C domain-containing protein 5 (JMJD5, KDM8) regulates nuclear translocation of PKM2 through direct physical binding and hinders the PKM2 tetrameric assembly and causes the nuclear translocation of PKM2 [9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
