The Expression of SIRT1 and DBC1 in Laryngeal and Hypopharyngeal Carcinomas

Abstract

Rationale and ObjectiveSirtuin 1 (SIRT1) plays an important role in tumorigenesis and is increased in many human tumors. DBC1 is a negative regulator of SIRT1 via promotion of p53-mediated apoptosis. It is necessary to investigate the expression of SIRT1 and DBC1 in laryngeal and hypopharyngeal squamous cell carcinomas (LSCC and HSCC) and its correlation with available clinical parameters.MethodsThe mRNA levels of SIRT1 and DBC1 were measured in 54 paired LSCC or HSCC tumors and corresponding adjacent noncancerous mucosae using quantitative RT-PCR (qRT-PCR). The protein levels of SIRT1 and DBC1 were also evaluated in 120 cases of patients with LSCC or HSCC using immunohistochemical staining. The correlation between SIRT1 and DBC1 expression and clinical parameters was analyzed with Pearson chi-square test.ResultsqRT-PCR assay showed that, compared with the paired adjacent noncancerous mucosae, SIRT1 mRNA was significantly decreased in tumors. The immunohistochemical results indicated that the SIRT1 protein was also downregulated in tumors compared with noncancerous mucosae. Moreover, decreased SIRT1 was significantly correlated with the tumor clinical stage and lymph node metastasis. Additionally, DBC1 mRNA was significantly increased in tumors compared with noncancerous mucosae. The immunohistochemical results indicated that the DBC1 protein was downregulated in tumors, which is inconsistent with the results obtained by qRT-PCR. Finally, decreased DBC1 protein was significantly correlated with tumor differentiation, lymph node metastasis, and p53 expression.ConclusionsSIRT1 and DBC1 might be involved in the pathophysiology of laryngeal and hypopharyngeal squamous cell carcinomas and are associated with lymph node metastasis and p53 positive staining in LSCCs and HSCCs.

CCAR2 Is Required for Proliferation and Tumor Maintenance in Human Squamous Cell Carcinoma

“…Indeed, regulation of p53 by CCAR2 appears to be important for tumor initiation in some tissues, as Ccar2 −/− mice have increased tumor incidence compared to wild-type controls, dependent on p53 but Sirt -independent (Qin et al , 2015). In contrast to this data, many tumor types have been reported to have high expression of CCAR2, and this correlates with poor clinical outcomes (Cha et al , 2009; Cho et al , 2015; Kim et al , 2013; Kim et al , 2012; Yu et al , 2015; Yu et al , 2013; Zhang et al , 2014). In addition, the large majority of SCC tumors have mutated or lost p53 (Giglia-Mari and Sarasin, 2003), while CCAR2 is rarely altered in human cancer (Cerami et al , 2012), suggesting there may be p53-independent roles for CCAR2 in SCC.…”

“…In addition, the large majority of SCC tumors have mutated or lost p53 (Giglia-Mari and Sarasin, 2003), while CCAR2 is rarely altered in human cancer (Cerami et al , 2012), suggesting there may be p53-independent roles for CCAR2 in SCC. In this context, we sought to examine the requirement for CCAR2 in established SCC tumors, where high expression of CCAR2 is strongly correlated with poor clinical outcomes (Kim et al , 2012; Yu et al , 2013). Consistent with these reports, we find high levels of CCAR2 in human and mouse SCC compared to normal keratinocytes.…”

“…Clinical studies across a variety of tumor types, including SCC, have suggested that high levels of CCAR2 ( C ell C ycle activator and A poptosis R egulator 2; also known as DBC1) may be an indicator of poor outcomes (Chen et al , 2014; Kim et al , 2013; Kim et al , 2012; Yu et al , 2013), and could potentially have pro-tumorigenic functions. However, studies in Ccar2 − / − mice suggest that Ccar2 may function as a tumor-suppressor, although SCC did not develop in these mice (Qin et al , 2015).…”

Aberrant Expression of PHLPP1 and PHLPP2 Correlates with Poor Prognosis in Patients with Hypopharyngeal Squamous Cell Carcinoma

“…The poor prognosis of HSCC might be because of the lack of early detection and high rate of metastasis [ 3 ]. Many molecules, such as SIRT1, DBC1 [ 4 ], Beclin-1, LC3 [ 5 ], and Caveolin-1 [ 6 ], have been evaluated as candidate biomarkers for HSCC, but none have been widely used in practice because of the lack of understanding of the molecular mechanisms involved in HSCC development, progression, and treatment response [ 7 ]. Therefore, studies of novel and more effective molecular biomarkers of HSCC prognosis and progression are necessary.…”

Novel circular RNA expression profiles reflect progression of patients with hypopharyngeal squamous cell carcinoma

“…Hypopharyngeal squamous cell carcinoma (HSCC) is characterized by poor differentiation and early metastasis and is one of the most aggressive head and neck squamous cell carcinomas. Patients with HSCC are typically diagnosed with advanced-stage disease that is associated with a poor prognosis [ 1 ]. Despite improvements in comprehensive treatment strategies in recent years (including surgery, radiation therapy, and chemotherapy), patients with HSCC are still vulnerable to disease relapse, and the 5-year survival rate ranges from 25% to 40% [ 2 ].…”