Abstract
Ras homolog family member C (RhoC) is an important component of intracellular signal transduction and its overexpression has been reported to be involved in regulating tumor proliferation, invasion, and metastasis in various malignant tumors. However, its role and underlying mechanism in oral squamous cell carcinoma (OSCC) still remain obscure. In our study, RhoC expression, its relation with clinical stages, and survival rate in OSCC were analyzed using datasets from The Cancer Genome Atlas (TCGA). Next, a RhoC knockdown cell model was established in vitro, and the effects of RhoC knockdown in OSCC cells were detected by the MTT assay, colony formation assay, transwell invasion assay, scratch assay, and F-actin phalloidin staining. An in vivo tongue-xenografted nude mouse model was established to measure the effects of knockdown of RhoC on tumor cell growth and lymph node metastasis. A mechanism study was conducted by real-time PCR and immunocytochemistry. The results of TCGA analysis showed that RhoC was overexpressed in OSCC tumor tissues. In vitro assays indicated that knockdown of RhoC did not have much effect on OSCC cell growth but significantly suppressed cell colony formation, invasion, and migration abilities, and F-actin polymerization was also reduced. The tongue-xenografted in vivo model demonstrated that knockdown of RhoC suppressed OSCC cell growth and inhibited metastasis to the superficial cervical lymph nodes. Further mechanism studies showed that knockdown of RhoC downregulated HMGA2 expression, and HMGA2 expression was highly correlated with RhoC expression in OSCC tumor tissues via the analysis of TCGA datasets. Overall, our study showed that knockdown of RhoC inhibited OSCC cells invasion and migration in vitro and OSCC cell growth and lymph node metastasis in vivo. Moreover, the potential mechanisms involved in these activities may be related to the regulation of HMGA2 expression. The RhoC gene could serve as a promising therapeutic target for OSCCs in the future.
Highlights
Oral squamous cell carcinoma (OSCC) is the tenth leading cause of cancer-related deaths worldwide, reaching 145,400 deaths in 2012 [1]
Overall survival (OS) analysis indicated that patients with high Ras homolog family member C (RhoC) expression had poorer OS than cancer patients with lower RhoC expression, but the difference was not statistically significant (Figure 1(c), P 0.281). e above results indicated that RhoC was overexpressed in tumor tissues and the expression of RhoC correlated with tumor progression
Transfected cells were selected by puromycin treatment and the efficiency of knockdown of RhoC was detected by Real-Time Polymerase Chain Reaction (RT-PCR) and ICC. e RNA expression of RhoC in the RhoC/shRNA group was significantly lower than in the control group (Figure 2(c))
Summary
Oral squamous cell carcinoma (OSCC) is the tenth leading cause of cancer-related deaths worldwide, reaching 145,400 deaths in 2012 [1]. OSCC causes cervical lymph node metastasis due to the abundance of lymphatic vessels in the oral area [3]. E high OSCC mortality is considered strongly associated with the local invasive properties of tumor cells and with lymph node metastasis. Studies have shown that the abnormal activation of the Rho family of GTPases, components of the Ras homology protein family, plays a crucial role in a wide range of cell activities including cell proliferation, differentiation, apoptosis, cell adhesion, and invasive and metastatic potential of tumor cells [4, 5]. RhoC is increasingly reported to be involved in the malignant potential of tumors, such as breast cancer [7], lung cancer [8], gastric cancer [9], colon cancer [10], prostate cancer [11], and head and neck squamous cell carcinoma
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