Gao Feng, Yin Panpan, Wu Yanlin, Wen Jinlin, Su Ying, Zhang Xinyan
Beijing Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing, China.
J Oncol. 2021 Jan 12;2021:6644077. doi: 10.1155/2021/6644077. eCollection 2021.
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.
Ras同源家族成员C（RhoC）是细胞内信号转导的重要组成部分，据报道其过表达参与多种恶性肿瘤的肿瘤增殖、侵袭和转移调控。然而，其在口腔鳞状细胞癌（OSCC）中的作用及潜在机制仍不清楚。在我们的研究中，利用来自癌症基因组图谱（TCGA）的数据集分析了RhoC在OSCC中的表达、其与临床分期及生存率的关系。接下来，在体外建立了RhoC敲低细胞模型，并通过MTT法、集落形成试验、Transwell侵袭试验、划痕试验和F-肌动蛋白鬼笔环肽染色检测RhoC敲低对OSCC细胞的影响。建立了体内舌异种移植裸鼠模型，以检测RhoC敲低对肿瘤细胞生长和淋巴结转移的影响。通过实时PCR和免疫细胞化学进行机制研究。TCGA分析结果显示，RhoC在OSCC肿瘤组织中过表达。体外试验表明，RhoC敲低对OSCC细胞生长影响不大，但显著抑制细胞集落形成、侵袭和迁移能力，且F-肌动蛋白聚合也减少。体内舌异种移植模型表明，RhoC敲低抑制OSCC细胞生长并抑制向颈浅淋巴结转移。进一步的机制研究表明，RhoC敲低下调HMGA2表达，通过对TCGA数据集的分析发现，HMGA2表达与OSCC肿瘤组织中的RhoC表达高度相关。总体而言，我们的研究表明，RhoC敲低在体外抑制OSCC细胞侵袭和迁移，在体内抑制OSCC细胞生长和淋巴结转移。此外，这些活动涉及的潜在机制可能与HMGA2表达的调控有关。RhoC基因未来可能成为OSCC有前景的治疗靶点。
