Knockdown of RhoC Inhibits Oral Squamous Cell Carcinoma Cell Invasion and Metastasis via Regulation of HMGA2

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.

Labio-Jugal Squamous Cell Carcinoma on HIV Site: Surgical Excision and Reconstruction with a Musculocutaneous Flap of the Pectoralis Major: A Case Report

“…HPV vaccination in people at risk could also have a protective role [19]. This multidisciplinary management consisting of anti-infective treatment coupled with new therapies [20] could reduce the risk of recurrence and metastases. Moreover, this case seems unique to us due to the unexpected recurrence in this HIV positive field.…”

Successful treatment of a patient with advanced lung adenocarcinoma (EGFR-T790M and C797S cis) with lazertinib: A case report and literature review

“…The suspended cells were then gently washed away with PBS and 3 ml of cell culture medium was added. Photographs were taken at 0h and 24h of scratching, respectively, under a microscope (Olympus, China), and the widths were measured and calculated ( 11 ).…”

Silencing of RhoC induces macrophage M1 polarization to inhibit migration and invasion in colon cancer via regulating the PTEN/FOXO1 pathway

“…Recently, RhoC has been shown to be up‐regulated in various tumours, and may be associated with tumour progress and metastasis. Examples of this are gastric cancer (GC), breast cancer (BC), and oral squamous cell carcinoma (OSCC) 6–8 . For instance, silencing of RhoC suppressed GC cell proliferation, migration and invasion, and resulted in a marked inhibition of GC tumour growth in a xenograft mice model 7 .…”

“…Examples of this are gastric cancer (GC), breast cancer (BC), and oral squamous cell carcinoma (OSCC). [6][7][8] For instance, silencing of RhoC suppressed GC cell proliferation, migration and invasion, and resulted in a marked inhibition of GC tumour growth in a xenograft mice model. 7 Gao et al 8 have reported that decreased RhoC markedly inhibited the invasion and migration abilities of OSCC cells.…”

“…[6][7][8] For instance, silencing of RhoC suppressed GC cell proliferation, migration and invasion, and resulted in a marked inhibition of GC tumour growth in a xenograft mice model. 7 Gao et al 8 have reported that decreased RhoC markedly inhibited the invasion and migration abilities of OSCC cells. In addition, studies have reported that high expression of RhoC correlates with poor prognosis in CC.…”