Overexpression of RhoA is associated with poor prognosis in hepatocellular carcinoma

Li, X.R.; Ji, Feiyang; Ouyang, Jun; Wu, Wen‐Hsin; Qian, Leimin; Yang, Kun

doi:10.1016/j.ejso.2006.05.012

Cited by 56 publications

(52 citation statements)

References 16 publications

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“…Numerous studies indicate that deregulated signaling of Rho GTPases plays an important role in HCC progression and metastasis (9). RhoA pathway associates with venous invasion, cell differentiation and poor prognosis (22), correlating with tumor progression and metastasis (23)(24)(25). Rac1 GTPase is crucial for actin cytoskeleton reorganization at the cell cortex and is involved in processes of HCC migration and invasion (26)(27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

Loss of ARHGDIA expression is associated with poor prognosis in HCC and promotes invasion and metastasis of HCC cells

Liang

Huang

et al. 2014

International Journal of Oncology

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Abstract. Rho GTPases control a wide range of cellu lar processes and contribute to tumor invasion and metastasis. As a regulator of Rho activity, ARHGDIA is aberrantly expressed in several types of tumors and plays different roles in the tumor process. To elucidate the role of ARHGDIA in HCC, we investigated the patterns of its expression, prognosis and clinical profiles in HCC. Functional assays were performed to investigate whether the alteration of ARHGDIA has an effect on cell growth, migration and invasion, as well as the status of Rho GTPases. We found that ARHGDIA was frequently downregulated in HCC and associated with tumor invasion and metastasis. Moreover, ARHGDIA was significantly associated with OS and TTR of HCC patients. Low level of ARHGDIA exhibited a decreased postoperative OS and a shorter TTR compared those with high levels. Functional assays showed that loss of ARHGDIA promoted HCC cell migration and invasion in vitro and lung metastasis formation in vivo. We found that loss of ARHGDIA significantly induced Rac1 and RhoA activation which may contribute to invasion and metastasis of HCC. In conclusion, the present study has identified loss of ARHGDIA contributed to the processes of hepatic tumorigenesis, in particular invasion and metastasis which may provide a potential therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 99%

Loss of ARHGDIA expression is associated with poor prognosis in HCC and promotes invasion and metastasis of HCC cells

Liang

Huang

et al. 2014

International Journal of Oncology

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“…As a member of the Rho GTPase family, RhoA is an important factor in promoting the uncontrolled proliferation as well as the invasive and metastatic properties of cancer cells [24]. Accordingly, the clinicopathological correlation of RhoA levels with HCC has been widely evaluated, and it was found that a high RhoA protein expression is detectable in both idiopathic and early-stage recurrent HCC [9], and high expression is also closely related to venous invasion, differentiation [11], tumor progression, and the metastasis of hepatocarcinoma cells [25,26]. Moreover, proteomic analysis also identified RhoA as one of the most significantly up-regulated proteins in HCC [27].…”

Section: Discussionmentioning

confidence: 99%

“…Activating the RhoA/Rho pathway increases tumor cell migratory properties, such as invadopodia, amoeboid migration, and plasticity abilities [10]. Additionally, the expression level of RhoA is directly correlated to the clinicopathologic outcome, as the overexpression of RhoA has been shown to be directly correlated to a poor prognosis of HCC [11]. Furthermore, X.L.…”

mentioning

confidence: 99%

Inhibition of RhoA expression by adenovirus-mediated siRNA combined with TNF-α induced apoptosis of hepatocarcinoma cells

Yin

Zhao

Huang

et al. 2015

BME

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Abstract. Tumor necrosis factor-alpha (TNF-α) has been used as an effective treatment for Hepatocellular Carcinoma, however, inducing tumor cell apoptosis by TNF-α alone is still unsatisfactory. RhoA is highly expressed in hepatocarcinoma cells and can be activated by TNF-α. The activation of RhoA directly leads to a poor prognosis of HCC. Therefore, we propose to investigate the therapeutic effect of TNF-α together with RhoA siRNA. RhoA inhibition was accomplished by constructing a recombinant adenovirus that can efficiently express RhoA siRNA in HepG2 cells. The recombinant adenovirus AdshRNA-RhoA and AdU6-control were generated by adenovirus-mediated siRNA expression system. The inhibition effects were detected by RT-PCR in addition to immunoblot to quantify the decreased levels of RhoA expression, and the therapeutic effect for HCC was demonstrated by the proliferation and apoptosis ratios of HepG2 cells. The inhibition effects of RhoA by AdshRNA-RhoA were significant at both mRNA and protein levels: the transcription of RhoA mRNA decreased by 74.46%, and the expression of protein decreased by 76.48%. The proliferation rate of HepG2 cells detected by MTT showed that a treatment of AdshRNA-RhoA and TNF-α together could strengthen the suppression ability of TNF-α to HepG2 cells, resulting in approximately 14.2% more than those treated with only TNF-α. FCA and TUNEL assays results revealed that the combined treatment can induce apoptosis in approximately 52.14%-65% of the HepG2 cells, whereas this ratio in the TNF-α-alone group was only 21.91%-32%. Our results showed that AdshRNA-RhoA can efficiently enhance the TNF-α-induced apoptosis of hepatocarcinoma cells. This method might be a useful therapeutic route in HCC and other tumors.

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“…The high expression of RhoA protein in HCC plays an important role in intrahepatic recurrence of patients who underwent a hepatectomy for HCC, and RhoA is a useful marker for predicting early recurrence in an early-stage HCC (Fukui et al, 2006). Overexpression of RhoA is associated with poor prognosis in HCC (Li et al, 2006;Hu et al, 2013).…”

Section: Hepatocellular Carcinoma (Hcc)mentioning

confidence: 99%

RHOA (ras homolog gene family, member A)

Manso¹

2017

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Overexpression of RhoA is associated with poor prognosis in hepatocellular carcinoma

Cited by 56 publications

References 16 publications

Loss of ARHGDIA expression is associated with poor prognosis in HCC and promotes invasion and metastasis of HCC cells

Loss of ARHGDIA expression is associated with poor prognosis in HCC and promotes invasion and metastasis of HCC cells

Inhibition of RhoA expression by adenovirus-mediated siRNA combined with TNF-α induced apoptosis of hepatocarcinoma cells

RHOA (ras homolog gene family, member A)

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