Silencing RhoA inhibits migration and invasion through Wnt/&amp;beta;-catenin pathway and growth through cell cycle regulation in human tongue cancer

Yan, Gen; Ronghai, Zou; Chen, Zhenggang; Fan, Bing; Wang, Zhaoyan; Wang, Mengying; Yin, Xiaonan; Zhang, Dong; Tong, Lei; Yang, Fang; Jiang, Weina; Fu, Wensheng; Zheng, Jiwei; Bergö, Martin O.; Dalin, Martin G.; Zheng, Jiawei; Chen, Shulan; Zhou, Jianhua

doi:10.1093/abbs/gmu051

Cited by 18 publications

(17 citation statements)

References 50 publications

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“…These results prompted us to look for a further mechanism through which miR-133b inhibits TAp63 expression. RhoA is a founding member of the Rho GTPase family, in which it is most readily recognized for its contributions to cell migration, the organization of the cytoskeleton, cell adhesion, progression through the cell cycle and gene expression [28–31]. It has been verified that miR-133b can bind a site within the 3′ UTR of RhoA to silence the mRNA [21], which we confirmed in a previous study [19].…”

Section: Discussionsupporting

confidence: 78%

Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression

Dai

Zhang

et al. 2016

Oncotarget

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BackgroundTAp63 is known as the most potent transcription activator and tumor suppressor. microRNAs (miRNAs) are increasingly recognized as essential components of the p63 pathway, mediating downstream post-transcriptional gene repression. The aim of present study was to investigate a negative feedback loop between TAp63 and miR-133b.ResultsOverexpression of TAp63 inhibited HCT-116 cell proliferation, apoptosis and invasion via miR-133b. Accordingly, miR-133b inhibited TAp63 expression through RhoA and its downstream pathways. Moreover, we demonstrated that TAp63/miR-133b could inhibit colorectal cancer proliferation and metastasis in vivo and vitro.Materials and MethodsWe evaluated the correlation between TAp63 and miR-133b in HCT-116 cells and investigated the roles of the TAp63/miR-133b feedback loop in cell proliferation, apoptosis and metastasis via MTT, flow cytometry, Transwell, and nude mouse xenograft experiments. The expression of TAp63, miR-133b, RhoA, α-tubulin and Akt was assessed via qRT-PCR, western blot and immunofluorescence analyses. miR-133b target genes were identified through luciferase reporter assays.ConclusionsmiR-133b plays an important role in the anti-tumor effects of TAp63 in colorectal cancer. miR-133b may represent a tiemolecule between TAp63 and RhoA, forming a TAp63/miR-133b/RhoA negative feedback loop, which could significantly inhibit proliferation, apoptosis and metastasis.

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Section: Discussionsupporting

confidence: 78%

Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression

Dai

Zhang

et al. 2016

Oncotarget

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“…In contrast, HCMV infected U373MG-IE1 cells exhibit a higher motility rate, enhancing the defect in the migration caused by the deficiency of each Rho protein. It is worth noting the fact that even in the absence or presence of HCMV, parental and their derivative IE1-knockdown RhoA cells exhibited the lowest motility rate even in this more favorable for the IE1-expressing glioblastoma cells context, providing an additional proof reinforcing the significant role of RhoA to promote cell migration [73,74].…”

Section: Discussionmentioning

confidence: 87%

The Role of RhoA, RhoB and RhoC GTPases in Cell Morphology, Proliferation and Migration in Human Cytomegalovirus (HCMV) Infected Glioblastoma Cells

Tseliou

Al‐Qahtani²,

Alarifi

et al. 2016

Cell Physiol Biochem

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Background/Aims: Rho GTPases are crucial regulators of the actin cytoskeleton, membrane trafficking and cell signaling and their importance in cell migration and invasion is well- established. The human cytomegalovirus (HCMV) is a widespread pathogen responsible for generally asymptomatic and persistent infections in healthy people. Recent evidence indicates that HCMV gene products are expressed in over 90% of malignant type glioblastomas (GBM). In addition, the HCMV Immediate Early-1 protein (IE1) is expressed in >90% of tumors analyzed. Methods: RhoA, RhoB and RhoC were individually depleted in U373MG glioblastoma cells as well as U373MG cells stably expressing the HCMV IE1 protein (named U373MG-IE1 cells) shRNA lentivirus vectors. Cell proliferation assays, migration as well as wound-healing assays were performed in uninfected and HCMV-infected cells. Results: The depletion of RhoA, RhoB and RhoC protein resulted in significant alterations in the morphology of the uninfected cells, which were further enhanced by the cytopathic effect caused by HCMV. Furthermore, in the absence or presence of HCMV, the knockdown of RhoB and RhoC proteins decreased the proliferation rate of the parental and the IE1-expressing glioblastoma cells, whereas the knockdown of RhoA protein in the HCMV infected cell lines restored their proliferation rate. In addition, wound healing assays in U373MG cells revealed that depletion of RhoA, RhoB and RhoC differentially reduced their migration rate, even in the presence or the absence of HCMV. Conclusion: Collectively, these data show for the first time a differential implication of Rho GTPases in morphology, proliferation rate and motility of human glioblastoma cells during HCMV infection, further supporting an oncomodulatory role of HCMV depending on the Rho isoforms' state.

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“…It has been reported that RhoA expression is an independent prognostic factor in gastric cancer, especially diffuse-type gastric cancer [18]. Compared with normal tissues, there is increased RhoA expression in primary tumors and metastatic lymph nodes in squamous cell carcinoma of the tongue (TSCC), where RhoA silencing significantly reduced tumor growth [19]. In nude mice, RhoA silencing suppressed tumor xenograft formation and growth by the induction of tumor cell apoptosis [20].…”

Section: Discussionmentioning

confidence: 99%

“…Zhao et al [21] reported that, in OVCAR3 cells, silencing RhoA, which participates in cancer cell proliferation, metastasis, invasion, and apoptosis, markedly reduced Akt, p70S6k, Bcl-xL, survivin, and vascular endothelial growth factor (VEGF) mRNA and protein expression. Yan et al [19] reported that silencing RhoA in tongue cancer decreased Gal-3, MMP9, β-catenin, and cyclin D1/2 levels while increasing p27Kip1 and p21CIP1/WAF1 levels and suggested that RhoA regulates cancer cell migration and invasion and proliferation through Wnt/β-catenin signaling and cell cycle regulation, respectively, to promote TSCC progression.…”

Section: Discussionmentioning

confidence: 99%

The role of RhoA in vulvar squamous cell carcinoma: a carcinogenesis, progression, and target therapy marker

Wang

Zhang

et al. 2015

Tumor Biol.

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Ras homologue gene family member A (RhoA) is involved in tumor mobility, invasion, and metastasis. We detected RhoA expression in vulvar squamous cell carcinoma (VSCC) tissue, measured RhoA expression in the VSCC cell phenotype, and measured the expression of the relevant molecules after RhoA small interfering RNA (siRNA) transfection in SW962 cells. RhoA has a higher expression level in VSCC than normal vulva skin tissue and was positively associated with the International Federation of Gynecology and Obstetrics (FIGO) stage and differentiation; besides, VSCC patients with lymph node metastasis had higher positive RhoA expression. RhoA messenger RNA and protein expression was significantly reduced in the RhoA siRNA transfectants as compared with the negative control (NC) and mock-transfected cells (p < 0.05). The RhoA siRNA transfectants lead to low growth, G1 arrest, high apoptosis, low migration and invasion (p < 0.05), and suppressed lamellipodia formation as compared to NC and mock-transfected cells. Besides, matrix metalloproteinase-2 (MMP2), MMP9, and cyclinA1 protein expression was downregulated, while that of Bax was upregulated in the RhoA siRNA transfectants (p < 0.05). SW962 cell proliferation rates were significantly lovastatin dose-dependent. Lovastatin caused G1 arrest, high apoptosis, low migration and invasion (p < 0.05), and suppression of lamellipodia formation. Similar to the RhoA siRNA transfectants, lovastatin treatment downregulated RhoA, MMP2, MMP9, and cyclinA1 protein expression, while upregulating that of Bax as compared to that of the NC (p < 0.05). Abnormal RhoA expression in vulvar carcinoma is involved in tumor proliferation and invasion and may be a treatment target. The RhoA inhibitor lovastatin alters VSCC cell migration and proliferation and may be effective for treating VSCC.

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Silencing RhoA inhibits migration and invasion through Wnt/β-catenin pathway and growth through cell cycle regulation in human tongue cancer

Cited by 18 publications

References 50 publications

Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression

Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression

The Role of RhoA, RhoB and RhoC GTPases in Cell Morphology, Proliferation and Migration in Human Cytomegalovirus (HCMV) Infected Glioblastoma Cells

The role of RhoA in vulvar squamous cell carcinoma: a carcinogenesis, progression, and target therapy marker

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