RNA‐interference‐mediated Cdc42 silencing down‐regulates phosphorylation of STAT3 and suppresses growth in human bladder‐cancer cells

Wu, Fu-guo; Chen, Yirong; Li, Yuan; Ju, Jun; Wang, Zhiping; Yan, Dongwen

doi:10.1042/ba20070107

Cited by 15 publications

(14 citation statements)

References 40 publications

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“…In contrast, downregulation of Cdc42 signals can inhibit anchorage-independent growth and induce apoptosis via the PI(3)K-Akt and Erk signaling cascades and the p53 tumor suppressor (8). Consistent with these reports, Cdc42 silencing by small hairpin RNA was able to reverse the metastatic and growth behavior of human colorectal cancer cells and bladder cancer cells (9,10). Taken together, the observed effects of Cdc42 over-expression and silencing on the cell malignant transformation indicate a role for Cdc42 in regulating tumor metastasis and progression.…”

Section: Introductionsupporting

confidence: 77%

Expression analysis of Cdc42 in lung cancer and modulation of its expression by curcumin in lung cancer cell lines

Chen

Jiao²,

Qinghua³

et al. 2012

Int J Oncol

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Abstract. Cdc42, a Rho GTPase family member, is involved in cell transformation, proliferation, survival, invasion and metastasis of human cancer cells. Overexpression of Cdc42 has been reported in several types of human cancer. However, the underlying mechanisms are not well understood. The present study showed that Cdc42 was overexpressed in 80 of 110 primary lung cancer patients, and overexpression of Cdc42 was significantly associated with high TNM stage and lymph node metastasis. Moreover, RNAi-mediated suppression of Cdc42 expression reduced actin filopodia formation, migration and invasion potential of a highly metastatic lung cancer cell line, 801D. In parallel, 801D cells were treated with curcumin and the effect on the expression of the Cdc42 gene at the transcriptional and translational levels was analyzed by RT-PCR and Western blotting. Curcumin inhibited cell migration, invasion and downregulated Cdc42 gene and Cdc42-related target gene expression in 801D cells. It also induced rearrangements of the actin cytoskeleton. These effects mimicked those of Cdc42 knockdown. Furthermore, xenograft experiments confirmed the suppression of tumor growth and invasion in vivo, which was due to the effect of curcumin and the inhibition of Cdc42 by curcumin. Our results showing the downregulation of Cdc42 expression by curcumin in lung cancer cells taken together with the clinical data suggest a potential therapeutic role for curcumin in inducing Cdc42-mediated inhibition of invasion of lung cancer cells.

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Section: Introductionsupporting

confidence: 77%

Expression analysis of Cdc42 in lung cancer and modulation of its expression by curcumin in lung cancer cell lines

Chen

Jiao²,

Qinghua³

et al. 2012

Int J Oncol

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“…In a study by Zins et al (21) it was demonstrated that a Ras-related C3 botulinum toxin substrate 1/Cdc42 GTPase-specific small molecule inhibitor could effectively suppress the growth of primary human prostate cancer xenografts and prolong survival in mice. Furthermore, it has been reported that Cdc42 expression is significantly upregulated in bladder cancer tissues compared with that in normal tissues, and Cdc42 silencing caused by siRNA can inhibit the phosphorylation of STAT3 and suppress the growth of bladder cancer cells, suggesting that Cdc42 may serve as a therapeutic target for the treatment of bladder cancer (22,14). In the present study, it was demonstrated that miR-195 upregulation could inhibit Cdc42 protein expression in bladder cancer T24 cells.…”

supporting

confidence: 48%

“…As Cdc42/STAT3 signaling has been found to largely contribute to bladder cancer cell proliferation (14), and miR-195 can inhibit the protein expression of Cdc42 in bladder cancer T24 cells, we speculated that miR-195 could play a suppressive role in bladder cancer cell proliferation, via downregulation of Cdc42/STAT3 signaling. To verify this theory, bladder cancer T24 cells were transfected with miR-195 mimics or Cdc42-specific siRNA, or co-transfected with miR-195 mimics and Cdc42 plasmid, respectively.…”

Section: Cdc42/stat3 Signaling Is Involved In the Mir-195-mediated Inmentioning

confidence: 99%

microRNA-195 inhibits cell proliferation in bladder cancer via inhibition of cell division control protein 42 homolog/signal transducer and activator of transcription-3 signaling

Zhao¹,

Lin²,

Chen³

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. microRNA (miR)-195 acts as a suppressor in multiple types of malignant tumors, including bladder cancer; however, the detailed function of miR-195 in bladder cancer remains largely unknown. The aim of the present study was to investigate the role of miR-195 in the regulation of bladder cancer cell proliferation and to determine whether cell division control protein 42 homolog (Cdc42)/signal transducer and activator of transcription-3 (STAT3) signaling acts as a downstream effector of miR-195 in bladder cancer cells. Reverse transcription-quantitative polymerase chain reaction was used to determine the expression levels of miR-195 in bladder cancer tissues and normal adjacent tissue. The results revealed that the expression of miR-195 was significantly downregulated in bladder cancer tissues compared with that in the normal adjacent tissues. A luciferase reporter assay was then conducted, which identified Cdc42 as a direct target of miR-195, and the expression of Cdc42 was significantly upregulated in bladder cancer tissues, as determined by western blotting. Furthermore, miR-195 negatively regulated the protein expression of Cdc42 in bladder cancer cells. An MTT assay was also conducted to determine the rate of cell proliferation. Upregulation of miR-195 or the inhibition of Cdc42 could inhibit bladder cancer cell proliferation, possibly through activation of STAT3 signaling. In addition, restoration of Cdc42 could reverse the inhibitory effect of miR-195 upregulation on bladder cancer cell proliferation. In conclusion, the results of the present study suggest that miR-195 plays an inhibitory role in the regulation of bladder cancer cell proliferation by directly targeting Cdc42/STAT3 signaling.

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“…5B). Notably, silencing of CDC42 is lethal in Candida (39) and inhibits the growth of mammalian cells (70). More importantly, Cdc42p (cell division cycle 42) is involved in C. albicans filament-specific characteristics, including hyphal growth and filament-specific gene transcripts (12,68,73).…”

Section: Discussionmentioning

confidence: 99%

Killing of Candida albicans Filaments by Salmonella enterica Serovar Typhimurium Is Mediated by sopB Effectors, Parts of a Type III Secretion System

Kim

Mylonakis

2011

Eukaryot Cell

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Although bacterial-fungal interactions shape microbial virulence during polymicrobial infections, only a limited number of studies have evaluated this interaction on a genetic level. We report here that one interaction is mediated by sopB, an effector of a type III secretion system (TTSS) of Salmonella enterica serovar Typhimurium. In these studies, we screened 10 TTSS effector-related mutants and determined their role in the killing of C. albicans filaments in vitro during coinfection in planktonic environments. We found that deleting the sopB gene (which encodes inositol phosphatase) was associated with a significant decrease in C. albicans killing at 25°C after 5 days, similar to that caused by the deletion of sipB (which encodes TTSS translocation machinery components). The sopB deletion dramatically influenced the killing of C. albicans filaments. It was associated with repressed filamentation in the Caenorhabditis elegans model of C. albicans-S. Typhimurium coinfection, as well as with biofilm formation by C. albicans. We confirmed that SopB translocated to fungal filaments through SipB during coinfection. Using quantitative real-time PCR assays, we found that the Candida supernatant upregulated the S. Typhimurium genes associated with C. albicans killing (sopB and sipB). Interestingly, the sopB effector negatively regulated the transcription of CDC42, which is involved in fungal viability. Taken together, these results indicate that specific TTSS effectors, including SopB, play a critical role in bacterialfungal interactions and are important to S. Typhimurium in order to selectively compete with fungal pathogens. These findings highlight a new role for TTSS of S. Typhimurium in the intestinal tract and may further explain the evolution and maintenance of these traits.Microbial survival is based on diverse bacterial-bacterial, fungal-fungal, and bacterial-fungal interactions. These interactions are ubiquitous in nature, as well as in clinical environments, but very little is known about the genetic mechanism(s) associated with these interactions (51). Most of the previous studies have focused on Candida albicans, the opportunistic fungal pathogen that can exist as both yeast and filamentous cells according to its growing circumstances and conditions (59). C. albicans is the most common pathogenic fungus and may cause mucosal and systemic infections in immunosuppressed and immunocompetent hosts. The morphological transition from a yeast to a filamentous cell is critical for C. albicans pathogenesis (34, 55). Interestingly, the ability of C. albicans to develop filaments is also impacted by the presence of bacterial pathogens (8), and this association was extensively described during the interaction between C. albicans and various pathogenic bacteria, including Streptococcus gordonii (5), Staphylococcus epidermidis (2), Pseudomonas aeruginosa (25), Burkholderia cenocepacia (8), and Acinetobacter baumannii (52). However, limited work has been done on the interaction of C. albicans with intestinal bacterial p...

show abstract

RNA‐interference‐mediated Cdc42 silencing down‐regulates phosphorylation of STAT3 and suppresses growth in human bladder‐cancer cells

Cited by 15 publications

References 40 publications

Expression analysis of Cdc42 in lung cancer and modulation of its expression by curcumin in lung cancer cell lines

Expression analysis of Cdc42 in lung cancer and modulation of its expression by curcumin in lung cancer cell lines

microRNA-195 inhibits cell proliferation in bladder cancer via inhibition of cell division control protein 42 homolog/signal transducer and activator of transcription-3 signaling

Killing of Candida albicans Filaments by Salmonella enterica Serovar Typhimurium Is Mediated by sopB Effectors, Parts of a Type III Secretion System

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