Silencing of Rac3 Inhibits Proliferation and Induces Apoptosis of Human Lung Cancer Cells

Liu, Tieqin; Wang, Gebang; Li, Zhengjun; Tong, Xiangdong; Liu, Hongxu

doi:10.7314/apjcp.2015.16.7.3061

Cited by 18 publications

(14 citation statements)

References 15 publications

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“…RAC3 promoted cell proliferation, migration, and invasion by activating JAK/STAT signaling. Previous studies indicated that RAC3 promoted cell proliferation and cell aggressiveness in several cancers (Chan et al, 2005;Hwang et al, 2005;Engers et al, 2007;Gest et al, 2013;Liu et al, 2015;Zhang et al, 2017). Our results agree with this finding since we demonstrated that RAC3 promoted BCa cell proliferation, migration, and invasion.…”

Section: Discussionsupporting

confidence: 93%

“…RAC3 is shown to be primitively expressed in a wide range of tissues, especially in neuronal tissues, under non-pathological circumstances (Haataja et al, 1997;Corbetta et al, 2009;Vaghi et al, 2014). Recently, research has demonstrated that RAC3 is up-regulated to serve as an oncogene by promoting cell proliferation and cell aggressiveness in several cancers including breast cancer (Chan et al, 2005;Gest et al, 2013), prostate cancer (Engers et al, 2007), brain cancer (Hwang et al, 2005), and lung cancer (Liu et al, 2015;Zhang et al, 2017). According to the bioinformatics analysis results from The Cancer Genome Atlas dataset, RAC3 is highly expressed in BCa tissues when compared with the normal tissues, and as such forecasts a high-risk signature for BCa of clinical relevance (Qiu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer

Chen

Song

et al. 2020

Front. Mol. Biosci.

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Background: Bladder cancer (BCa) represents one of the most common malignant cancers with high incidence and mortality rates globally. Dysregulation of gene expression has been shown to play critical roles in cancer progression. RAC3 is up-regulated to play an oncogenic role in several cancers, however, the underlying mechanism of RAC3 in BCa is yet to be elucidated. Therefore, this study aimed to investigate the function and mechanism of RAC3 in BCa. Methods: Bioinformatics analysis was employed to demonstrate the expression of RAC3 and PYCR1 in BCa tissues, as well as, its correlation with the overall survival rate of BCa patients. RT-qPCR was performed to detect and quantify the mRNA levels of RAC3 and PYCR1 in BCa cells and immortalized human bladder epithelial cells. MTT, colony formation and Transwell assays were employed to determine cell proliferation, migration, and invasion. Western blotting was performed to detect and quantity proteins expressed. Results: Bioinformatics analysis showed that RAC3 was up-regulated in BCa tissues when compared to normal tissues. Patients with up-regulated RAC3 expression had lower overall survival than patients with down-regulated RAC3 expression. The mRNA level of RAC3 was higher in BCa cells than in immortalized human bladder epithelial cell. RAC3 promoted cell proliferation, migration, and invasion by activating Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) signaling. Notably, RAC3 up-regulated PYCR1, which is positively correlated with RAC3, and thus played an oncogenic role in BCa cells. Moreover, we demonstrated that RAC3 overexpression activated JAK/STAT signaling via PYCR1 axis. Conclusion: RAC3 promoted cell proliferation, migration, and invasion. This is likely due to its role in activating JAK/STAT signaling, which was mediated by PYCR1. This study provides a novel biomarker and target for diagnostic or therapeutic intervention for BCa.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer

Chen

Song

et al. 2020

Front. Mol. Biosci.

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“…Regarding the hypomethylated candidate genes, overexpression of BST2 is associated with poor survival in patients with CRC as well as those with esophageal or gastric cancer [ 33 ]. Additionally, the silencing of RAC3 inhibits proliferation and induces apoptosis in human lung cancer cells [ 34 ]. Accordingly, the three hypermethylated ( EGF , CHST10 , EPDR1 ) and two hypomethylated ( BST2 , RAC3 ) candidate genes were further validated by Q-MSP using 75 pairs of CRC and adjacent normal tissues.…”

Section: Resultsmentioning

confidence: 99%

Prognostic Values of EPDR1 Hypermethylation and Its Inhibitory Function on Tumor Invasion in Colorectal Cancer

Chu

Chang

Wang

et al. 2018

Cancers

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Aberrant DNA methylation is a potential mechanism underlying the development of colorectal cancer (CRC). Thus, identification of prognostic DNA methylation markers and understanding the related molecular functions may offer a new perspective on CRC pathogenesis. To that end, we explored DNA methylation profile changes in CRC subtypes based on the microsatellite instability (MSI) status through genome-wide DNA methylation profiling analysis. Of 34 altered genes, three hypermethylated (epidermal growth factor, EGF; carbohydrate sulfotransferase 10, CHST10; ependymin related 1, EPDR1) and two hypomethylated (bone marrow stromal antigen 2, BST2; Rac family small GTPase 3, RAC3) candidates were further validated in CRC patients. Based on quantitative methylation-specific polymerase chain reaction (Q-MSP), EGF, CHST10 and EPDR1 showed higher hypermethylated levels in CRC tissues than those in adjacent normal tissues, whereas BST2 showed hypomethylation in CRC tissues relative to adjacent normal tissues. Additionally, among 75 CRC patients, hypermethylation of CHST10 and EPDR1 was significantly correlated with the MSI status and a better prognosis. Moreover, EPDR1 hypermethylation was significantly correlated with node negativity and a lower tumor stage as well as with mutations in B-Raf proto-oncogene serine/threonine kinase (BRAF) and human transforming growth factor beta receptor 2 (TGFβR2). Conversely, a negative correlation between the mRNA expression and methylation levels of EPDR1 in CRC tissues and cell lines was observed, revealing that DNA methylation has a crucial function in modulating EPDR1 expression in CRC cells. EPDR1 knockdown by a transient small interfering RNA significantly suppressed invasion by CRC cells, suggesting that decreased EPDR1 levels may attenuate CRC cell invasion. These results suggest that DNA methylation-mediated EPDR1 epigenetic silencing may play an important role in preventing CRC progression.

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“…In our previous studies, we proved that Rac3 could promote cell proliferation and inhibit apoptosis in lung adenocarcinoma cell lines 15 , 16 . However, the role of Rac3 in lung adenocarcinoma cells invasion and migration is not clear.…”

Section: Introductionmentioning

confidence: 91%

Rac3 Regulates Cell Invasion, Migration and EMT in Lung Adenocarcinoma through p38 MAPK Pathway

Zhang¹,

Liu²,

Wang³

et al. 2017

J. Cancer

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Background: The role of Rac3 in cell proliferation in lung adenocarcinoma has been tackled in our previous study. However, the role of Rac3 in cell invasion and migration of lung adenocarcinoma is still not clear.Methods: The expression of Rac3 in lung adenocarcinoma specimens and paired noncancerous normal tissues were evaluated by immunohistochemistry. Lentivirus-mediated RNA interference (RNAi) was employed to silence Rac3 in lung adenocarcinoma cell lines A549 and H1299. A p38 MAPK inhibitor (LY2228820) was employed to inhibit activity of p38 MAPK pathway. Cell invasion and migration in vitro were examined by invasion and migration assays, respectively. PathScan® intracellular signaling array kit and western blot were employed in mechanism investigation.Results: Rac3 expression was frequently higher in lung adenocarcinoma than paired noncancerous normal tissues. Rac3 expression was an independent risk factor for lymphonode metastasis, and was associated with worse survival outcome. Silencing of Rac3 inhibited cell invasion and cell migration in lung adenocarcinoma cell lines. Knockdown of Rac3 decreased activity of p38 MAPK pathway. LY2228820, which was an important p38 MAPK inhibitor, inhibited Rac3-induced cell invasion and migration of lung adenocarcinoma. E-cadherin expression was increased and vimentin expression was decreased after silencing of Rac3 or following the treatment of LY2228820.Conclusions: Our findings suggest that Rac3 regulates cell invasion, migration and EMT via p38 MAPK pathway. Rac3 may be a potential biomarker of invasion and metastasis for lung adenocarcinoma, and knockdown of Rac3 may potentially serve as a promising therapeutic target for lung adenocarcinoma.

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Silencing of Rac3 Inhibits Proliferation and Induces Apoptosis of Human Lung Cancer Cells

Cited by 18 publications

References 15 publications

RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer

RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer

Prognostic Values of EPDR1 Hypermethylation and Its Inhibitory Function on Tumor Invasion in Colorectal Cancer

Rac3 Regulates Cell Invasion, Migration and EMT in Lung Adenocarcinoma through p38 MAPK Pathway

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