Inhibition of DLC-1 gene expression by RNA interference in the colon cancer LoVo cell line

Jin, Yueling; Tian, Xiaoqiang; Shang, Yue; Huang, Peiling

doi:10.3892/or.19.3.669

Cited by 14 publications

(15 citation statements)

References 30 publications

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“…Overall, ectopic expression of DLC1 suppresses breast, liver, and kidney cancer cell migration (6-8). Meanwhile, silencing of endogenous DLC1 in breast and colon cancer cells promotes migration (9-10). The regulatory mechanism of DLC1 in cell migration as well as other cellular events has been linked to its negative regulation of the RhoA pathway through the GAP domain.…”

Section: Introductionmentioning

confidence: 99%

Silencing of DLC1 Upregulates PAI-1 Expression and Reduces Migration in Normal Prostate Cells

Shih

Takada

2012

Molecular Cancer Research

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Deleted in liver cancer 1 (DLC1) is a GTPase activating protein (GAP) domain containing tumor suppressor that localizes to focal adhesions. In cancer cells, loss of DLC1 is known to enhance cancer cell migration. However, the role of DLC1 in normal cell migration has not been well studied. Here, we show that silencing of DLC1 (shDLC1) in normal prostate epithelial cells reduces cell migration in both transwell and wound healing assays. This migration defect is mainly due to upregulation of plasminogen activator inhibitor 1 (PAI-1). Silencing of PAI-1 rescues the shDLC1 reduced migration phenotype. Re-expression of DLC1 suppresses PAI-1 and restores the migration defect as well. In contrast, DLC1-K714E (GAP inactive) mutant neither decreases the PAI-1 level nor rescues the shDLC1 migration defect. Interestingly, DLC1-Y442F (tensin-binding and focal adhesion-localizing defective) mutant is able to suppress PAI-1 expression but does not restore the migration defect. Furthermore, PAI-1 upregulation in shDLC1 cells is EGFR-MEK pathway dependent and is able to promote in vitro angiogenesis. Together, our results demonstrate that at least two new mechanisms are involved in DLC1-mediated normal cell migration. (I) DLC1 modulates the expression of PAI-1, which is a negative regulator for cell migration, in a GAP domain and EGFR-MEK dependent manner. (II) Independent of PAI-1, the interaction of DLC1 with tensin members positively regulates cell migration.

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Section: Introductionmentioning

confidence: 99%

Silencing of DLC1 Upregulates PAI-1 Expression and Reduces Migration in Normal Prostate Cells

Shih

Takada

2012

Molecular Cancer Research

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“…Our previous study has showed that restoration of DLC1 expression in colon cancer HT29 cells significantly inhibited cell proliferation and migration, induced apoptosis and cell cycle arrest [6]. In contrast, inhibition of DLC1 gene expression by RNA interference in LoVo cell line caused adverse effects [7].…”

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confidence: 99%

MicroRNA-141 regulates the tumour suppressor DLC1 in colorectal cancer

Wu¹,

Zhu²,

Sun³

et al. 2015

neo

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Our previous study has showed that DLC1 acts as a functional tumor suppressor in colorectal cancer (CRC) cell lines. The aims of this study were to determine whether DLC1 is a target of MicroRNA (miRNA) regulation and to evaluate the role of this mechanism in CRC. By bioinformatics approach and literature, miR-141 was chosen for further study. The miR-141 mimic, miR-141 inhibitor were synthesized and transfected to Lovo cells. Cell growth was determined by MTT and in vivo models. The flow cytometric analysis for cell cycle determination and transwell assays for evaluating the cell invasion were used. Luciferase reporter assays and Western blots showed that DLC1 was a direct target of miR-141 in CRC. The expression levels of miR-141 were obviously up-regulated in CRC tissues compared to non-cancerous tissues, while DLC1 expression levels were down-regulated in a high proportion of clinical samples (14/18). In addition, correlation analyses revealed negative correlation between miR-141 levels and DLC1 expression levels in CRC tissues. MiR-141 overexpression promoted cell growth in vitro and in vivo, promoted cell cycle progression and invasion in Lovo cells. Furthermore, re-introduction of DLC1 in miR-141-overexpressing Lovo cells decreased growth rate of cells, increase of the percentage in G0/G1 phase and decreased the number of migrating cells. In conclusion, we demonstrated that miR-141 is up-regulated in CRC and acts as a functional oncogene by targeting DLC1.

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“…Reexpression of DLC-1 gene in DLC-1 null cells inhibits tumor cell growth and metastasis (Goodison et al, 2005;Kim et al, 2007). Inhibition of DLC-1 expression using RNA interference promoted cell proliferation and migration of in the colon cancer cell line (Jin et al, 2008) and hepatocellular carcinoma in mice (Xue et al, 2008). These results imply that DLC-1 acts as tumor suppressor gene and may be a candidate therapeutic target for cancer.…”

Section: Discussionmentioning

confidence: 75%

Transcriptional induction of DLC-1 gene through Sp1 sites by histone deacetylase inhibitors in gastric cancer cells

Kim

Jong

et al. 2008

Exp Mol Med

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We previously reported that trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, induced DLC-1 mRNA expression and accumulated acetylated histones H3 and H4 associated with the DLC-1 promoter in DLC-1 non-expressing gastric cancer cells. In this study, we demonstrated the molecular mechanisms by which TSA induced the DLC-1 gene expression. Treatment of the gastric cancer cells with TSA activates the DLC-1 promoter activity through Sp1 sites located at -219 and -174 relative to the transcription start site. Electrophoretic mobility-shift assay (EMSA) revealed that Sp1 and Sp3 specifically interact with these Sp1 sites and showed that TSA did not change their binding activities. The ectopic expression of Sp1, but not Sp3, enhances the DLC-1 promoter responsiveness by TSA. Furthermore, the TSA-induced DLC-1 promoter activity was increased by p300 expression and reduced by knockdown of p300. These results demonstrated the requirement of specific Sp1 sites and dependence of Sp1 and p300 for TSA-mediated activation of DLC-1 promoter.

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Inhibition of DLC-1 gene expression by RNA interference in the colon cancer LoVo cell line

Cited by 14 publications

References 30 publications

Silencing of DLC1 Upregulates PAI-1 Expression and Reduces Migration in Normal Prostate Cells

Silencing of DLC1 Upregulates PAI-1 Expression and Reduces Migration in Normal Prostate Cells

MicroRNA-141 regulates the tumour suppressor DLC1 in colorectal cancer

Transcriptional induction of DLC-1 gene through Sp1 sites by histone deacetylase inhibitors in gastric cancer cells

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