Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer

Lee, Hyun Hee; Son, Young Joon; Lee, Won Hyeok; Park, Young Woo; Chae, Seoung Wan; Cho, Wha Ja; Kim, Young Min; Choi, Hye-Jeong; Choi, Dong Lak; Jung, Seok Won; Min, Young Joo; Park, Soon Eun; Lee, Byung Ju; Jeong, Hee; Park, Jeong Woo

doi:10.1002/ijc.24847

Cited by 74 publications

(102 citation statements)

References 40 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cell Lines-Previously, we prepared Colo320/TTP, a stable transfectant derivative of Colo320 that overexpresses TTP, and reported that VEGF expression was reduced by overexpression of TTP (32). While we were searching for genes with expression levels changed by TTP overexpression, we found that the LATS2 expression level was also reduced in Colo320/TTP cells compared with that in Colo320 cells (Fig.…”

Section: Lats2 Expression Is Inversely Correlated With Ttp Expressionmentioning

confidence: 93%

“…Colo320/pcDNA and Colo320/TTP cells, stably transfected with pcDNA4.1 and pcDNA-TTP, respectively, were prepared as described previously (32). A549, Colo320, Colo320/pcDNA, and Colo320/TTP cells were cultured in RPMI 1640 medium, and 293-EBNA, NT2, HepG2, and PA1 cells were cultured in Dulbecco's modified Eagle's medium.…”

Section: Methodsmentioning

confidence: 99%

“…Plasmids, Small Interfering RNAs (siRNAs), Transfections, and Dual-Luciferase Assay-The pcDNA-TTP construct has been described previously (32). pcDNA6/V5-TTP was prepared by subcloning EcoRI/XhoI-digested fragments from pcDNA-TTP into pcDNA6/V5-HisA (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Stability of the LATS2 Tumor Suppressor Gene Is Regulated by Tristetraprolin

Lee

Kim

et al. 2010

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

LATS2 is a tumor suppressor gene implicated in the control of cell growth and the cell cycle. Here, we investigated the posttranscriptional regulation of LATS2 expression by tristetraprolin (TTP). Our results show that the expression level of LATS2 is inversely correlated with TTP expression in human cancer cell lines. Overexpression of TTP reduced the expression level of LATS2. Conversely, treatment with small interfering RNA against TTP increased the expression level of LATS2 through stabilization of LATS2 mRNA and suppressed the proliferation of A549 human lung cancer cells. LATS2 mRNA contains AUrich elements (AREs) within the 3-untranslated region, and TTP destabilized a luciferase mRNA containing LATS2 ARE. In addition, RNA electrophoretic mobility shift assay revealed that TTP directly bound to the ARE of LATS2 mRNA. These results establish LATS2 mRNA as a physiological target of TTP and suggest the possibility that TTP controls cell growth through regulation of LATS2 mRNA stability.LATS2 is a new member of the LATS tumor suppressor family (1-3). The LATS2 gene is located at chromosome 13q11-12 and encodes a 1046-amino acid protein that contains a C-terminal serine/threonine kinase domain (4). According to recent publications, LATS2 appears to coordinate the cell cycle, cell proliferation, and cell death. LATS2 promotes the stabilization of p53 by inactivating MDM2 (5), plays a role in maintenance of mitotic fidelity (6), and regulates spindle organization through recruitment of ␥-tubulin to the centrosome (7). Overexpression of LATS2 results in G 2 /M arrest via inhibition of Cdc2 kinase activity (8), inhibition of G 1 /S transition via down-regulation of cyclin E/Cdk2 kinase activity (9), and induction of apoptosis via down-regulation of apoptotic inhibitors such as Bcl-2 and Bcl-x L (10). Deletion of LATS2 in flies (11, 12) and mice (13) accelerates cell proliferation and tumor development, indicating that the reduced function of the LATS2 gene leads to accelerated cell proliferation.Expression of LATS2 is down-regulated in several human cancer cells (14 -18). The mechanisms for down-regulation have been the subject of substantial interest. It has been reported that the expression of LATS2 in breast cancer (14), astrocytoma (17), and acute lymphoblastic leukemia (18, 19) is down-regulated by hypermethylation of the promoter. In addition, LATS2 mRNA is down-regulated at the post-transcriptional level by microRNA-372 and microRNA-373 in testicular germ cell tumors (20), gastric cancer cells (21), and esophageal cancer cells (22), suggesting that the expression of the LATS2 gene is controlled at the post-transcriptional level as well as the transcriptional level.Post-transcriptional regulation of gene expression is also mediated by AU-rich elements (AREs) 4 located in the 3Ј-untranslated region (3Ј-UTR) of a variety of short-lived mRNAs such as cytokines and proto-oncogenes (23). The destabilizing function of AREs is believed to be regulated by ARE-binding proteins (24). Numerous ARE-binding proteins ha...

show abstract

Section: Lats2 Expression Is Inversely Correlated With Ttp Expressionmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Stability of the LATS2 Tumor Suppressor Gene Is Regulated by Tristetraprolin

Lee

Kim

et al. 2010

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…TTP expression is significantly decreased in various cancers (Brennan et al, 2009), and this down-regulation correlates with increased expression of proto-oncogenes (Lee et al, 2010a;Young et al, 2009). The low level of TTP in cancer cells may not be sufficient to inhibit IL-23 expression, resulting in high IL-23 levels in cancer cells (Kesselring et al, 2010;Langowski et al, 2006;Martin-Orozco et al, 2009) which in turn may support tumor development.…”

Section: Discussionmentioning

confidence: 99%

“…The AREs may destabilize inflammatory signaling mRNAs through specific binding of proteins that promote mRNA degradation (Caput et al, 1986;Shyu and Wilkinson 2000). Tristetraprolin (TTP) is a well-characterized ARE-binding protein that is involved in posttranscriptional regulation of inflammatory cytokines, proto-oncogenes, and growth regulatory genes (Cha et al, 2011;Lee et al, 2010a;2012;2013). TTP-knockout mice develop severe inflammatory arthritis and autoimmune dysfunction, indicating a role of TTP in limiting the inflammatory response (Taylor et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Tristetraprolin Down-Regulates IL-23 Expression in Colon Cancer Cells

Lee

Song

et al. 2013

Molecules and Cells

Self Cite

View full text Add to dashboard Cite

mRNA 3'UTR demonstrated that the ARE cluster between the third and fifth AREs was responsible for TTP-mediated destabilization of IL-23 mRNA. A RNA electrophoretic mobility shift assay confirmed that TTP binds to this ARE cluster. Taken together, these results demonstrate that TTP acts as a negative regulator of IL-23 gene expression in mouse colon cancer cells and suggest its potential application as a novel therapeutic target to control IL-23-mediated tumor promotion.

show abstract

Tumor suppressing effects of tristetraprolin and its small double‐stranded RNAs in bladder cancer

et al. 2020

View full text Add to dashboard Cite

Bladder cancer (BCa) is a common malignant tumor of urinary system with few treatments, so more useful therapeutic targets are still needed. Antitumor effects of tristetraprolin (TTP) have been explored in many type tumors, but its roles in bladder cancer are still unknown until now. In this study, public expression profiles and tissue microarray analysis showed that TTP mRNA and protein levels decreased in BCa relative to the normal bladder tissue. To explore biological functions of TTP in BCa, 488 TTP target genes, which could be both suppressed and bound by TTP, were identified by comprehensively analyzing publicly available high‐throughput data obtained from Gene Expression Omnibus (GEO). Gene enrichment analysis showed that these genes were enriched in pathways such as cell cycle, epithelial to mesenchymal transition (EMT), and Wnt signaling. Clustering analysis and gene set variation analysis indicated that patients with high expression of TTP target genes had poorer prognosis and stronger tumor proliferation ability relative to the BCa patients with low expression of TTP target genes. In vitro experiments validated that TTP could suppress proliferation, migration, and invasiveness of BCa cells. And TTP could suppress mRNA expression of cyclin‐dependent kinase 1 (CDK1) in BCa cells by target its 3′ UTR. Then, we identified a new small double‐stranded RNA (dsRNA) named dsTTP‐973 which could increase TTP expression in BCa cells, in vivo and in vitro experiments revealed that dsTTP‐973 could suppress aggressiveness of BCa. In conclusion, TTP played a role of tumor suppressor gene in BCa like other tumors, and its dsRNA named dsTTP‐973 could induce TTP expression in BCa and suppress aggressiveness of BCa. With the help of materials science, dsTTP‐973 may become a potential treatment for BCa in the future.

show abstract

Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer

Cited by 74 publications

References 40 publications

Stability of the LATS2 Tumor Suppressor Gene Is Regulated by Tristetraprolin

Stability of the LATS2 Tumor Suppressor Gene Is Regulated by Tristetraprolin

Tristetraprolin Down-Regulates IL-23 Expression in Colon Cancer Cells

Tumor suppressing effects of tristetraprolin and its small double‐stranded RNAs in bladder cancer

Contact Info

Product

Resources

About