Decreased Level of PDCD4 (Programmed Cell Death 4) Protein Activated Cell Proliferation in the Lung of A/J Mouse

Hwang, Sung‐Joo; Minai-Tehrani, Arash; Lim, Hyung-Taek; Shin, Ji‐Young; An, Gil-Hwan; Lee, Kee-Ho; Park, Keerang; Kim, Yeonsoo; Beck, George R.; Yang, Huiling; Cho, Myung‐Haing

doi:10.1089/jamp.2009.0778

Cited by 10 publications

(8 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An inverse correlation of PDCD4 and p-Akt expression has been reported in colorectal cancer tissue samples [33] . shRNA PDCD4 activated Akt pathway, leading to the increased expressions of p-Akt, mTOR and p70S6K in the lungs of mice [34] . Our results were in concordance to these findings and implied the involvement of p-Akt pathway in the regulation of PDCD4 in ovarian cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Tumour Suppressive Function and Modulation of Programmed Cell Death 4 (PDCD4) in Ovarian Cancer

Wei

Liu

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

BackgroundProgrammed cell death 4 (PDCD4), originally identified as the neoplastic transformation inhibitor, was attenuated in various cancer types. Our previous study demonstrated a continuous down-regulation of PDCD4 expression in the sequence of normal-borderline-malignant ovarian tissue samples and a significant correlation of PDCD4 expression with disease-free survival. The objective of the current study was to further investigate the function and modulation of PDCD4 in ovarian cancer cells.Principal FindingsWe demonstrated that ectopic PDCD4 expression significantly inhibited cell proliferation by inducing cell cycle arrest at G1 stage and up-regulation of cell cycle inhibitors of p27 and p21. Cell migration and invasion were also inhibited by PDCD4. PDCD4 over-expressing cells exhibited elevated phosphatase and tensin homolog (PTEN) and inhibited protein kinase B (p-Akt). In addition, the expression of PDCD4 was up-regulated and it was exported to the cytoplasm upon serum withdrawal treatment, but it was rapidly depleted via proteasomal degradation upon serum re-administration. Treatment of a phosphoinositide 3-kinase (PI3K) inhibitor prevented the degradation of PDCD4, indicating the involvement of PI3K-Akt pathway in the modulation of PDCD4.ConclusionPDCD4 may play a critical function in arresting cell cycle progression at key checkpoint, thus inhibiting cell proliferation, as well as suppressing tumour metastasis. The PI3K-Akt pathway was implied to be involved in the regulation of PDCD4 degradation in ovarian cancer cells. In response to the stress condition, endogenous PDCD4 was able to shuttle between cell compartments to perform its diverted functions.

show abstract

Section: Discussionmentioning

confidence: 99%

Tumour Suppressive Function and Modulation of Programmed Cell Death 4 (PDCD4) in Ovarian Cancer

Wei

Liu

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Knockdown of CASC9 could downregulate PDCD4, while overexpression of CASC9 increased PDCD4 levels. PDCD4 is reported to be involved in apoptosis, proliferation and cell cycle [ 26 – 28 ]. Our previous work has also revealed that suppression of PDCD4 promotes G1/S transition of ESCC cells [ 24 ], which is consistent with present results in CASC9 knockdown cells.…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of lncRNA CASC9 promotes esophageal squamous cell carcinoma growth by negatively regulating PDCD4 expression through EZH2

et al. 2017

View full text Add to dashboard Cite

BackgroundAbnormal expression of numerous long non-coding RNAs (lncRNAs) has been reported in esophageal squamous cell carcinoma (ESCC) recently, but the great majority of their roles and mechanisms remain largely unclear. We aim to identify the critical ESCC-associated lncRNAs and elucidate the functions and mechanisms in detail.MethodsMicroarrays were used to analyze the differentially expressed lncRNAs in ESCC tissues. qRT-PCR was used to verify the result of microarrays. The effects of the most up-regulated lncRNA, cancer susceptibility candidate 9(CASC9), on cell growth, proliferation and cell cycle were investigated by in vivo and in vitro assays. Microarrays and recovery tests were used to discover the regulatory targets of CASC9. RNA FISH and subcellular fractionation assays were used to detect the subcellular location of CASC9. Finally, the mechanism of CASC9 regulating PDCD4 was explored by RIP, RNA-protein pull down and ChIP assays.ResultsESCC tissue microarrays showed that CASC9 was the most up-regulated lncRNA. qRT-PCR analysis indicated that CASC9 expression was positively associated with tumor size and TNM stage, and predicted poor overall survival of ESCC patients. Knockdown of CASC9 inhibited ESCC cell growth in vitro and tumorigenesis in nude mice. Furthermore interfering CASC9 decreased cell proliferation and blocked cell cycle G1/S transition. CASC9-associated microarrays indicated that PDCD4 might be the target of CASC9. Consistent with this, PDCD4 expression was negatively associated with CASC9 expression in ESCC tissues and predicted good prognosis. Manipulating CASC9 expression in ESCC cells altered both PDCD4 mRNA and protein levels and cell cycle arrest caused by CASC9 knockdown could be rescued by suppressing PDCD4 expression. CASC9 located both in the nucleus and cytoplasm. Mechanistically, enhancer of zeste homolog2 (EZH2) could bind to both CASC9 and PDCD4 promoter region. Interfering CASC9 reduced the enrichment of EZH2 and H3K27me3 in the PDCD4 promoter region.ConclusionsOur study firstly demonstrates that lncRNA CASC9 functions as an oncogene by negatively regulating PDCD4 expression through recruiting EZH2 and subsequently altering H3K27me3 level. Our study implicates lncRNA CASC9 as a valuable biomarker for ESCC diagnosis and prognosis.Electronic supplementary materialThe online version of this article (10.1186/s12943-017-0715-7) contains supplementary material, which is available to authorized users.

show abstract

“…The study conducted by Wu et al (31) demonstrated the negative correlation between CASC9 and programmed cell death protein 4 (PDCD4) in ESCC. PDCD4 is a tumor suppressor gene that participates in the regulation of apoptosis, proliferation and the cell cycle (32)(33)(34). Wu et al (31) further proposed that CASC9 may downregulate PDCD4 expression by recruiting histone-lysine N-methyltransferase EZH2 to augment the proliferative ability of ESCC.…”

Section: Discussionmentioning

confidence: 99%

The expression, significance and function of cancer susceptibility candidate�9 in lung squamous cell carcinoma: A bioinformatics and in�vitro investigation

Guo

Zeng

et al. 2019

Int J Oncol

View full text Add to dashboard Cite

The cancer susceptibility candidate 9 (CASC9) gene has been reported to exert an oncogenic effect in several types of cancer. However, its role in lung squamous cell carcinoma (LUSC) is unknown. Therefore, the present study examined the expression of CASC9 in LUSC and non-cancer tissues by reverse transcription-quantitative polymerase chain reaction assays and by data mining of high-throughput public databases, including The Cancer Genome Atlas, the Gene Expression Omnibus, ArrayExpress and the Cancer Cell Line Encyclopedia. In vitro experiments were conducted to investigate the effects of CASC9 on the viability and the proliferation of LUSC cells. Furthermore, consulting the alteration status of CASC9 in LUSC from cBioPortal, functional enrichment analysis of co-expressed genes, prediction of potential transcription factors, and inspection of adjacent protein-coding genes were conducted to explore the potential molecular mechanism of CASC9 in LUSC. The results revealed that CASC9 was overexpressed in LUSC tissue, and significantly associated with the malignant progression of LUSC. In vitro experiments demonstrated that CASC9 knockdown by RNA interference attenuated the viability and proliferation of LUSC cells. Multiple copies of CASC9 gene were detected in 4 of 179 available sequenced LUSC cases. A functional enrichment analysis of 200 co-expressed genes indicated that these genes were significantly associated with terms, including 'cell-cell junction organization', 'desmosome organization', 'epidermis development', 'Hippo signaling pathway', 'pathogenic Escherichia coli infection' and 'PID HIF1 TF pathway'. Three genes, Fos-related antigen 2 (FOSL2), SWI/SNF complex subunit SMARCC2, and transcription factor COE1 (EBF1), were predicted by lncRNAMap to be associated with CASC9. Among these, the expression of FOSL2 and EBF1 was positively and negatively correlated with the expression of CASC9, respectively. Two adjacent protein-coding genes, cysteine-rich secretory protein LCCL domain-containing 1 and hepatocyte nuclear factor 4-γ, were also positively correlated with CASC9 expression. In conclusion, the present data suggest that CASC9 serves as an oncogene in LUSC and may be a promising target for alternative therapeutic options for patients with this condition.

show abstract

Decreased Level of PDCD4 (Programmed Cell Death 4) Protein Activated Cell Proliferation in the Lung of A/J Mouse

Cited by 10 publications

References 28 publications

Tumour Suppressive Function and Modulation of Programmed Cell Death 4 (PDCD4) in Ovarian Cancer

Tumour Suppressive Function and Modulation of Programmed Cell Death 4 (PDCD4) in Ovarian Cancer

Up-regulation of lncRNA CASC9 promotes esophageal squamous cell carcinoma growth by negatively regulating PDCD4 expression through EZH2

The expression, significance and function of cancer susceptibility candidate�9 in lung squamous cell carcinoma: A bioinformatics and in�vitro investigation

Contact Info

Product

Resources

About