Knockdown of S100P by lentiviral-mediated RNAi promotes apoptosis and suppresses the colony-formation ability of gastric cancer cells

Zhang, Qi; Hu, Hongzhi; Shi, Xin; Tang, Wen-hao

doi:10.3892/or.2014.3104

Cited by 14 publications

(14 citation statements)

References 22 publications

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“…Over‐expression of S100P in prostate cancer cells could protect against camptothecin‐induced apoptosis . The RNA interference‐mediated down‐regulation of S100P expression markedly promoted cell apoptosis and inhibited cell colony‐formation ability of the gastric cancer cells . In the present study, the shRNA‐medicated S100P promoted the apoptosis of CCA cells and induced the changed expression of the apoptosis related factors, including the up‐regulated expression of death receptor DR5 and its downstream factor TRADD and caspase 3, which initials Trail‐induced apoptosis .…”

Section: Discussionsupporting

confidence: 52%

“…14 The RNA interference-mediated down-regulation of S100P expression markedly promoted cell apoptosis and inhibited cell colony-formation ability of the gastric cancer cells. 43 In the present study, the shRNA-medicated S100P promoted the apoptosis of CCA cells and induced the changed expression of the apoptosis related factors, including the up-regulated expression of death receptor DR5 and its downstream factor TRADD and caspase 3, which initials Trail-induced apoptosis. 44 The results suggest that knockdown of S100P may promote apoptosis via TRAIL signal pathway, which may be a potential anticancer agent of CCA as reported.…”

Section: Discussionmentioning

confidence: 48%

See 1 more Smart Citation

Significance of S100P as a biomarker in diagnosis, prognosis and therapy of opisthorchiasis‐associated cholangiocarcinoma

Boonmars

Nagano

et al. 2015

Intl Journal of Cancer

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Cholangiocarcinoma (CCA) is a malignancy of bile duct with the difficulty in early diagnosis, poor prognosis and less alternation in therapy. S100P is a member of S100 family proteins and plays important roles in cancers. We investigated the S100P expression and its correlation with clinicopathology in 78 cases of opisthorchiasis-associated CCA, and the effects of S100P knockdown with shRNA interference on the proliferation, cell cycle, migration, apoptosis and sensitivity to anti-cancer drug. Extremely high expression of S100P mRNA was detected in the CCA tumor tissues. The increased S100P protein expression was immunohistochemically confirmed and localized in the CCA cytoplasm and/or nuclei as well as in the hyperneoplasia and dysplasia bile ducts, but not in normal bile ducts. The intensity of immunostaining was correlated with survival, tumor stage and metastasis, and the high expression could be an independent prognostic factor. High levels of S100P were detected in the serum and bile fluid of CCA patients. The shRNA-mediated knockdown of S100P expression inhibited the proliferation in vitro and in vivo, and migration of CCA cells, arrested cell cycle with the up-regulated expression of cell cycle arrest related factors, p21, p27, GADD45A, and 14-3-3 zeta. S100P knockdown also promoted CCA cell apoptosis by up-regulating expression of apoptosis related factors, DR5, TRADD, caspase 3 and BAX, and increased the sensitivity of CCA cells to the chemotherapeutic agents sunitinib and apigenin. Taken together, this study indicates that S100P might be a promising biomarker for the diagnosis, prognosis and therapy of CCA.Cholangiocarcinoma (CCA) is a malignancy arising from bile ducts. Although it is rare, the incidence and mortality of the cancer have been increasing worldwide over the past decades, while the prognosis is remained dismal and substantially unchanged.1 Because of the lack of the method of early diagnosis, most of patients, when diagnosed, are incurable advanced and metastatic; their 5-year survival rate is extremely low. Chronic inflammation is one of important risks of CCA tumorigenesis, including Opisthorchis viverrini infection. Clear relationship between O. viverrini infection and CCA incidence has been demonstrated.2,3 The epidemiological investigations have indicated the astonished high incidence of CCA in opisthorchiasis endemic areas, especially in northeast of Thailand where both opisthorchiasis prevalence and CCA incidence are the highest in the world. 4,5 Serious O. viverrini infection, the lack of early diagnostic methods and poor prognosis of CCA put the millions of people at the risk of CCA in endemic areas. Although many efforts have been made, the biomarkers for diagnosis, prognosis and therapy of CCA are still quite limited. Therefore, it is urgent to delve into the tumorigenesis mechanism and develop novel biomarkers for the early diagnosis, prognosis, and therapy of the opisthorchiasis-associated CCA.Our previous cDNA microarray analysis showed that some of S100 proteins were up-re...

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 48%

Significance of S100P as a biomarker in diagnosis, prognosis and therapy of opisthorchiasis‐associated cholangiocarcinoma

Boonmars

Nagano

et al. 2015

Intl Journal of Cancer

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“…CST1 and S100P were selected for further validation based on previous studies revealing the role of those two genes in gastric carcinogenesis. For example, CST1 was revealed to increase cell proliferation (25) and S100P to regulate cell proliferation (26) and colony formation (27) in gastric cancer; these two genes exhibited oncogenic roles in other cancers as well (28–33). Altogether, CST1 regulated by HOXC10 contributes to gastric cancer development, and these two genes could be potential prognostic markers for gastric cancer.…”

Section: Resultsmentioning

confidence: 99%

HOXC10 overexpression promotes cell proliferation and migration in gastric cancer

et al. 2019

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Homeodomain-containing gene 10 ( HOXC10 ) is a member of the homeobox transcription factors that plays an important role in the development of multicellular organisms. HOXC10 is overexpressed in a variety of human cancers, and recent studies have revealed that HOXC10 is upregulated in gastric cancer as well. However, its mechanism of action is not fully understood, thus, the role of HOXC10 was investigated in the present study in human gastric cancer. First, HOXC10 expression was revealed to be significantly increased in gastric cancer tissues compared to normal tissues (TCGA dataset), and HOXC10 upregulation was associated with decreased recurrence-free survival in gastric cancer patients in a public gene expression dataset. HOXC10 promoted cell proliferation and metastasis in two gastric cancer cell lines (AGS and MKN74). Analyzing TCGA 450K DNA methylation dataset, it was revealed that HOXC10 CpG sites were hypomethylated in gastric cancer tissues. Bisulfite sequencing revealed that CpG sites in the HOXC10 first intronic region were hypomethylated in three gastric cancer tissues, and HOXC10 expression was increased in gastric cancer cell lines (AGS and SNU620) in response to 5-azacytidine treatment. By RNA-sequencing of AGS cells with ectopic HOXC10 expression, it was revealed that many genes were upregulated by HOXC10 overexpression. Among them, CST1 was predicted to be a HOXC10 direct target gene via prediction of HOXC10 binding sites from the JASPAR database. A chromatin immunoprecipitation assay revealed that HOXC10 directly bound to CST1 promoter regions. The present study proposes HOXC10 is a potential prognostic marker or therapeutic target in human gastric cancer.

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“…The Wnt/b-catenin pathway, when activated, is sufficient to cause hepatocellular carcinoma and hepatoblastoma, suggesting that this pathway plays an important role in liver carcinogenesis (Mokkapati et al, 2014). In gastric cancer cells, both b-catenin and DAPK1 expression was regulated by S100P, which is an oncogenic factor in gastric cancer (Zhang et al, 2014). The mechanistic insights for how DAPK1 is regulated by b-catenin in liver cancer may result in novel therapeutic approach in treatment of liver cancer.…”

Section: Discussionmentioning

confidence: 99%

DAPK1 as an independent prognostic marker in liver cancer

Guo

Wang

et al. 2017

PeerJ

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The death-associated protein kinase 1 (DAPK1) can act as an oncogene or a tumor suppressor gene depending on the cellular context as well as external stimuli. Our study aims to investigate the prognostic significance of DAPK1 in liver cancer in both mRNA and protein levels. The mRNA expression of DAPK1 was extracted from the Gene Expression Omnibus database in three independent liver cancer datasets while protein expression of DAPK1 was detected by immunohistochemistry in our Chinese liver cancer patient cohort. The associations between DAPK1 expression and clinical characteristics were tested. DAPK1 mRNA expression was down-regulated in liver cancer. Low levels of DAPK1 mRNA were associated with shorter survival in a liver cancer patient cohort (n = 115; p = 0.041), while negative staining of DAPK1 protein was significantly correlated with shorter time to progression (p = 0.002) and overall survival (p = 0.02). DAPK1 was an independent prognostic marker for both time to progression and overall survival by multivariate analysis. Liver cancer with the b-catenin mutation has a lower DAPK1 expression, suggesting that DAPK1 may be regulated under the b-catenin pathway. In addition, we also identified genes that are co-regulated with DAPK1. DAPK1 expression was positively correlated with IRF2, IL7R, PCOLCE and ZBTB16, and negatively correlated with SLC16A3 in both liver cancer datasets. Among these genes, PCOLCE and ZBTB16 were significantly down-regulated, while SLC16A3 was significantly upregulated in liver cancer. By using connectivity mapping of these co-regulated genes, we have identified amcinonide and sulpiride as potential small molecules that could potentially reverse DAPK1/PCOLCE/ZBTB16/SLC16A3 expression. Our study demonstrated for the first time that both DAPK1 mRNA and protein expression levels are important prognostic markers in liver cancer, and have identified genes that may contribute to DAPK1-mediated liver carcinogenesis.

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Knockdown of S100P by lentiviral-mediated RNAi promotes apoptosis and suppresses the colony-formation ability of gastric cancer cells

Cited by 14 publications

References 22 publications

Significance of S100P as a biomarker in diagnosis, prognosis and therapy of opisthorchiasis‐associated cholangiocarcinoma

Significance of S100P as a biomarker in diagnosis, prognosis and therapy of opisthorchiasis‐associated cholangiocarcinoma

HOXC10 overexpression promotes cell proliferation and migration in gastric cancer

DAPK1 as an independent prognostic marker in liver cancer

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