Overexpression of tumor suppressor TSLC1 by a survivin-regulated oncolytic adenovirus significantly inhibits hepatocellular carcinoma growth

He, Gang; Lei, Wen; Wang, Shibin; Xiao, Ruijuan; Guo, Keni; Xia, Yu-long; Zhou, Xiumei; Zhang, Kangjian; Liu, Xinyuan; Wang, Yigang

doi:10.1007/s00432-011-1138-2

Cited by 35 publications

(23 citation statements)

References 36 publications

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“…Our study is the first to report miR-1246 could regulate invasion and migration of HCC cell via targeting CADM1. There is no doubt that CADM1 functions as a tumor suppressor gene in HCC [23, 28]. In this study, we also demonstrated that CADM1 RNA interference results in up-regulation of invasion and migration in HCC cell lines.…”

Section: Discussionsupporting

confidence: 70%

MicroRNA-1246 enhances migration and invasion through CADM1 in hepatocellular carcinoma

et al. 2014

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BackgroundThe aberrant expression of microRNAs has been demonstrated to play a crucial role in the initiation and progression of hepatocarcinoma. miR-1246 expression in High invasive ability cell line than significantly higher than that in low invasive ability cell line.MethodsTranswell chambers (8-uM pore size; Costar) were used in the in vitro migration and invison anssay. Dual luciferase reporter gene construct and Dual luciferase reporter assay to identify the target of miR-1246. CADM1 expression was evaluated by immunohistochemistric staining. The clinical manifestations, treatments and survival were collected for statistical analysis.ResultsInhibition of miR-1246 effectively reduced migration and invasion of hepatocellular carcinoma cell lines. Bioinformatics and luciferase reporter assay revealed that miR-1246 specifically targeted the 3′-UTR of Cell adhesion molecule 1 and regulated its expression. Down-regulation of CADM1 enhanced migration and invasion of HCC cell lines. Furthermore, in tumor tissues obtained from liver cancer patients, the expression of miR-1246 was negatively correlated with CADM1 and the high expression of miR-1246 combined with low expression of CADM1 might serve as a risk factor for stage1 liver cancer patients.ConclusionsOur study showed that miR-1246, by down-regulation CADM1, enhances migration and invasion in HCC cells.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-616) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 70%

MicroRNA-1246 enhances migration and invasion through CADM1 in hepatocellular carcinoma

et al. 2014

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“…Tsujiuchi et al reported that in HCC induced by N-nitrosodiethylamine, the 5’ upstream region of TSLC1 was methylated and its expression was reduced [18]. Additionally, some researchers reported that restoration of TSLC1 could effectively inhibit HCC growth [28]. In the present study, we were the first to identify TSLC1 as a direct target of miRNA-873 in HCC cells.…”

Section: Discussionmentioning

confidence: 70%

MicroRNA-873 Promotes Cell Proliferation, Migration, and Invasion by Directly Targeting TSLC1 in Hepatocellular Carcinoma

Han¹,

Zhang²,

Ni³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has the third highest mortality rate among all cancers. MicroRNAs are a class of endogenous, single-stranded short noncoding RNAs. The purpose of this study was to study the role of microRNA-873 in HCC. Methods: The expression of miRNA-873 and tumor suppressor in lung cancer 1 (TSLC1) in HCC tissues and cell lines was detected by real-time quantitative RT-PCR (RT-qPCR) or western blot. A CCK-8 assay was used to examine cell proliferation; flow cytometry was used to assess the cell cycle; the Transwell migration assay was used to test for metastasis. Luciferase assays were performed to assess whether TSLC1 was a novel target of miRNA-873. Results: We showed that miRNA-873 was upregulated in HCC tissues and cell lines compared with the normal control. Knockdown of miRNA-873 inhibited the growth and metastasis of HepG2 and accelerated G1 phase arrest, while overexpression of miRNA-873 had the opposite effect. The dual-luciferase reporter assays revealed that TSLC1 was a novel target of miRNA-873. Further study showed that TSLC1 was decreased in HCC tissues and cell lines. There was a negative correlation between the expression levels of TSLC1 and miRNA-873. The effect of miRNA-873 overexpression was neutralized by TSLC1. We also found that miRNA-873 activated the PI3K/AKT/mTOR signaling pathway and promoted HCC. Conclusions: Our data demonstrated that miRNA-873 promoted HCC progression by targeting TSLC1 and provided a new target for the therapy of HCC.

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“…Thus, TSLC1 mediates potential anti-cancer effects. Notably, our previous study reported that OA encoding TSLC1 exhibits significant antitumor effects on hepatocellular cancer cells [25] . The differences between these studies include the OA design and the cancer types investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Of significance, survivin has aberrantly high expression in cancer cells such as lung cancer but little expression in most normal tissues, making survivin an attractive anticancer target [22,23] . Recent studies have shown that a designed oncolytic adenovirus driven by the survivin promoter exhibited a tumor-selective antitumor effect in vitro and in vivo [3,24,25] , suggesting that the survivin promoter is a good candidate for cancer therapy. To improve the OA tumor-specificity, a 24 bp region within the E1A conserved region 2 (CR2), which is responsible for binding the retinoblastoma (Rb) protein, was deleted.…”

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confidence: 99%

Tumor suppressor in lung cancer-1 (TSLC1) mediated by dual-regulated oncolytic adenovirus exerts specific antitumor actions in a mouse model

et al. 2013

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Aim:The tumor suppressor in lung cancer-1 (TSLC1) is a candidate tumor suppressor of lung cancer, and frequently inactivated in primary non-small cell lung cancer (NSCLC). In this study, we investigated the effects of TSLC1 mediated by a dual-regulated oncolytic adenovirus on lung cancer, and the mechanisms underlying the antitumor actions. Methods: The recombinant virus Ad·sp-E1A (∆24) -TSLC1 was constructed by inserting the TSLC1 gene into the dual-regulated Ad·sp-E1A (∆24) vector, which contained the survivin promoter and a 24 bp deletion within E1A. The antitumor effects of Ad·sp-E1A (∆24) -TSLC1 were evaluated in NCI-H460, A549, and H1299 lung cancer cell lines and the normal fibroblast cell line MRC-5, as well as in A549 xenograft model in nude mice. Cell viability was assessed using MTT assay. The expression of TSLC1 and activation of the caspase signaling pathway were detected by Western blot analyses. The tumor tissues from the xenograft models were examined using H&E staining, IHC, TUNEL, and TEM analyses. Results: Infection of A549 lung cancer cells with Ad·sp-E1A (∆24) -TSLC1 induced high level expression of TSLC1. Furthermore, the Ad·sp-E1A (∆24) -TSLC1 virus dose-dependently suppressed the viability of NCI-H460, A549, and H1299 lung cancer cells, and did not affect MRC-5 normal fibroblast cells. Infection of NCI-H460, A549, and H1299 lung cancer cells with Ad·sp-E1A (∆24) -TSLC1 induced apoptosis, and increased activation of caspase-8, caspase-3 and PARP. In A549 xenograft model in nude mice, intratumoral injection of Ad·sp-E1A (∆24) -TSLC1 significantly suppressed the tumor volume, and increased the survival rate (from less than 15% to 87.5% at d 60). Histological studies showed that injection of Ad·sp-E1A (∆24) -TSLC1 caused tumor cell apoptosis and virus particle propagation in tumor tissues. Conclusion: The oncolytic adenovirus Ad·sp-E1A (∆24) -TSLC1 exhibits specific antitumor effects, and is a promising agent for the treatment of lung cancer.

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Overexpression of tumor suppressor TSLC1 by a survivin-regulated oncolytic adenovirus significantly inhibits hepatocellular carcinoma growth

Abstract: These data suggest that an oncolytic adenovirus expressing TSLC1 is effective and support that SD55-TSLC1 may be a potent antitumoral agent for future clinical trials of liver cancer.

Cited by 35 publications

References 36 publications

MicroRNA-1246 enhances migration and invasion through CADM1 in hepatocellular carcinoma

MicroRNA-1246 enhances migration and invasion through CADM1 in hepatocellular carcinoma

MicroRNA-873 Promotes Cell Proliferation, Migration, and Invasion by Directly Targeting TSLC1 in Hepatocellular Carcinoma

Tumor suppressor in lung cancer-1 (TSLC1) mediated by dual-regulated oncolytic adenovirus exerts specific antitumor actions in a mouse model

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