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- Publisher Website: 10.1186/1476-4598-12-119
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Article: MiR-23a-mediated inhibition of topoisomerase 1 expression potentiates cell response to etoposide in human hepatocellular carcinoma
Title | MiR-23a-mediated inhibition of topoisomerase 1 expression potentiates cell response to etoposide in human hepatocellular carcinoma |
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Authors | |
Keywords | DNA damage Etoposide Hepatocellular carcinoma miR-23a Topoisomerase 1 |
Issue Date | 2013 |
Publisher | BioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com |
Citation | Molecular Cancer, 2013, v. 12 n. 1, p. 119 How to Cite? |
Abstract | Background: microRNAs have been shown to regulate the chemosensitivity of cancer cells. The aim of this study is to investigate the role and mechanism of mir-23a in enhancing the anti-tumor effect of topoisomerase 2A (TOP2A) poison etoposide in human hepatocellular carcinoma (HCC). Methods: The anti-tumor effect of chemotherapeutic agents in HCC cells were examined in vitro and in vivo xenograft model. Expression of mRNA and miRNAs were determined by quantitative real-time PCR. Protein expression was analyzed by immunoblotting. Results: Overexpression of mir-23a could significantly potentiate the in vitro and in vivo anti-tumor effect of etoposide; however, ectopic expression of miR-23a fails to sensitize HCC cells to 5-fluorouracil treatment, indicating the miR-23a-induced cancer cell hypersensitivity in chemotherapy is TOP2A-specific though miR-23a overexpression could not directly up-regulate TOP2A expression. Topoisomerase 1(TOP1) is down-regulated in miR-23a-overexpressed HCC cells. MiR-23a could directly bind to 3′untranslated region of TOP1 mRNA, and suppress the corresponding protein expression and inhibition of miR-23a further arguments the expression of TOP1. MiR-23a was up-regulated during DNA damage in cancer cells in line with the p53 expression. Up-regulation of p53 induces mir-23a expression, while suppression of p53 inhibits miR-23a in HCC cells. Conclusion: Our study sheds light on the role of miR-23a as a potential target in regulating chemosensitivity of HCC cells. © 2013 Wang et al.; licensee BioMed Central Ltd. |
Persistent Identifier | http://hdl.handle.net/10722/195910 |
ISSN | 2023 Impact Factor: 27.7 2023 SCImago Journal Rankings: 8.222 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Wang, N | en_US |
dc.contributor.author | Zhu, M | en_US |
dc.contributor.author | Tsao, GSW | en_US |
dc.contributor.author | Man, K | en_US |
dc.contributor.author | Zhang, Z | en_US |
dc.contributor.author | Feng, Y | en_US |
dc.date.accessioned | 2014-03-21T02:18:27Z | - |
dc.date.available | 2014-03-21T02:18:27Z | - |
dc.date.issued | 2013 | en_US |
dc.identifier.citation | Molecular Cancer, 2013, v. 12 n. 1, p. 119 | en_US |
dc.identifier.issn | 1476-4598 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/195910 | - |
dc.description.abstract | Background: microRNAs have been shown to regulate the chemosensitivity of cancer cells. The aim of this study is to investigate the role and mechanism of mir-23a in enhancing the anti-tumor effect of topoisomerase 2A (TOP2A) poison etoposide in human hepatocellular carcinoma (HCC). Methods: The anti-tumor effect of chemotherapeutic agents in HCC cells were examined in vitro and in vivo xenograft model. Expression of mRNA and miRNAs were determined by quantitative real-time PCR. Protein expression was analyzed by immunoblotting. Results: Overexpression of mir-23a could significantly potentiate the in vitro and in vivo anti-tumor effect of etoposide; however, ectopic expression of miR-23a fails to sensitize HCC cells to 5-fluorouracil treatment, indicating the miR-23a-induced cancer cell hypersensitivity in chemotherapy is TOP2A-specific though miR-23a overexpression could not directly up-regulate TOP2A expression. Topoisomerase 1(TOP1) is down-regulated in miR-23a-overexpressed HCC cells. MiR-23a could directly bind to 3′untranslated region of TOP1 mRNA, and suppress the corresponding protein expression and inhibition of miR-23a further arguments the expression of TOP1. MiR-23a was up-regulated during DNA damage in cancer cells in line with the p53 expression. Up-regulation of p53 induces mir-23a expression, while suppression of p53 inhibits miR-23a in HCC cells. Conclusion: Our study sheds light on the role of miR-23a as a potential target in regulating chemosensitivity of HCC cells. © 2013 Wang et al.; licensee BioMed Central Ltd. | - |
dc.language | eng | en_US |
dc.publisher | BioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com | en_US |
dc.relation.ispartof | Molecular Cancer | en_US |
dc.rights | Molecular Cancer. Copyright © BioMed Central Ltd. | en_US |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | DNA damage | - |
dc.subject | Etoposide | - |
dc.subject | Hepatocellular carcinoma | - |
dc.subject | miR-23a | - |
dc.subject | Topoisomerase 1 | - |
dc.title | MiR-23a-mediated inhibition of topoisomerase 1 expression potentiates cell response to etoposide in human hepatocellular carcinoma | en_US |
dc.type | Article | en_US |
dc.identifier.email | Wang, N: ckwang@hku.hk | en_US |
dc.identifier.email | Zhu, M: mfzhu@hku.hk | en_US |
dc.identifier.email | Tsao, GSW: gswtsao@hku.hk | en_US |
dc.identifier.email | Man, K: kwanman@hku.hk | en_US |
dc.identifier.email | Zhang, Z: zhangzj@hkucc.hku.hk | en_US |
dc.identifier.email | Feng, Y: yfeng@hku.hk | en_US |
dc.identifier.authority | Tsao, GSW=rp00399 | en_US |
dc.identifier.authority | Man, K=rp00417 | en_US |
dc.identifier.authority | Zhang, Z=rp01297 | en_US |
dc.identifier.authority | Feng, Y=rp00466 | en_US |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1186/1476-4598-12-119 | en_US |
dc.identifier.pmid | 24103454 | - |
dc.identifier.pmcid | PMC3856574 | - |
dc.identifier.scopus | eid_2-s2.0-84885000772 | - |
dc.identifier.hkuros | 228307 | en_US |
dc.identifier.hkuros | 226724 | - |
dc.identifier.volume | 12 | en_US |
dc.identifier.issue | 1 | en_US |
dc.identifier.spage | 119 | en_US |
dc.identifier.epage | 119 | en_US |
dc.identifier.isi | WOS:000326288400002 | - |
dc.publisher.place | United Kingdom | en_US |
dc.identifier.issnl | 1476-4598 | - |