Profiling MicroRNA Expression in Hepatocellular Carcinoma Reveals MicroRNA-224 Up-regulation and Apoptosis Inhibitor-5 as a MicroRNA-224-specific Target
Like other cancers, aberrant gene regulation features significantly in hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) were recently found to regulate gene expression at the post-transcriptional/translational levels. The expression profiles of 157 miRNAs were examined in 19 HCC patients, and 19 u...
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| Veröffentlicht in: | The Journal of biological chemistry 2008-05, Vol.283 (19), p.13205-13215 |
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| container_title | The Journal of biological chemistry |
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| creator | Wang, Yu Lee, Alvin T.C. Ma, Joel Z.I. Wang, Jingbo Ren, Jianwei Yang, Yuchen Tantoso, Erwin Li, Kuo-Bin Ooi, London L. P. J Tan, Patrick Lee, Caroline G.L. |
| description | Like other cancers, aberrant gene regulation features significantly in hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) were recently found to regulate gene expression at the post-transcriptional/translational levels. The expression profiles of 157 miRNAs were examined in 19 HCC patients, and 19 up-regulated and 3 down-regulated miRNAs were found to be associated with HCC. Putative gene targets of these 22 miRNAs were predicted in silico and were significantly enriched in 34 biological pathways, most of which are frequently dysregulated during carcinogenesis. Further characterization of microRNA-224 (miR-224), the most significantly up-regulated miRNA in HCC patients, revealed that miR-224 increases apoptotic cell death as well as proliferation and targets apoptosis inhibitor-5 (API-5) to inhibit API-5 transcript expression. Significantly, miR-224 expression was found to be inversely correlated with API-5 expression in HCC patients (p < 0.05). Hence, our findings define a true in vivo target of miR-224 and reaffirm the important role of miRNAs in the dysregulation of cellular processes that may ultimately lead to tumorigenesis. |
| doi_str_mv | 10.1074/jbc.M707629200 |
| format | Article |
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P. J ; Tan, Patrick ; Lee, Caroline G.L.</creator><creatorcontrib>Wang, Yu ; Lee, Alvin T.C. ; Ma, Joel Z.I. ; Wang, Jingbo ; Ren, Jianwei ; Yang, Yuchen ; Tantoso, Erwin ; Li, Kuo-Bin ; Ooi, London L. P. J ; Tan, Patrick ; Lee, Caroline G.L.</creatorcontrib><description>Like other cancers, aberrant gene regulation features significantly in hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) were recently found to regulate gene expression at the post-transcriptional/translational levels. The expression profiles of 157 miRNAs were examined in 19 HCC patients, and 19 up-regulated and 3 down-regulated miRNAs were found to be associated with HCC. Putative gene targets of these 22 miRNAs were predicted in silico and were significantly enriched in 34 biological pathways, most of which are frequently dysregulated during carcinogenesis. Further characterization of microRNA-224 (miR-224), the most significantly up-regulated miRNA in HCC patients, revealed that miR-224 increases apoptotic cell death as well as proliferation and targets apoptosis inhibitor-5 (API-5) to inhibit API-5 transcript expression. Significantly, miR-224 expression was found to be inversely correlated with API-5 expression in HCC patients (p < 0.05). Hence, our findings define a true in vivo target of miR-224 and reaffirm the important role of miRNAs in the dysregulation of cellular processes that may ultimately lead to tumorigenesis.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M707629200</identifier><identifier>PMID: 18319255</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Apoptosis ; Apoptosis Regulatory Proteins - genetics ; Base Sequence ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - pathology ; Cell Transformation, Neoplastic - genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic - genetics ; Humans ; MicroRNAs - genetics ; Molecular Sequence Data ; Nuclear Proteins - genetics ; Substrate Specificity ; Transcription, Genetic - genetics ; Tumor Cells, Cultured ; Up-Regulation - genetics</subject><ispartof>The Journal of biological chemistry, 2008-05, Vol.283 (19), p.13205-13215</ispartof><rights>2008 © 2008 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-e0943fb5b6ab296dc75ebcc2fc192632d93af1ab8b9464b04e138e9fade2c43f3</citedby><cites>FETCH-LOGICAL-c532t-e0943fb5b6ab296dc75ebcc2fc192632d93af1ab8b9464b04e138e9fade2c43f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18319255$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yu</creatorcontrib><creatorcontrib>Lee, Alvin T.C.</creatorcontrib><creatorcontrib>Ma, Joel Z.I.</creatorcontrib><creatorcontrib>Wang, Jingbo</creatorcontrib><creatorcontrib>Ren, Jianwei</creatorcontrib><creatorcontrib>Yang, Yuchen</creatorcontrib><creatorcontrib>Tantoso, Erwin</creatorcontrib><creatorcontrib>Li, Kuo-Bin</creatorcontrib><creatorcontrib>Ooi, London L. P. J</creatorcontrib><creatorcontrib>Tan, Patrick</creatorcontrib><creatorcontrib>Lee, Caroline G.L.</creatorcontrib><title>Profiling MicroRNA Expression in Hepatocellular Carcinoma Reveals MicroRNA-224 Up-regulation and Apoptosis Inhibitor-5 as a MicroRNA-224-specific Target</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Like other cancers, aberrant gene regulation features significantly in hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) were recently found to regulate gene expression at the post-transcriptional/translational levels. The expression profiles of 157 miRNAs were examined in 19 HCC patients, and 19 up-regulated and 3 down-regulated miRNAs were found to be associated with HCC. Putative gene targets of these 22 miRNAs were predicted in silico and were significantly enriched in 34 biological pathways, most of which are frequently dysregulated during carcinogenesis. Further characterization of microRNA-224 (miR-224), the most significantly up-regulated miRNA in HCC patients, revealed that miR-224 increases apoptotic cell death as well as proliferation and targets apoptosis inhibitor-5 (API-5) to inhibit API-5 transcript expression. Significantly, miR-224 expression was found to be inversely correlated with API-5 expression in HCC patients (p < 0.05). Hence, our findings define a true in vivo target of miR-224 and reaffirm the important role of miRNAs in the dysregulation of cellular processes that may ultimately lead to tumorigenesis.</description><subject>Apoptosis</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Base Sequence</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Humans</subject><subject>MicroRNAs - genetics</subject><subject>Molecular Sequence Data</subject><subject>Nuclear Proteins - genetics</subject><subject>Substrate Specificity</subject><subject>Transcription, Genetic - genetics</subject><subject>Tumor Cells, Cultured</subject><subject>Up-Regulation - genetics</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1u1DAUhS0EokNhyxK8QN1l8E-ScZajUWkrtYBKR2Jn2c5N5laZOLUzBd6Ex8VRRlQs8MKWrO8cnXsPIW85W3K2yj_eW7e8WbFVKSrB2DOy4EzJTBb8-3OyYEzwrBKFOiGvYrxn6eQVf0lOuJI8_RcL8vtr8A122Lf0Bl3wt5_X9PznECBG9D3Fnl7CYEbvoOsOnQl0Y4LD3u8NvYVHMF38q8uEyOl2yAK0iRwnuelruh78MPqIkV71O7Q4-pAV1ERq_lFmcQCHDTp6Z0IL42vyoknu8Ob4npLtp_O7zWV2_eXiarO-zlwhxZgBq3LZ2MKWxoqqrN2qAOucaFwasJSirqRpuLHKVnmZW5YDlwqqxtQgXFLKU3I2-w7BPxwgjnqPcZrW9OAPUQtWlqVQKoHLGUyZYwzQ6CHg3oRfmjM9daFTF_qpiyR4d3Q-2D3UT_hx-Qn4MAM7bHc_MIC26N0O9looqXmluRRswt7PWGO8Nm3AqLffBOOSMVWle4qmZgLSoh4Rgo4OoXdQJ1M36trj_0L-AWuZrdo</recordid><startdate>20080509</startdate><enddate>20080509</enddate><creator>Wang, Yu</creator><creator>Lee, Alvin T.C.</creator><creator>Ma, Joel Z.I.</creator><creator>Wang, Jingbo</creator><creator>Ren, Jianwei</creator><creator>Yang, Yuchen</creator><creator>Tantoso, Erwin</creator><creator>Li, Kuo-Bin</creator><creator>Ooi, London L. P. J</creator><creator>Tan, Patrick</creator><creator>Lee, Caroline G.L.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope></search><sort><creationdate>20080509</creationdate><title>Profiling MicroRNA Expression in Hepatocellular Carcinoma Reveals MicroRNA-224 Up-regulation and Apoptosis Inhibitor-5 as a MicroRNA-224-specific Target</title><author>Wang, Yu ; Lee, Alvin T.C. ; Ma, Joel Z.I. ; Wang, Jingbo ; Ren, Jianwei ; Yang, Yuchen ; Tantoso, Erwin ; Li, Kuo-Bin ; Ooi, London L. P. 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P. J</creatorcontrib><creatorcontrib>Tan, Patrick</creatorcontrib><creatorcontrib>Lee, Caroline G.L.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yu</au><au>Lee, Alvin T.C.</au><au>Ma, Joel Z.I.</au><au>Wang, Jingbo</au><au>Ren, Jianwei</au><au>Yang, Yuchen</au><au>Tantoso, Erwin</au><au>Li, Kuo-Bin</au><au>Ooi, London L. P. 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Putative gene targets of these 22 miRNAs were predicted in silico and were significantly enriched in 34 biological pathways, most of which are frequently dysregulated during carcinogenesis. Further characterization of microRNA-224 (miR-224), the most significantly up-regulated miRNA in HCC patients, revealed that miR-224 increases apoptotic cell death as well as proliferation and targets apoptosis inhibitor-5 (API-5) to inhibit API-5 transcript expression. Significantly, miR-224 expression was found to be inversely correlated with API-5 expression in HCC patients (p < 0.05). Hence, our findings define a true in vivo target of miR-224 and reaffirm the important role of miRNAs in the dysregulation of cellular processes that may ultimately lead to tumorigenesis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>18319255</pmid><doi>10.1074/jbc.M707629200</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis Apoptosis Regulatory Proteins - genetics Base Sequence Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - pathology Cell Transformation, Neoplastic - genetics Gene Expression Profiling Gene Expression Regulation, Neoplastic - genetics Humans MicroRNAs - genetics Molecular Sequence Data Nuclear Proteins - genetics Substrate Specificity Transcription, Genetic - genetics Tumor Cells, Cultured Up-Regulation - genetics |
| title | Profiling MicroRNA Expression in Hepatocellular Carcinoma Reveals MicroRNA-224 Up-regulation and Apoptosis Inhibitor-5 as a MicroRNA-224-specific Target |
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