Please use this identifier to cite or link to this item:
https://doi.org/10.18632/oncotarget.3234
DC Field | Value | |
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dc.title | Decreased miR122 in hepatocellular carcinoma leads to chemoresistance with increased arginine | |
dc.contributor.author | Kishikawa, T | |
dc.contributor.author | Otsuka, M | |
dc.contributor.author | Tan, P.S | |
dc.contributor.author | Ohno, M | |
dc.contributor.author | Sun, X | |
dc.contributor.author | Yoshikawa, T | |
dc.contributor.author | Shibata, C | |
dc.contributor.author | Takata, A | |
dc.contributor.author | Kojima, K | |
dc.contributor.author | Takehana, K | |
dc.contributor.author | Ohishi, M | |
dc.contributor.author | Ota, S | |
dc.contributor.author | Noyama, T | |
dc.contributor.author | Kondo, Y | |
dc.contributor.author | Sato, M | |
dc.contributor.author | Soga, T | |
dc.contributor.author | Hoshida, Y | |
dc.contributor.author | Koike, K | |
dc.date.accessioned | 2020-10-27T05:51:13Z | |
dc.date.available | 2020-10-27T05:51:13Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Kishikawa, T, Otsuka, M, Tan, P.S, Ohno, M, Sun, X, Yoshikawa, T, Shibata, C, Takata, A, Kojima, K, Takehana, K, Ohishi, M, Ota, S, Noyama, T, Kondo, Y, Sato, M, Soga, T, Hoshida, Y, Koike, K (2015). Decreased miR122 in hepatocellular carcinoma leads to chemoresistance with increased arginine. Oncotarget 6 (10) : 8339-8352. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.3234 | |
dc.identifier.issn | 19492553 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/180954 | |
dc.description.abstract | Reduced expression of microRNA122 (miR122), a liver-specific microRNA, is frequent in hepatocellular carcinoma (HCC). However, its biological significances remain poorly understood. Because deregulated amino acid levels in cancers can affect their biological behavior, we determined the amino acid levels in miR122- silenced mouse liver tissues, in which intracellular arginine levels were significantly increased. The increased intracellular arginine levels were through upregulation of the solute carrier family 7 (SLC7A1), a transporter of arginine and a direct target of miR122. Arginine is the substrate for nitric oxide (NO) synthetase, and intracellular NO levels were increased in miR122-silenced HCC cells, with increased resistance to sorafenib, a multikinase inhibitor. Conversely, maintenance of the miR122-silenced HCC cells in arginine-depleted culture media, as well as overexpression of miR122 in miR122-low-expressing HCC cells, reversed these effects and rendered the cells more sensitive to sorafenib. Using a reporter knock-in construct, chemical compounds were screened, and Wee1 kinase inhibitor was identified as upregulators of miR122 transcription, which increased the sensitivity of the cells to sorafenib. These results provide an insight into sorafenib resistance in miR122-low HCC, and suggest that arginine depletion or a combination of sorafenib with the identified compound may provide promising approaches to managing this HCC subset. | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | amino acid transporter | |
dc.subject | arginine | |
dc.subject | carrier protein | |
dc.subject | ellipticine | |
dc.subject | microRNA 122 | |
dc.subject | nitric oxide | |
dc.subject | nitric oxide synthase | |
dc.subject | pd 407824 | |
dc.subject | protein kinase inhibitor | |
dc.subject | sorafenib | |
dc.subject | unclassified drug | |
dc.subject | arginine | |
dc.subject | carbanilamide derivative | |
dc.subject | microRNA | |
dc.subject | MIRN122 microRNA, human | |
dc.subject | nicotinamide | |
dc.subject | sorafenib | |
dc.subject | animal tissue | |
dc.subject | Article | |
dc.subject | cancer resistance | |
dc.subject | cell level | |
dc.subject | controlled study | |
dc.subject | drug screening | |
dc.subject | drug sensitivity | |
dc.subject | gene silencing | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | liver cancer cell line | |
dc.subject | liver cell carcinoma | |
dc.subject | mouse | |
dc.subject | nonhuman | |
dc.subject | upregulation | |
dc.subject | analogs and derivatives | |
dc.subject | animal | |
dc.subject | apoptosis | |
dc.subject | biosynthesis | |
dc.subject | C57BL mouse | |
dc.subject | Carcinoma, Hepatocellular | |
dc.subject | deficiency | |
dc.subject | drug resistance | |
dc.subject | genetics | |
dc.subject | Liver Neoplasms | |
dc.subject | metabolism | |
dc.subject | pathology | |
dc.subject | physiology | |
dc.subject | transgenic mouse | |
dc.subject | tumor cell line | |
dc.subject | Animals | |
dc.subject | Apoptosis | |
dc.subject | Arginine | |
dc.subject | Carcinoma, Hepatocellular | |
dc.subject | Cell Line, Tumor | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Humans | |
dc.subject | Liver Neoplasms | |
dc.subject | Mice | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Mice, Transgenic | |
dc.subject | MicroRNAs | |
dc.subject | Niacinamide | |
dc.subject | Phenylurea Compounds | |
dc.type | Article | |
dc.contributor.department | MEDICINE | |
dc.description.doi | 10.18632/oncotarget.3234 | |
dc.description.sourcetitle | Oncotarget | |
dc.description.volume | 6 | |
dc.description.issue | 10 | |
dc.description.page | 8339-8352 | |
Appears in Collections: | Staff Publications Elements |
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