Metabolomic analyses in microRNA-reduced HCC

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460979
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: KOndo Yuji 東京大学, 医学部附属病院, 助教 (00572231)
• Co-Investigator(Kenkyū-buntansha): 大塚 基之 東京大学, 医学部附属病院, 助教 (90518945)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 肝臓学 / microRNA

Outline of Final Research Achievements

Reduced expression of microRNA122 (miR122) is frequently observed in hepatocellular carcinoma (HCC) with aggressive phenotype. However, the molecular mechanisms underlying these observations are not well understood. Using comprehensive metabolomic analyses, we found that the intracellular levels of arginine were increased in miR122-silenced transgenic mouse liver tissues, through upregulation of cationic amino acid transporter member 1 (CAT1), a transporter of arginine. Arginine is the substrate for nitric oxide synthetase, and intracellular NO levels were indeed increased in miR122-silenced HCC cells, with increased expression levels of cancer-stem-cell markers and resistance to anti-cancer drug treatments. Conversely, maintenance of the miR122-silenced HCC cells in arginine-depleted culture media or the overexpression of miR122 reversed all of these features.These results suggest that arginine depletion may be a novel therapeutic approach to managing this disease.

Free Research Field

医歯薬学