title: Combining microRNA-449a/b with a HDAC inhibitor has a synergistic effect on growth arrest in lung cancer.
abstract: Histone deacetylases (HDACs) play a crucial role in tumorigenesis. Over-expression of HDACs has been reported in lung cancer. The mechanism of highly expressed HDAC1 in lung cancer has yet not been determined. In the present study, we showed that miR-449a/b regulates HDAC1 by directly binding with the 3' untranslated region of the HDAC1. The expression of miR-449a/b was down-regulated and the expression of HDAC1 was up-regulated in primary lung cancer. The down expression of miR-449a/b might be one mechanism for over-expression of HDAC1 in lung cancer. miR-449a/b inhibited cell growth and anchorage-independent growth. Furthermore, co-treatment with miR-449a and HDAC inhibitors had a significant growth reduction compared with HDAC inhibitor mono-treatment. These results suggest that miR-449a/b may have a tumor suppressor function and might be a potential therapeutic candidate in patients with primary lung cancer.
authors.affiliation: Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Hyo Sung
authors.initials: HS
authors.lastname: Jeon
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Lee
authors.forename: Seong Cheol
authors.initials: SC
authors.lastname: Yun
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Cha
authors.forename: Eugene
authors.initials: E
authors.lastname: Choi
authors.forename: Moon Jun
authors.initials: MJ
authors.lastname: Na
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Jaeku
authors.initials: J
authors.lastname: Kang
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Son
mesh_terms: D020413:3' Untranslated Regions / Q000187:drug effects; D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D006131:Growth Inhibitors / Q000494:pharmacology*; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011485:Protein Binding / Q000187:drug effects; D014410:Tumor Stem Cell Assay / Q000379:methods
chemical_list: D020413:3' Untranslated Regions; D006131:Growth Inhibitors; D056572:Histone Deacetylase Inhibitors; C544530:MIRN449 microRNA, human; D035683:MicroRNAs; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1