title: Baicalein, a Natural Anti-Cancer Compound, Alters MicroRNA Expression Profiles in Bel-7402 Human Hepatocellular Carcinoma Cells.
abstract: OBJECTIVE
  Baicalein has been shown to possess significant anti-hepatoma activity by inhibiting cell proliferation. Whether the anti-proliferative effect of baicalein is related to its modulation of miRNA expression in hepatocellular carcinoma (HCC) is still unknown.
  
  
  METHODS
  The anti-proliferative effects of baicalein on HCC cell line Bel-7402 was assessed by detecting the proliferation activity, cell cycle distribution, expression changes of p21/CDKN1A, P27/CDKN1B, total Akt and phosphoryted AKT. Microarray analysis was conducted to determine the miRNA expression profiles in baicalein-treated or untreated Bel-7402 cells and then validated by qRT-PCR in two HCC cell lines (Bel-7402 and Hep3B). The gain-of-function of miR-3127-5p was performed by detecting anti-proliferative effects after transfecting miRNA mimics in cells. Finally, the expression level of miR-3127-5p in different HCC cell lines was determined by qRT-PCR.
  
  
  RESULTS
  Baicalein was able to inhibit the proliferation of Bel-7402 cells by inducing cell cycle arrest at the S and G2/M phase via up-regulating the expression of p21/CDKN1A and P27/CDKN1B and suppressing the PI3K/Akt pathway. Baicalein could alter the miRNA expression profiles in Bel-7402 cells. Putative target genes for differentially expressed miRNAs could be enriched in terms of cell proliferation regulation, cell cycle arrest and were mainly involved in MAPK, PI3K-Akt, Wnt, Hippo and mTOR signaling pathways. MiR- 3127-5p, one of up-regulated miRNAs, exhibits low expression level in several HCC cell lines and its overexpression could inhibit cell growth of Bel-7402 and Hep3B cell lines by inducing S phase arrest by up-regulating the expression of p21and P27 and repressing the PI3K/Akt pathway.
  
  
  CONCLUSIONS
  Modulation of miRNA expression may be an important mechanism underlying the anti-hepatoma effects of baicalein.
authors.affiliation: National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the second affiliated hospital, Xi' an Jiaotong University, Xi'an, China.|Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, Shaanxi, Xi'an, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Bie
authors.affiliation: National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the second affiliated hospital, Xi' an Jiaotong University, Xi'an, China.|Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, Shaanxi, Xi'an, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the second affiliated hospital, Xi' an Jiaotong University, Xi'an, China.|Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, Shaanxi, Xi'an, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the second affiliated hospital, Xi' an Jiaotong University, Xi'an, China.|Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, Shaanxi, Xi'an, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the second affiliated hospital, Xi' an Jiaotong University, Xi'an, China.|Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, Shaanxi, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, Shaanxi, Xi'an, China.|Key Laboratory of Environment and Disease-Related Gene, Ministry of Education, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.affiliation: National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the second affiliated hospital, Xi' an Jiaotong University, Xi'an, China.|Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, Shaanxi, Xi'an, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the second affiliated hospital, Xi' an Jiaotong University, Xi'an, China.|Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, Shaanxi, Xi'an, China.|Key Laboratory of Environment and Disease-Related Gene, Ministry of Education, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Zongfang
authors.initials: Z
authors.lastname: Li
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D044950:Flavanones; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D035683:MicroRNAs / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; C000605234:MIRN3127 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C006680:baicalein
keywords: Anti-proliferative; Baicalein; Expression profiling; Hepatocellular carcinoma; MicroRNA