在核苷（酸）类似物治疗后，慢性乙型肝炎中miRNA的失调与肝

StephenW

Cancer Lett. 2018 Jul 16. pii: S0304-3835(18)30477-4. doi: 10.1016/j.canlet.2018.07.019. [Epub ahead of print]
Dysregulation of miRNA in chronic hepatitis B is associated with hepatocellular carcinoma risk after nucleos(t)ide analogue treatment.
Wakasugi H1, Takahashi H2, Niinuma T3, Kitajima H3, Oikawa R4, Matsumoto N5, Takeba Y5, Otsubo T6, Takagi M7, Ariizumi Y7, Suzuki M8, Okuse C8, Iwabuchi S9, Nakano M10, Akutsu N11, Kang JH12, Matsui T12, Yamada N13, Sasaki H11, Yamamoto E1, Kai M3, Sasaki Y14, Sasaki S11, Tanaka Y15, Yotsuyanagi H16, Tsutsumi T17, Yamamoto H4, Tokino T14, Nakase H11, Suzuki H18, Itoh F4.
Author information

1
    Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan; Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
2
    Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan; Division of Gastroenterology, Department of Internal Medicine, St. Marianna University School of Medicine Yokohama City Seibu Hospital, Yokohama, Japan.
3
    Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
4
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
5
    Department of Pharmacology, St. Marianna University School of Medicine, Kawasaki, Japan.
6
    Department of Gastroenterological and General Surgery, St. Marianna University School of Medicine, Kawasaki, Japan.
7
    Department of Pathology, St. Marianna University, Kawasaki, Japan.
8
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan; Division of Gastroenterology and Hepatology, Kawasaki Municipal Tama Hospital, Japan.
9
    Center for Hepato-Biliary-Pancreatic and Digestive Disease, Shonan Fujisawa Tokushukai Hospital, Kanagawa, Japan.
10
    Department of Pathology, Shonan Fujisawa Tokushukai Hospital, Kanagawa, Japan.
11
    Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
12
    Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
13
    Department of Internal Medicine, Center for Liver Diseases, Kiyokawa Hospital, Tokyo, Japan.
14
    Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
15
    Department of Virology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Department Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
16
    Division of Infectious Diseases and applied immunology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
17
    Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Japan.
18
    Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan. Electronic address: [email protected].

Abstract

Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). Nucleos(t)ide analogue (NA) therapy effectively reduces the incidence of HCC, but it does not completely prevent the disease. Here, we show that dysregulation of microRNAs (miRNAs) is involved in post-NA HCC development. We divided chronic hepatitis B (CHB) patients who received NA therapy into two groups: 1) those who did not develop HCC during the follow-up period after NA therapy (no-HCC group) and 2) those who did (HCC group). miRNA expression profiles were significantly altered in CHB tissues as compared to normal liver, and the HCC group showed greater alteration than the no-HCC group. NA treatment restored the miRNA expression profiles to near-normal in the no-HCC group, but it was less effective in the HCC group. A number of miRNAs implicated in HCC, including miR-101, miR-140, miR-152, miR-199a-3p, and let-7g, were downregulated in CHB. Moreover, we identified CDK7 and TACC2 as novel target genes of miR-199a-3p. Our results suggest that altered miRNA expression in CHB contributes to HCC development, and that improvement of miRNA expression after NA treatment is associated with reduced HCC risk.
KEYWORDS:

CDK7; HBV; TACC2; miR-199a-3p; post-NA HCC

PMID:
    30026054
DOI:
    10.1016/j.canlet.2018.07.019

StephenW

巨蟹座Lett。 2018年7月16日.pii：S0304-3835（18）30477-4。 doi：10.1016 / j.canlet.2018.07.019。 [提前打印]
在核苷（酸）类似物治疗后，慢性乙型肝炎中miRNA的失调与肝细胞癌风险相关。
Wakasugi H1，Takahashi H2，Niinuma T3，Kitajima H3，Oikawa R4，Matsumoto N5，Takeba Y5，Otsubo T6，Takagi M7，Ariizumi Y7，Suzuki M8，Okuse C8，Iwabuchi S9，Nakano M10，Akutsu N11，Kang JH12，Matsui T12 ，Yamada N13，Sasaki H11，Yamamoto E1，Kai M3，Sasaki Y14，Sasaki S11，Tanaka Y15，Yotsuyanagi H16，Tsutsumi T17，Yamamoto H4，Tokino T14，Nakase H11，Suzuki H18，Itoh F4。
作者信息

1
    日本札幌市札幌医科大学医学院消化内科和肝病学系;日本札幌市札幌医科大学医学部分子生物学系。
2
    日本札幌市札幌医科大学医学部分子生物学系;日本川崎市圣玛丽安娜大学医学院内科，消化内科和肝病科;圣玛丽安娜大学医学院内科，消化内科，横滨市西武医院，日本横滨。
3
    日本札幌市札幌医科大学医学部分子生物学系。
4
    日本川崎市圣玛丽安娜大学医学院内科，消化内科和肝病学系。
五
    日本川崎市圣玛丽安娜大学医学院药理学系。
6
    日本川崎市圣玛丽安娜大学医学院消化内科和普外科。
7
    日本川崎市圣玛丽安娜大学病理学系。
8
    日本川崎市圣玛丽安娜大学医学院内科，消化内科和肝病科;日本川崎市多摩医院消化内科和肝病科。
9
    日本神奈川县Shonan Fujisawa Tokushukai医院的肝胆胰和消化系疾病中心。
10
    日本神奈川县湘南藤泽Tokushukai医院病理科
11
    日本札幌市札幌医科大学医学院消化内科和肝病学系。
12
    日本札幌市Teine Keijinkai医院消化内科。
13
    日本东京清川医院肝病中心内科
14
    日本札幌市札幌医科大学医学院边境医学研究所医学基因组科学系。
15
    日本名古屋市名古屋市立大学医学研究科病毒学系;日本名古屋市名古屋市立大学医学研究科肝脏科
16
    日本东京大学医学研究所研究医院传染病与应用免疫学研究室。
17
    日本东京大学医学研究所高级临床研究中心传染病科
18
    日本札幌市札幌医科大学医学部分子生物学系。电子地址：[email protected]。

抽象

乙型肝炎病毒（HBV）感染是肝细胞癌（HCC）的主要原因。 Nucleos（t）ide类似物（NA）疗法有效地降低了HCC的发病率，但它并不能完全预防该疾病。在这里，我们显示微小RNA（miRNA）的失调涉及NA后HCC发展。我们将接受NA治疗的慢性乙型肝炎（CHB）患者分为两组：1）NA治疗后无随访期间未发生HCC的患者（无HCC组）和2）患者（HCC组） 。与正常肝脏相比，CHB组织中miRNA表达谱显着改变，并且HCC组显示出比无HCC组更大的改变。 NA治疗使无HCC组的miRNA表达谱恢复至接近正常，但在HCC组中效果较差。涉及HCC的许多miRNA，包括miR-101，miR-140，miR-152，miR-199a-3p和let-7g，在CHB中被下调。此外，我们将CDK7和TACC2鉴定为miR-199a-3p的新靶基因。我们的结果表明，CHB中miRNA表达的改变有助于HCC的发展，NA治疗后miRNA表达的改善与HCC风险降低有关。
关键词：

CDK7; HBV; TACC2;的miR-199a的-3P;后NA HCC

结论：
    30026054
DOI：
    10.1016 / j.canlet.2018.07.019