Autophagy and apoptosis-related genes in chronic liver disease and hepatocellular carcinoma.
Autophagy and apoptosis-related genes in chronic liver disease and hepatocellular carcinoma.
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DOI：
10.1186/1471-230x-12-118
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发表时间：
2012-08-28
影响因子：
2.4
通讯作者：
Bortolami M
中科院分区：
文献类型：
--
作者：
Kotsafti A;Farinati F;Cardin R;Cillo U;Nitti D;Bortolami M
自噬的失调在包括癌症在内的许多疾病的发病机制中是重要的。然而，自噬的生物学作用的几个方面仍然不清楚，细胞凋亡和自噬之间的关系，特别是在肝脏中的关系还有待深入研究。在这项研究中，我们评估了Beclin 1（一种主要的自噬剂，它桥接自噬，凋亡和分化），以及促凋亡（Bad，Bax）和抗凋亡（Bcl-2，Bcl-xL）因子在不同阶段肝病患者肝脏样本中的表达。该研究涉及93例患者，包括49例慢性肝炎（CH）（30例HCV和19例HBV相关）、13例肝硬化（CIRR）（10例HCV和3例HBV相关）、21例肝细胞癌（HCC和瘤周组织[PHCC]）和10例对照（CONTR）。采用实时荧光定量PCR和蛋白质印迹法检测mRNA和蛋白质表达水平。HCC中Beclin 1 mRNA水平低于CH（P = 0.010）或CIRR（P = 0.011），Bcl-xL转录水平也低于CH（P < 0.0001）。Bad mRNA水平在CH和CIRR中高于对照组，而Bax转录本在所有组织中均增加（P = 0.036）。PHCC表达Bcl-2 mRNA水平最高。HBV相关CH组织中Bcl-xL和Bad mRNA水平显著高于HCV相关CH组织（P = 0.003和P = 0.016）。CH和CIRR组织中Beclin 1、Bcl-xL和Bad水平较高，表明病毒性肝炎早期和中期自噬和细胞凋亡之间存在相互作用。在HCC中，这些过程似乎下调，可能使肿瘤肝细胞的存活和生长。
Dysregulation of autophagy is important in the pathogenesis of many diseases, including cancer. Several aspects of the biological role of autophagy are however still unclear and the relationship between apoptosis and autophagy, particularly in the liver has yet to be thoroughly explored. In this study we evaluated the expression of Beclin 1 (one of the main autophagocytic agents, which bridges autophagy, apoptosis and both differentiation), and both pro- (Bad, Bax) and anti-apoptotic (Bcl-2, Bcl-xL) factors in liver samples from patients with different stages of liver disease. The study concerned 93 patients from 49 cases of chronic hepatitis (CH) (30 HCV and 19 HBV-related), 13 of cirrhosis (CIRR) (10 HCV and 3 HBV-related), 21 of hepatocellular carcinoma (both HCC and peritumoral tissues [PHCC]), and 10 controls (CONTR). Real-time PCR and Western blotting were used to measure mRNA and protein expression levels. Beclin 1 mRNA levels were lower in HCC than in CH (P = 0.010) or CIRR (P = 0.011), and so were the Bcl-xL transcripts (P < 0.0001). Bad mRNA levels were higher in CH and CIRR than in CONTR, while Bax transcripts were increased in all tissues (P = 0.036). PHCC expressed the highest Bcl-2 mRNA levels. HBV-related CH tissues showed significantly higher Bcl-xL and Bad mRNA levels than HCV-related CH (P = 0.003 and P = 0.016, respectively). High Beclin 1, Bcl-xL and Bad levels in CH and CIRR tissues suggest an interaction between autophagy and apoptosis in the early and intermediate stages of viral hepatitis. In HCC these processes seem to be downregulated, probably enabling the survival and growth of neoplastic hepatocytes.