miR-579-3p Controls Hepatocellular Carcinoma Formation by Regulating the Phosphoinositide 3-Kinase-Protein Kinase B Pathway in Chronically Inflamed Liver.
miR-579-3p Controls Hepatocellular Carcinoma Formation by Regulating the Phosphoinositide 3-Kinase-Protein Kinase B Pathway in Chronically Inflamed Liver.
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DOI：
10.1002/hep4.1894
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发表时间：
2022-06
影响因子：
5.1
通讯作者：
中科院分区：
文献类型：
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慢性肝炎会导致持续的肝损伤，并伴有进行性肝纤维化和肝硬变，最终可能导致肝细胞癌(HCC)。虽然10年内发生肝癌的肝硬变患者约为20%，但这些患者中的许多人一生中都没有肿瘤。阐明慢性肝脏炎症的各种后果的机制是肝癌研究中的一个关键方面。除了多种因素外，microRNAs(MiRNAs)也被证明参与促进肝癌的发生。因此，我们想要确定参与肝细胞癌发展的miRNAs的特征，我们设计了一项纵向研究，使用来自瑞士几个病理研究所的福尔马林固定和石蜡包埋的肝活检样本。我们用nCounterNanostring技术检测了同一患者在肝癌形成前后配对的非肿瘤性肝组织中miRNA的表达。在相似的时间范围内保持无肿瘤的肝硬变患者(n=26)作为对照队列。两个队列的比较显示，发生肝癌的患者的肝组织显示miR-579-3p的下调是肝癌发生的早期步骤，这一点在验证队列中得到了进一步证实。与信使RNA表达谱的相关性进一步表明，miR-579-3p直接抑制磷脂酰肌醇-4，5-二磷酸3-激酶催化亚单位α(PIK3CA)的表达，从而抑制蛋白激酶B(AKT)和磷酸化AKT的表达。体外实验和使用簇状规则间隔短回文重复序列(CRISPR)/Cas9技术证实了miR-579-3p控制肝癌细胞系的细胞增殖和迁移。结论：肝细胞癌患者肝组织中miRNA的表达发生了变化。MIR-579-3P被认为是一种新的肿瘤抑制因子，在肝癌发生的早期调节肌醇磷脂3-激酶-AKT信号转导。
Chronic liver inflammation causes continuous liver damage with progressive liver fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma (HCC). Whereas the 10‐year incidence for HCC in patients with cirrhosis is approximately 20%, many of these patients remain tumor free for their entire lives. Clarifying the mechanisms that define the various outcomes of chronic liver inflammation is a key aspect in HCC research. In addition to a wide variety of contributing factors, microRNAs (miRNAs) have also been shown to be engaged in promoting liver cancer. Therefore, we wanted to characterize miRNAs that are involved in the development of HCC, and we designed a longitudinal study with formalin‐fixed and paraffin‐embedded liver biopsy samples from several pathology institutes from Switzerland. We examined the miRNA expression by nCounterNanostring technology in matched nontumoral liver tissue from patients developing HCC (n = 23) before and after HCC formation in the same patient. Patients with cirrhosis (n = 26) remaining tumor free within a similar time frame served as a control cohort. Comparison of the two cohorts revealed that liver tissue from patients developing HCC displayed a down‐regulation of miR‐579‐3p as an early step in HCC development, which was further confirmed in a validation cohort. Correlation with messenger RNA expression profiles further revealed that miR‐579‐3p directly attenuated phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA) expression and consequently protein kinase B (AKT) and phosphorylated AKT. In vitro experiments and the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology confirmed that miR‐579‐3p controlled cell proliferation and cell migration of liver cancer cell lines. Conclusion: Liver tissues from patients developing HCC revealed changes in miRNA expression. miR‐579‐3p was identified as a novel tumor suppressor regulating phosphoinositide 3‐kinase–AKT signaling at the early stages of HCC development.
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影响因子：
50.3
作者：
Nakagawa S;Wei L;Song WM;Higashi T;Ghoshal S;Kim RS;Bian CB;Yamada S;Sun X;Venkatesh A;Goossens N;Bain G;Lauwers GY;Koh AP;El-Abtah M;Ahmad NB;Hoshida H;Erstad DJ;Gunasekaran G;Lee Y;Yu ML;Chuang WL;Dai CY;Kobayashi M;Kumada H;Beppu T;Baba H;Mahajan M;Nair VD;Lanuti M;Villanueva A;Sangiovanni A;Iavarone M;Colombo M;Llovet JM;Subramanian A;Tager AM;Friedman SL;Baumert TF;Schwarz ME;Chung RT;Tanabe KK;Zhang B;Fuchs BC;Hoshida Y;Precision Liver Cancer Prevention Consortium
通讯作者：
Precision Liver Cancer Prevention Consortium
肝癌的发生需要通过 CD44 增强的生长因子信号传导抑制 p53
影响因子：
50.3
作者：
Dhar D;Antonucci L;Nakagawa H;Kim JY;Glitzner E;Caruso S;Shalapour S;Yang L;Valasek MA;Lee S;Minnich K;Seki E;Tuckermann J;Sibilia M;Zucman-Rossi J;Karin M
通讯作者：
Karin M
影响因子：
25.7
作者：
Fujiwara N;Friedman SL;Goossens N;Hoshida Y
通讯作者：
Hoshida Y
影响因子：
4.2
作者：
Lin, Maosong;Chen, Weichang;Shen, Xaoying
通讯作者：
Shen, Xaoying
影响因子：
29.4
作者：
SHEU, JC;SUNG, JL;LEE, CZ
通讯作者：
LEE, CZ