Deoxyribonuclease 1-like 3 Inhibits Hepatocellular Carcinoma Progression by Inducing Apoptosis and Reprogramming Glucose Metabolism.
Deoxyribonuclease 1-like 3 Inhibits Hepatocellular Carcinoma Progression by Inducing Apoptosis and Reprogramming Glucose Metabolism.
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脱氧核糖核酸酶 1-like 3 通过诱导细胞凋亡和重编程葡萄糖代谢抑制肝细胞癌进展
DOI：
10.7150/ijbs.57919
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发表时间：
2022
影响因子：
9.2
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Xiao Y;Yang K;Liu P;Ma D;Lei P;Liu Q
由于缺乏针对关键生存途径的药物，HCC仍然是治疗的挑战性癌症之一。考虑到癌细胞缺乏DNA酶活性，增加自主性DNA内切酶应该是癌症治疗的合理选择。在这项研究中，我们调查了是否DNASE 1 L3，一种与细胞凋亡有关的核酸内切酶，可以抑制肝癌的进展。我们发现，在肝癌组织中，DNASE 1 L3表达下调，而其高表达与肝癌患者的良好预后呈正相关。此外，肝癌患者血清DNASE 1 L3水平低于健康人。在功能上，我们发现，DNASE 1 L3抑制肿瘤细胞的增殖，通过诱导G 0/G1细胞周期阻滞和细胞凋亡在体外。此外，DNASE 1 L3过表达抑制体内肿瘤生长。此外，我们发现，DNASE 1 L3过表达通过使参与PTPN 2-HK 2和CEBPβ-p53-PFK 1通路的限速酶失活而减弱HCC细胞和组织中的糖酵解。最后，我们确定HBx通过上调ZNF 384的表达来抑制DNASE 1 L3的表达。总的来说，我们的研究结果表明，DNASE 1 L3可以通过诱导细胞凋亡和减弱糖酵解来抑制HCC的进展。我们认为，DNASE 1 L3可以被认为是一个有前途的预后生物标志物和治疗肝癌的目标。
HCC has remained one of the challenging cancers to treat, owing to the paucity of drugs targeting the critical survival pathways. Considering the cancer cells are deficient in DNase activity, the increase of an autonomous apoptisis endonuclease should be a reasonable choice for cancer treatment. In this study, we investigated whether DNASE1L3, an endonuclease implicated in apoptosis, could inhibit the progress of HCC. We found DNASE1L3 was down-regulated in HCC tissues, whereas its high expression was positively associated with the favorable prognosis of patients with HCC. Besides, serum DNASE1L3 levels were lower in HCC patients than in healthy individuals. Functionally, we found that DNASE1L3 inhibited the proliferation of tumor cells by inducing G0/G1 cell cycle arrest and cell apoptosis in vitro. Additionally, DNASE1L3 overexpression suppressed tumor growth in vivo. Furthermore, we found that DNASE1L3 overexpression weakened glycolysis in HCC cells and tissues via inactivating the rate-limiting enzymes involved in PTPN2-HK2 and CEBPβ-p53-PFK1 pathways. Finally, we identified the HBx to inhibit DNASE1L3 expression by up-regulating the expression of ZNF384. Collectively, our findings demonstrated that DNASE1L3 could inhibit the HCC progression through inducing cell apoptosis and weakening glycolysis. We believe DNASE1L3 could be considered as a promising prognostic biomarker and therapeutic target for HCC.
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影响因子：
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