Identification of PAFAH1B3 as Candidate Prognosis Marker and Potential Therapeutic Target for Hepatocellular Carcinoma.
Identification of PAFAH1B3 as Candidate Prognosis Marker and Potential Therapeutic Target for Hepatocellular Carcinoma.
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鉴定 PAFAH1B3 作为肝细胞癌候选预后标志物和潜在治疗靶点
DOI：
10.3389/fonc.2021.700700
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Xu W;Lu X;Liu J;Chen Q;Huang X;Huang K;Liu H;Zhu W;Zhang X
肝细胞癌（HCC）是全球癌症相关死亡的第四大原因。PAFAH1B3在多种肿瘤的发生发展中起着重要作用。然而，PAFAH1B3在HCC中的功能尚不清楚。应用TIMER、ONCOMINE、Human Protein Atlas （HPA）、GEPIA、The Cancer Genome Atlas （TCGA）、HCCDB、UALCAN和LinkedOmics数据库分析PAFAH1B3在HCC中的预后价值、共表达基因和调控网络。通过siRNA转染和PAFAH1B3 P11抑制剂验证其对HCC细胞系的抗肿瘤作用。采用qRT-PCR检测基因表达。采用细胞周期分析、细胞凋亡检测、CCK8实验和transwell实验研究PAFAH1B3下调在HCC细胞系中的作用。Western blot检测PAFAH1B3在HCC细胞代谢通路中的作用。根据数据库数据，PAFAH1B3在HCC患者中的表达显著升高。PAFAH1B3的高表达与较差的总生存期（OS）和无病生存期（DFS）相关。PAFAH1B3与年龄、性别、年级、阶段、种族和TP53突变状态显著相关。功能网络分析表明，PAFAH1B3可能通过细胞周期、细胞代谢、剪接体、RNA转运等途径参与HCC的发生。此外，PAFAH1B3 mRNA在HCC细胞系中的表达也有所增加。流式细胞术分析显示PAFAH1B3调控细胞凋亡和细胞周期。CCK8实验显示，PAFAH1B3沉默或PAFAH1B3药物抑制剂可抑制HepG2、Huh7和MHCC-97H细胞的增殖。Transwell实验结果显示，PAFAH1B3沉默也显著降低了HCC细胞的侵袭和迁移能力。此外，PAFAH1B3沉默显著下调糖酵解和脂质合成信号通路的表达。我们的研究结果表明，PAFAH1B3在HCC的进展中起着关键作用。PAFAH1B3作为HCC的预后标志物和潜在靶点具有前瞻性的临床意义。
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. PAFAH1B3 plays an important role on occurrence and development in a variety tumor. However, the function of PAFAH1B3 in HCC remains unclear. The TIMER, ONCOMINE, Human Protein Atlas (HPA), GEPIA, The Cancer Genome Atlas (TCGA), HCCDB, UALCAN and LinkedOmics database were used to analyze the prognostic value, co-expression genes and regulator networks of PAFAH1B3 in HCC. siRNA transfections and inhibitor of PAFAH1B3 P11 were used to verify the anti-tumor effect on HCC cell lines. Gene expression was detected by qRT-PCR. The functions of PAFAH1B3 downregulation in HCC cell lines were investigated using cell cycle analysis, apoptosis detection, CCK8 assay and transwell assay. Western blot was used to evaluate the role of PAFAH1B3 on metabolic pathways in HCC cells. Based on the data from databases, the expression of PAFAH1B3 was remarkably increased in HCC patients. High expression of PAFAH1B3 was associated with poorer overall survival (OS) and disease-free survival (DFS). And PAFAH1B3 was notably linked to age, sex, grade, stage, race, and TP53 mutational status. Then, the functional network analysis showed PAFAH1B3 may be involved in HCC through cell cycle, cell metabolism, spliceosome, and RNA transport. Furthermore, the mRNA expression of PAFAH1B3 was also increased in HCC cell lines. Flow cytometry analysis showed that PAFAH1B3 manipulated apoptosis and cell cycle regulation. CCK8 assay showed that PAFAH1B3 silencing or pharmacologic inhibitor of PAFAH1B3 inhibited the proliferation of HepG2, Huh7 and MHCC-97H cells. Transwell assay results showed that PAFAH1B3 silencing also significantly impaired the invasion and migratory ability of HCC cells. In addition, PAFAH1B3 silencing significantly downregulated the expression of glycolysis and lipid synthesis signaling pathways. Our findings suggested that PAFAH1B3 plays a critical role in progression of HCC. PAFAH1B3 as a prognosis marker and potential target for HCC has prospective clinical significance.
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影响因子：
6.2
作者：
Ma, Chaoqun;Huang, Shuhong;Wang, Jianming
通讯作者：
Wang, Jianming
影响因子：
4
作者：
Kohnz RA;Mulvihill MM;Chang JW;Hsu KL;Sorrentino A;Cravatt BF;Bandyopadhyay S;Goga A;Nomura DK
通讯作者：
Nomura DK
影响因子：
3.3
作者：
Chen, X;Cheung, ST;Brown, PO
通讯作者：
Brown, PO
DOI：
10.1002/hep.29236
发表时间：
2017-12
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Diab A;Foca A;Fusil F;Lahlali T;Jalaguier P;Amirache F;N'Guyen L;Isorce N;Cosset FL;Zoulim F;Andrisani O;Durantel D
通讯作者：
Durantel D
PAFAH1B3 的异常表达影响骨肉瘤的增殖和凋亡
影响因子：
4.7
作者：
Fan J;Yang Y;Qian JK;Zhang X;Ji JQ;Zhang L;Li SZ;Yuan F
通讯作者：
Yuan F