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DNAJ热休克蛋白家族成员C1可调节肝癌细胞的增殖和迁移。

DNAJ heat shock protein family member C1 can regulate proliferation and migration in hepatocellular carcinoma.

作者信息

Fan Yu-Chun, Meng Zhi-Yong, Zhang Chao-Sheng, Wei De-Wei, Wei Wan-Shuo, Xie Xian-Dong, Huang Ming-Lu, Jiang Li-He

机构信息

Medical College, Guangxi University, Nanning, Guangxi, China.

School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, China.

出版信息

PeerJ. 2023 Jul 26;11:e15700. doi: 10.7717/peerj.15700. eCollection 2023.

Abstract

BACKGROUND

DNAJ heat shock protein family (Hsp40) member C1(DNAJC1) is a member of the DNAJ family. Some members of the DNAJ gene family had oncogenic properties in many cancers. However, the role of DNAJC1 in hepatocellular carcinoma (HCC) was unclear.

METHODS

In this study, expression and prognostic value of DNAJC1 in HCC were analyzed by bioinformatics. Quantitative real-time PCR and Western blotting were used to verify DNAJC1 expression in liver cancer cell lines. Furthermore, immunohistochemical (IHC) was used to detect DNAJC1 expression in liver cancer tissues. Subsequently, the effect of DNAJC1 on the proliferation, migration, invasion and apoptosis of HCC cells was detected by knocking down DNAJC1. Finally, gene set enrichment analysis (GSEA) was used to investigate the potential mechanism of DNAJC1 and was verified by Western blotting.

RESULTS

DNAJC1 was highly expressed in HCC and was significantly associated with the prognosis of patients with HCC. Importantly, the proliferation, migration and invasion of Huh7 and MHCC97H cells were inhibited by the knockdown of DNAJC1 and the knockdown of DNAJC1 promoted Huh7 and MHCC97H cell apoptosis. Furthermore, compared to the negative control group, DNAJC1 knockdown in Huh7 and MHCC97H cells promoted the expression of p21, p53, p-p53(Ser20), Bax and E-cadherin proteins, while inhibiting the expression of PARP, MMP9, Vimentin, Snai1, Bcl-2 and N-cadherin proteins.

CONCLUSIONS

DNAJC1 had a predictive value for the prognosis of HCC. Knockdown of DNAJC1 may inhibit HCC cell proliferation, migration and invasion and promote the HCC cell apoptosis through p53 and EMT signaling pathways.

摘要

背景

DNAJ热休克蛋白家族(Hsp40)成员C1(DNAJC1)是DNAJ家族的一员。DNAJ基因家族的一些成员在许多癌症中具有致癌特性。然而,DNAJC1在肝细胞癌(HCC)中的作用尚不清楚。

方法

在本研究中,通过生物信息学分析DNAJC1在HCC中的表达及预后价值。采用定量实时PCR和蛋白质印迹法验证DNAJC1在肝癌细胞系中的表达。此外,采用免疫组织化学(IHC)检测肝癌组织中DNAJC1的表达。随后,通过敲低DNAJC1检测其对HCC细胞增殖、迁移、侵袭和凋亡的影响。最后,采用基因集富集分析(GSEA)研究DNAJC1的潜在机制,并通过蛋白质印迹法进行验证。

结果

DNAJC1在HCC中高表达,且与HCC患者的预后显著相关。重要的是,敲低DNAJC1可抑制Huh7和MHCC97H细胞的增殖、迁移和侵袭,且敲低DNAJC1可促进Huh7和MHCC97H细胞凋亡。此外,与阴性对照组相比,敲低Huh7和MHCC97H细胞中的DNAJC1可促进p21、p53、p-p53(Ser20)、Bax和E-钙黏蛋白的表达,同时抑制PARP、MMP9、波形蛋白、Snail1、Bcl-2和N-钙黏蛋白的表达。

结论

DNAJC1对HCC的预后具有预测价值。敲低DNAJC1可能通过p53和EMT信号通路抑制HCC细胞的增殖、迁移和侵袭,并促进HCC细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61c/10386825/6262526746f5/peerj-11-15700-g001.jpg

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