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DNAJA1通过miR-205-5p介导稳定EF1A1以促进肝癌细胞增殖和转移。

DNAJA1 Stabilizes EF1A1 to Promote Cell Proliferation and Metastasis of Liver Cancer Mediated by miR-205-5p.

作者信息

Yi Lizhi, He Shunhui, Cheng Zhengyu, Chen Xi, Ren Xiaoli, Bai Yang

机构信息

Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Department of Gastroenterology, People's Hospital of Leshan, Leshan, 614000 Sichuan Province, China.

出版信息

J Oncol. 2022 May 9;2022:2292481. doi: 10.1155/2022/2292481. eCollection 2022.

Abstract

Liver cancer is one of the most common and aggressive malignancies worldwide with poor prognosis. Studies on pathogenesis of liver cancer are urgently demanded to develop better treatment strategy. Here, we found that overexpression of DnaJ heat shock protein family (Hsp40) member A1 (DNAJA1) increased cell proliferation, invasion, and angiogenesis in Huh 7 and HepG2 cells, while depletion of DNAJA1 in MHCC-97H and HCC-M3 showed opposite effects. In vivo functional assays indicated that DNAJA1 promoted tumor growth and pulmonary metastasis in mice. Mechanistically, as a direct target of miR-205-5p, DNAJA1 promoted proliferation and metastasis of liver cancer cells by stabilizing eukaryotic elongation factor 1A1 (EF1A1). Moreover, DNAJA was markedly upregulated in liver cancer tissues ( < 0.05) and was significantly associated with poor prognosis. And its expression was correlated with differentiation ( < 0.001), dissemination ( < 0.001), and serum AFP ( = 0.029). The mRNA levels of miR-205-5p and DNAJA1 were negatively correlated in liver cancer. In conclusion, our study reveals that DNAJA1 acts as an oncogene in liver cancer via miR-205-5p/EF1A1 axis and might be a potential biomarker to predict the prognosis for liver cancer patients.

摘要

肝癌是全球最常见且侵袭性最强的恶性肿瘤之一,预后较差。迫切需要开展关于肝癌发病机制的研究,以制定更好的治疗策略。在此,我们发现DnaJ热休克蛋白家族(Hsp40)成员A1(DNAJA1)的过表达增加了Huh 7和HepG2细胞的增殖、侵袭及血管生成,而在MHCC - 97H和HCC - M3细胞中敲低DNAJA1则产生相反的效果。体内功能试验表明,DNAJA1促进小鼠肿瘤生长和肺转移。机制上,作为miR - 205 - 5p的直接靶点,DNAJA1通过稳定真核延伸因子1A1(EF1A1)促进肝癌细胞的增殖和转移。此外,DNAJA在肝癌组织中显著上调(<0.05),且与不良预后显著相关。其表达与分化(<0.001)、扩散(<0.001)及血清甲胎蛋白(AFP)(=0.029)相关。在肝癌中,miR - 205 - 5p和DNAJA1的mRNA水平呈负相关。总之,我们的研究揭示DNAJA1通过miR - 205 - 5p/EF1A1轴在肝癌中发挥癌基因作用,可能是预测肝癌患者预后的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a405/9110222/3f4ecce775b5/JO2022-2292481.001.jpg

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