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PKM2 通过 JAK/STAT3 通路促进肝癌细胞转移并抑制自噬。

PKM2 promotes cell metastasis and inhibits autophagy via the JAK/STAT3 pathway in hepatocellular carcinoma.

机构信息

Digestive Department, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, No. 100 Hong Kong Road, Jiang'an District, Wuhan, 430015, China.

出版信息

Mol Cell Biochem. 2021 May;476(5):2001-2010. doi: 10.1007/s11010-020-04041-w. Epub 2021 Jan 29.

Abstract

Pyruvate kinase M2 (PKM2) is a member of the pyruvate kinase family. It has been recently reported that PKM2 displays non-metabolic activities. Nevertheless, understanding of the role of PKM2 in hepatocellular carcinoma (HCC) is insufficient. Therefore, our study aimed at exploring the impact of PKM2 on malignant growth, autophagy as well as invasion in HCC. Expression of PKM2 in HCC specimens was examined by qRT-PCR and western blot. PKM2 knock down was generated in vitro by shRNA. Activities of malignant cells as well as downstream pathways were assessed. The MTT assay was carried out to evaluate HCC proliferation, and the FACS assay was conducted to study cell death. Elevated PKM2 levels were observed in HCC samples. Knockdown (KD) of PKM2 triggered apoptosis as well as autophagy and inhibited migration and proliferation of HCC cells. Furthermore, PKM2 KD reinforced JAK/STAT3 pathway stimulation. STAT3 inhibition counteracted the impact of PKM2 on proliferation, autophagy, migration as well as cell death in HCC. To conclude, the findings of our research suggest that PKM2 reinforced metastasis and inhibited autophagy in HCC through the JAK/STAT3 pathway, and that PKM2 could serve as a promising target for HCC treatment.

摘要

丙酮酸激酶 M2(PKM2)是丙酮酸激酶家族的一员。最近有报道称,PKM2 具有非代谢活性。然而,对 PKM2 在肝细胞癌(HCC)中的作用的理解还不够充分。因此,我们的研究旨在探讨 PKM2 对 HCC 中恶性生长、自噬和侵袭的影响。通过 qRT-PCR 和 Western blot 检测 HCC 标本中 PKM2 的表达。通过 shRNA 体外敲低 PKM2。评估恶性细胞的活性及下游通路。通过 MTT 检测评估 HCC 的增殖,通过 FACS 检测研究细胞死亡。在 HCC 样本中观察到 PKM2 水平升高。敲低(KD)PKM2 可触发 HCC 细胞凋亡和自噬,并抑制迁移和增殖。此外,PKM2 KD 增强了 JAK/STAT3 通路的刺激。STAT3 抑制可逆转 PKM2 对 HCC 中增殖、自噬、迁移和细胞死亡的影响。总之,我们的研究结果表明,PKM2 通过 JAK/STAT3 通路增强了 HCC 的转移并抑制了自噬,PKM2 可能成为 HCC 治疗的有前途的靶点。

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