瘦素受体（LEPR）通过调节膜联蛋白A7（ANXA7）促进肝细胞癌的增殖、迁移和侵袭，并抑制其凋亡。
Leptin Receptor (LEPR) promotes proliferation, migration, and invasion and inhibits apoptosis in hepatocellular carcinoma by regulating ANXA7.
作者信息
Huang He, Zhang Jun, Ling Fei, Huang Yuhong, Yang Min, Zhang Yao, Wei Yuanyi, Zhang Qingqing, Wang Honghai, Song Lin, Wu Ying, Yang Jiayu, Tang Jianwu
机构信息
Department of Pathology, College of Basic Medical Sciences, Dalian Medical University, 9 W. Lushun South Road, Dalian, 116044, Liaoning, China.
Department of Pathology, Tangshan People's Hospital, 65 Shengli Road, Tangshan, 063001, Hebei, China.
出版信息
Cancer Cell Int. 2021 Jan 4;21(1):4. doi: 10.1186/s12935-020-01641-w.
BACKGROUND
Leptin Receptor (LEPR) has been suggested to have several roles in cancer metastasis. However, the role of LEPR and its underlying mechanisms in lymphatic metastasis of hepatocarcinoma have not yet been studied.
METHODS
We performed bioinformatics analysis, qRT-PCR, western blotting, immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent, coimmunoprecipitation assays and a series of functional assays to investigate the roles of LEPR in hepatocellular carcinoma.
RESULTS
We discovered that LEPR was highly expressed in liver cancer tissues, and the expression of LEPR in Hca-F cells was higher than that in Hca-P cells. Furthermore, LEPR promotes the proliferation, migration and invasion and inhibits the apoptosis of hepatocarcinoma lymphatic metastatic cells. Further studies indicated that LEPR interacts with ANXA7. Mechanistically, LEPR regulated ERK1/2 and JAK2/STAT3 expression via ANXA7 regulation.
CONCLUSIONS
These findings unveiled a previously unappreciated role of LEPR in the regulation of lymphatic metastatic hepatocellular carcinoma, assigning ANXA7-LEPR as a promising therapeutic target for liver cancer treatments.
背景
瘦素受体（LEPR）在癌症转移中被认为具有多种作用。然而，LEPR在肝癌淋巴转移中的作用及其潜在机制尚未得到研究。
方法
我们进行了生物信息学分析、qRT-PCR、蛋白质免疫印迹、免疫组织化学、免疫荧光、酶联免疫吸附测定、免疫共沉淀测定以及一系列功能测定，以研究LEPR在肝细胞癌中的作用。
结果
我们发现LEPR在肝癌组织中高表达，且LEPR在Hca-F细胞中的表达高于Hca-P细胞。此外，LEPR促进肝癌淋巴转移细胞的增殖、迁移和侵袭，并抑制其凋亡。进一步研究表明，LEPR与膜联蛋白A7（ANXA7）相互作用。机制上，LEPR通过调节ANXA7来调控ERK1/2和JAK2/STAT3的表达。
结论
这些发现揭示了LEPR在调控淋巴转移型肝细胞癌中一个此前未被认识的作用，确定ANXA7-LEPR为肝癌治疗中一个有前景的治疗靶点。
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