Abstract
BackgroundLeptin 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.MethodsWe 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.ResultsWe 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.ConclusionsThese 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.
Highlights
Leptin Receptor (LEPR) has been suggested to have several roles in cancer metastasis
We explored whether LEPR promotes proliferation, migration, and invasion and inhibits apoptosis in hepatocellular carcinoma by regulating Annexin A7 (ANXA7)
The cells were divided into six groups: shRNA-LEPR plasmids were transfected into Hca-F cells (FLEPR−DOWN cells); plasmids containing a sequence unrelated to LEPR were transfected into Hca-F cells (FLEPR−NC cells); ANXA7 plasmids were transfected into Hca-P cells (PANXA7− UP cells); plasmids containing a sequence unrelated to ANXA7 were transfected into Hca-F cells (FANXA7−NC cells); plasmids containing a sequence unrelated to ANXA7 were transfected into Hca-P cells (PANXA7−NC cells), and shRNA-ANXA7 plasmids were transfected into Hca-F cells (FANXA7−DOWN cells)
Summary
Leptin Receptor (LEPR) has been suggested to have several roles in cancer metastasis. The role of LEPR and its underlying mechanisms in lymphatic metastasis of hepatocarcinoma have not yet been studied. As the first step of the metastatic process, is an important determinant of the prognosis of hepatocellular carcinoma [3]. In-depth research exploring specific and sensitive biomarkers, lymphatic metastasis-related proteins and the molecular. The Annexin family plays important roles in cell membrane phospholipids, membrane receptor regulation, cytoskeleton activity, membrane transport and cell adhesion [4]. Studies have shown that ANXA7 has Ca2+-dependent membrane fusion activity and can promote membrane fusion, adhesion and transport [5]. Recent studies indicate that ANXA7 is abnormally expressed in a variety of tumours. The levels of ANXA7 expression in liver cancer, breast cancer nasopharyngeal cancer, gastric cancer, colorectal cancer, and cervical
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