Journal
EXPERIMENTAL CELL RESEARCH
Volume 409, Issue 2, Pages -Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2021.112914
Keywords
CLEC12B; SHP-1; Lung cancer; Cell behavior; PI3K; AKT
Categories
Funding
- National Science and Technology Major Project for Control and Prevention of Major Infectious Diseases of China [2017ZX10103004]
- Natural Science Foundation of Heilongjiang Province [JJ2019LH1185]
- China Postdoctoral Science Foundation [2018M640309]
- Heilongjiang Province Postdoctoral Science Foundation [2018JTC]
- Top talent program Fung of Harbin Medical University Cancer Hospital [BJQN2018-06]
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CLEC12B, a C-type lectin-like receptor, is down-regulated in lung cancer, leading to increased cell proliferation and cell cycle entry, while inhibiting cell apoptosis. This process may be mediated through the PI3K/AKT signaling pathway.
Lung cancer is the leading cause of cancer mortality worldwide. CLEC12B, a C-type lectin-like receptor, is lowexpressed in lung cancer tissues. However, the function of CLEC12B in lung cancer and its underlying mechanism remain unclear. Here, an obvious down-regulation of CLEC12B was observed in lung cancer cells compared with the normal lung epithelial cells. CLEC12B over-expression suppressed cell viability and cell cycle entry in lung cancer, along with the reduction of PCNA and cyclin D1 expressions, while silencing CLEC12B possessed the opposite effects. Over-expression of CLEC12B promoted lung cancer cell apoptosis, accompanied by decreased Bcl-2 and increased Bax, cleaved caspase-3 and cleaved caspase-9. Moreover, CLEC12B decreased phosphorylation of PI3K-p85 and AKT proteins. By contrast, CLEC12B knockdown activated the PI3K/AKT pathway. In vivo, CLEC12B inhibited tumor growth in lung cancer, which can be reversed by CLEC12B inhibition. Co-IP and immunofluorescence assays confirmed the interaction between CLEC12B and SHP-1, and CLEC12B overexpression increased SHP-1 level. Furthermore, knocking down SHP-1 abrogated the above biological phenotypes caused by CLEC12B elevation. Taken together, our findings demonstrate that CLEC12B serves as a tumorsuppressing gene in lung cancer through positively regulating SHP-1 expression, which may be mediated by the PI3K/AKT signaling pathway.
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