LIMS2 is Downregulated in Osteosarcoma and Inhibits Cell Growth and Migration

Abstract

Background/objective. LIM and LIM zinc finger domain containing 2 (LIMS2) is one of the two members of LIMS family, which plays crucial roles in regulating cell-extracellular matrix adhesion and cell motility. Here, we explored the expression and methylation levels of LIMS2 in osteosarcoma (OS) and the role of LIMS2 in OS progression. Methods. GEO, GEPIA, and UALCAN databases were used to assess LIMS2 expression in OS. UALCAN and CCLE databases were applied to assess the methylation levels of LIMS2 in OS tissues and cells, which was verified in OS cells using the methylation specific PCR. The effects of LIMS2 on regulating OS cell growth, migration and invasion were determined by CCK-8, Edu staining, and transwell chambers, respectively. The role of LIMS2 in the activation of MAPK signaling was assessed using western blotting assay in OS cells. Results. LIMS2 expression was declined in OS tissues and cells, while its methylation level was increased. The low expression of LIMS2 was associated with shorter overall survival and disease-free survival. Overexpression of LIMS2 inhibited cell growth, migration, and invasion and decreased the levels of p-ERK/ERK, p-P38/P38, and p-JNK/JNK. Conclusion. LIMS2 expression was decreased in OS, which was associated with hypermethylation level and poor prognosis. LIMS2 overexpression inhibited OS cell growth and migration, which may be caused by the suppression of MAPK signaling.

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma—A Narrative Review

“…Another pivotal conduit is the C-Jun-MMP9/Bcl-2 pathway. Activation of the MAPK family of serine/threonine kinases leads to the phosphorylation of multiple substrates, pivotal for cell proliferation, differentiation, and migration [ 45 , 46 ]. In particular, the activation of c-Jun augments MMP9 and Bcl-2 expressions, bolstering the tumor’s proliferation and metastatic potential [ 47 ].…”

Molecular mechanisms of osteosarcoma metastasis and possible treatment opportunities

“…As upstream signaling agents of MMPs, mitogen-activated protein kinase (MAPK) is a family of serine/threonine kinases that includes extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) 1/2, and p38. Activation of MAPK is followed by the phosphorylation of various cytosolic substrates that participate in numerous cellular activities such as cell proliferation, differentiation, invasion, migration, and death ( 43 , 44 ).…”