LRIG2 regulates cell proliferation, migration and apoptosis of osteosarcoma

Abstract

Background Osteosarcoma (OS) is one of the malignant bone tumors with strong aggressiveness and poor prognosis. Leucine-rich repeats and immunoglobulin-like domains2 (LRIG2) is closely associated with the poor prognosis of a variety of tumors, but the role of LRIG2 in osteosarcoma and the underlying molecular mechanism remains unclear. Objective The aim of this study was to determine the function of LRIG2 in OS and the related molecular mechanism on cell proliferation, apoptosis and migration of OS. Methods The mRNA and protein expression of LRIG2 in OS tissues and cells was detected by qRT-PCR, western blot (WB) assay and immunohistochemistry (IHC). The cell counting Kit-8 (CCK-8), clone formation, transwell, TdT-mediated dUTP Nick-End Labeling (TUNEL) and WB assay were applied to determine the proliferation, migration and apoptosis abilities of OS cells and its molecular mechanisms. Spontaneous metastasis xenografts were established to confirm the role of LRIG2 in vivo. Results LRIG2 exhibited high expression in OS tissues and OS cell lines and the expression of which was significantly correlated with Enneking stage of patients, knockdown LRIG2 expression significantly inhibited OS cell proliferation, migration and enhanced apoptosis. Silencing LRIG2 also suppressed the growth of subcutaneous transplanted tumor in nude mice. Further, the mechanism investigation revealed that the protein level of cell proapoptotic proteins (Bax, caspase9 and caspase3) all increased attributed to LRIG2 deficiency, whereas expression of anti-apoptotic protein BCL2 decreased. LRIG2 silencing led to the decrease phosphorylation of AKT signaling, a decrease expression of vimentin and N-cadherin. Additionally, silencing LRIG2 significantly decreased the rate of tumor growth and tumor size. Conclusions LRIG2 acts as an oncogene in osteosarcoma, and it might become a novel target in the treatment of human OS.

Expression of E-cadherin and N-cadherin in Epithelial-to-Mesenchymal Transition of Osteosarcoma: A Systematic Review

“…The bulk of the results and findings are included in Table 1 . E-cadherin is a transmembrane protein that is involved in cell-cell adhesion and plays a crucial role in the maintenance of tissue architecture and organization for the appropriate compartmentalization of basal physiological functions [ 26 ]. In the context of osteosarcoma, many studies have attempted to elucidate the relationship between the expression or function of E-cadherin and how it modulates the progression of the disease [ 35 ].…”

“…In osteosarcoma, decreased E-cadherin expression has been associated with an increase in the mesenchymal phenotype of tumor cells, which contributes to the progression of the disease [ 36 ]. Overall, the role of E-cadherin in osteosarcoma progression is complex and still not fully understood, but it is clear that decreased expression or function of E-cadherin contributes to the invasive and aggressive behavior of osteosarcoma cells [ 26 ]. Thus, E-cadherin may be a potential target in the development of novel therapeutic strategies for the treatment of osteosarcoma.…”

“…The expression of E-cadherin was closely inversely related to the expression of N-cadherin, which predicted the malignant potential and invasiveness of osteosarcoma cell lines [ 27 - 29 ]. Several studies in this article concluded that upstream modification of E-cadherin expression can determine a tumor cell line’s invasiveness and is associated with the severity of cancer and tumor cell survival [ 24 - 26 ].…”