Downregulation of 14-3-3β inhibits proliferation and migration in osteosarcoma cells

Abstract

The 14-3-3 protein isoform β (14‑3‑3β), which is an intracellular adaptor protein that exists in all eukaryotic organisms, is highly expressed in many cancer tissues, including glioma, lung carcinoma and breast cancer. However, 14‑3‑3β expression and function in osteosarcoma progression remain unknown. In the present study, the endogenous expression of 14‑3‑3β was assessed in osteosarcoma samples and the effect of 14‑3‑3β knockdown was examined in human osteosarcoma MG63 cells using small interfering RNA (siRNA). mRNA and protein expression levels for 14‑3‑3β were detected by reverse transcription‑quantitative polymerase reaction and western blotting, respectively. The results demonstrated that endogenous 14‑3‑3β mRNA and protein were highly expressed in human osteosarcoma tissues and osteosarcoma cell lines (U2OS, MG63 and SaOs‑2), but not in normal bone tissues or normal osteoblast hFOB1.19 cells. These data suggested that increased expression of 14‑3‑3β may be significantly associated with the development and progression of osteosarcoma. Therefore, the effect of 14‑3‑3β knockdown in MG63 cells was further examined in vitro. Knockdown of 14‑3‑3β by siRNA significantly decreased cell viability, and inhibited cell proliferation and invasion. In addition, 14‑3‑3β knockdown significantly decreased the protein expression levels of β‑catenin, cyclin D1, v‑myc avian myelocytomatosis viral oncogene homolog and matrix metallopeptidase 9 in osteosarcoma MG63 cells. These results suggested that the anticancer effects of 14‑3‑3β knockdown in MG63 cells might be mediated by the inhibition of the Wnt/β‑catenin signaling pathway. In summary, 14‑3‑3β knockdown decreased proliferation and invasion in MG63 cells, which suggests a potential therapeutic application for 14‑3‑3β as a novel target for the treatment of osteosarcoma patients.

Hypoxia Promotes Glioma Stem Cell Proliferation by Enhancing the 14-3-3β Expression via the PI3K Pathway

“…After 14-3-3 β siRNA application, survival rate of the transplanted mice was enhanced, and tumor volume and weight were decreased, which indicated that the effect of hypoxia on tumor growth was reversed by 14-3-3 β knockdown. In addition, a previous study also reported that 14-3-3 β downregulation inhibits osteosarcoma cell proliferation and migration [ 53 ]. The present study therefore hypothesized that 14-3-3 β may serve a crucial role in the hypoxia-induced tumor growth in glioma.…”

14‐3‐3 Family of Proteins: Biological Implications, Molecular Interactions, and Potential Intervention in Cancer, Virus and Neurodegeneration Disorders

“…[88] Osteosarcoma 14-3-3β isoform demonstrated significant upregulation in osteosarcoma samples. [89] Colorectal cancer (CRC) Elevated 14-3-3ζ expression in CRC (79.5%) compared with control tissues (21.9%) in immunohistochemistry (IHC).…”

“…Therefore, the overexpression of 14-3-3 proteins (except 14-3-3σ) in many cancers may be a target for therapeutic applications. For instance, the 14-3-3β siRNA knockdown has been reported to decrease the levels of cyclin D1 significantly, v-myc avian myelocytomatosis viral oncogene homologue and matrix metallopeptidase 9 (MMP-9) in osteosarcoma MG63 cancer cells [89].…”

Adenosine monophosphate activated protein kinase contributes to skeletal muscle health through the control of mitochondrial function

“…Mitochondrial biogenesis is necessary during muscle regeneration ( Wu et al, 2018 ; Niu et al, 2021 ). Under the pressure of differentiation, myoblasts require more energy to maintain cell remodeling; accordingly mitochondria are constantly splitting in cells, and mitochondrial autophagy is markedly increased ( Hardy et al, 2016 ; Bloemberg and Quadrilatero, 2019 ).…”