Overexpression of KH-type splicing regulatory protein regulates proliferation, migration, and implantation ability of osteosarcoma

Abstract

Osteosarcoma is a common malignant bone tumor in children and adolescents. The current 5-year survival rate is ~60% and that seems to be reaching a plateau. In order to improve treatment outcomes of osteosarcoma, a better understanding of tumorigenesis and underlying molecular mechanisms is required for searching out possible new treatment targets. This study aimed to identify the potential proteins involving the pathogenesis of osteosarcoma using a proteomics approach. Proteins extracted from primary cell culture of osteosarcoma (n=7) and osteoblasts of cancellous bone (n=7) were studied. Using 2-DE based proteomics and LC-MS/MS analysis, we successfully determined seven differentially expressed protein spots. Four upregulated proteins and three downregulated proteins were observed in this study in which KH-type splicing regulatory protein (KSRP) was selected for further exploration. KSRP was significantly upregulated in osteosarcoma cells compared to osteoblasts using western blot assay. In addition, immunohistochemistry demonstrated that KSRP was also highly expressed in osteosarcoma tissue of independent cases from the experimental group. More importantly, KSRP silencing of osteosarcoma cell lines significantly decreased cell proliferation, migration ability, as well as implantation and growth ability in chick chorioallantoic membrane assay. Taken together, these findings demonstrate, that KSRP plays important roles in regulatory controls of osteosarcoma pathogenesis and serves as a potentially therapeutic target of osteosarcoma.

KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment

“…This study provides orthogonal evidence supporting a protumorigenic role of KHSRP in CRC, on the basis of extensive mining of multiple publicly available data sets, analysis of patient samples, and in vitro cell line models. Our results are in agreement with recent reports in osteosarcoma, 13 lung cancer, 12,54 papillary thyroid cancer, 55 and esophageal squamous cell carcinoma. 56 The IHC data provide evidence for KHSRP overexpression in the context of both primary tumor and metastasis.…”

“…11 Direct evidence for the involvement of KHSRP in cancer is accumulating. KHSRP has been implicated in the pathogenesis of small-cell lung cancer, 12 osteosarcoma, 13 and breast cancer. 14 Several distinct mechanisms have been proposed (eg, regulation of cell differentiation in P19 mouse teratocarcinoma cells 15 ; deregulation of oncosuppressive miRNAs, such as let-7a and miR-30c 16 ; or control of transforming growth factor-bedependent regulation of epithelial-to-mesenchymal transition 17 ).…”

Diverse roles of RNA‐binding proteins in cancer traits and their implications in gastrointestinal cancers

“…However, the crucial role of KHSRP in carcinogenesis was still unclear, because KHSRP has both oncogenic and tumor‐suppressive functions in a tissue‐specific manner. Several studies reported that KHSRP promotes cell proliferation in small cell lung cancer cells (Tong et al, ), and promotes cell migration ability in human liver cancer and osteosarcoma cells (Malz et al, ; Pruksakorn et al, ; Zubaidah et al, ). In contrast, J. Yang et al () showed that the KHSRP suppresses cell motility of glioblastoma cells.…”

KH-type splicing regulatory protein controls colorectal cancer cell growth and modulates the tumor microenvironment

“…Furthermore, KHSRP is involved in the TGF-β-dependent regulation of epithelial-to-mesenchymal transition in the mammary gland 18 . Finally, KHSRP has also been implicated in the pathogenesis of small cell lung cancer 19 and osteosarcoma 20 . There is additional indirect evidence to suggest that KHSRP has pleiotropic roles in tumorigenesis, for example through regulation of lipid metabolism or mediating the cellular response to DNA damage 12 .…”