Oncogenic Properties of Candidate Oncogenes in Chromosome Region 17p11.2p12 in Human Osteosarcoma

Abstract

Osteosarcomas are primary tumors of bone that most often develop in adolescents. They are characterized by complex genomic changes including amplifications, deletions, and translocations. The chromosome region 17p11.2p12 is frequently amplified in human high grade osteosarcomas (25% of cases), suggesting the presence of one or more oncogenes. In previous studies, we identified 9 candidate oncogenes in this region (GID4, ARGHAP44, LRRC75A-AS1, TOP3A, COPS3, SHMT1, PRPSAP2, PMP22, and RASD1). The aim of the present study was to determine their oncogenic properties. Therefore, we generated osteosarcoma cell lines overexpressing these genes, except for LRRC75A-AS1 and PRPSAP2, and subjected these to functional oncogenic assays. We found that TOP3A, SHMT1, and RASD1 overexpression provided increased proliferation and that ARGHAP44, COPS3, and PMP22 overexpression had a stimulatory effect on migration and invasion of the cells. COPS3 and PMP22 overexpression additionally improved the ability of the cells to form new colonies. No oncogenic effect could be demonstrated for GID4 overexpression. We conclude that the concerted amplification-mediated overexpression of these genes in 17p11.2p12 may contribute to the oncogenic process in malignant osteosarcoma.

Novel oncogene COPS3 interacts with Beclin1 and Raf-1 to regulate metastasis of osteosarcoma through autophagy

“…Previous studies have revealed that COPS3 promotes osteosarcoma cell migration and invasion [ 31 ], and suppression of COPS3 could inhibit growth and induce apoptosis in lung cancer and hepatocellular carcinoma [ 32 , 33 ]. However, our data clearly show that COPS3 silencing did not significantly inhibit osteosarcoma growth in vivo.…”

“…However, our data clearly show that COPS3 silencing did not significantly inhibit osteosarcoma growth in vivo. Moreover, overexpression of COPS3 did not significantly enhance cell proliferation, although its overexpression markedly increased cell migration and invasion in osteosarcoma SAOS-2 cells [ 31 ]. Therefore, we reason that COPS3 might function in a cell type-dependent manner concerning its role in the growth of cancer cells, whereas it mainly acts to promote metastasis in osteosarcoma cells.…”

Long non-coding RNA LRRC75A-AS1 facilitates triple negative breast cancer cell proliferation and invasion via functioning as a ceRNA to modulate BAALC

“…A novel lncRNA LRRC75A-AS1 (also named SNHG29) located at 17p11.2 has 892 bp in length. Previously, LRRC75A-AS1 was reported to has oncogenic properties 15 . Besides, LRRC75A-AS1 has been validated in glioblastoma, and it regulates the miR-223-3p/CTNND1 axis to promote glioblastoma through Wnt/β-catenin pathway 16 .…”

Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification

“…Among these candidates, changes in the expression level of Lrrc75a-as1 influenced calcium deposition in VSMCs. In previous studies, Lrrc75a-as1 was shown to be expressed in normal villous maturation, human osteosarcoma, breast cancer, and gastric cancer tissues 45–48 . Lrrc75a-as1 was also predicted as a prognostic factor in acute myeloid leukemia based on statistical analysis 49 .…”