Identification of genes contributing to cisplatin resistance in osteosarcoma cells

Abstract

Osteosarcomas are prevalent in children and young adults and have a high recurrence rate. Cisplatin, doxorubicin, and methotrexate are common adjuvant chemotherapy drugs for treatment of osteosarcoma, but multidrug resistance is a growing problem. Therefore, understanding the molecular mechanisms of chemotherapy resistance in osteosarcoma cells is crucial for developing new therapeutic approaches and ultimately improving the prognosis of osteosarcoma patients. To identify genes associated with cisplatin resistance in osteosarcoma, we screened a large‐scale mutant library generated by transfecting human osteosarcoma cells with a piggyBac (PB) transposon‐based gene activation vector. Several candidate genes were identified by using Splinkerette‐PCR paired with Next Generation Sequencing. We created a disease‐free survival predictor model, which includes ZNF720 , REEP3 , CNNM2 , and CGREF1 , using TARGET (Therapeutically Applicable Research to Generate Effective Treatments) datasets. Additionally, the results of our enrichment analysis between the Four_genes_high group and Low_group suggested that these four genes may participate in cisplatin resistance in osteosarcoma through cross talk between various signaling pathways, especially the signaling pathway related to bone formation. These data may help guide future studies into chemotherapy for osteosarcoma.

Genome-wide Mendelian Randomization Identifies Potential Drug Targets for Dorsopathies

“…In the research of Xiang et al, the colorectal cancer patients with higher expression of CGREF1 were found to have significantly better overall survival than patients with lower expression, and the role of CGREF1 in the prognosis of Early-onset colorectal cancer was reported [33]. Furthermore, Xie et al observed that CGREF1 expression were high in the tissue of osteosarcoma patients while it were lowly expressed in normal tissue, and speculated that CGREF1 can predict drug resistance to osteosarcoma [34]. However, the biological function of CGREF1 is poorly explored, and further study for its mechanisms and roles in these diseases is warranted.…”

REEP3 is a potential diagnostic and prognostic biomarker correlated with immune infiltration in pancreatic cancer

“…REEP3 is known to play a role in adipocyte generation and differentiation 15 . Recent studies have shown that REEP3 is significantly expressed in different types of tumors, with implications for tumor invasiveness and prognosis 16 , 17 . This suggests that REEP3 could potentially enhance the migratory and invasive abilities of tumor cells by influencing cell adhesion and cytoskeletal rearrangement.…”