The role of programmed cell death in osteosarcoma: From pathogenesis to therapy.

Osteosarcoma (OS) is a prevalent bone solid malignancy that primarily affects adolescents, particularly boys aged 14-19. This aggressive form of cancer often leads to deadly lung cancer due to its high migration ability. Experimental evidence suggests that programmed cell death (PCD) plays a crucial role in the development of osteosarcoma. Various forms of PCD, including apoptosis, ferroptosis, autophagy, necroptosis, and pyroptosis, contribute significantly to the progression of osteosarcoma. Additionally, different signaling pathways such as STAT3/c-Myc signal pathway, JNK signl pathway, PI3k/AKT/mTOR signal pathway, WNT/ß-catenin signal pathway, and RhoA signal pathway can influence the development of osteosarcoma by regulating PCD in osteosarcoma cell. Therefore, targeting PCD and the associated signaling pathways could offer a promising therapeutic approach for treating osteosarcoma.

hsa_circ_0000006 induces tumorigenesis through miR-361-3p targeting immunoglobulin-like domains protein 1 (LRIG1) in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is considered to be the most highly prevalent bone tumor. In the progression of different human cancers, the role of circular RNAs (circRNAs) has been extensively studied. Microarray analysis has indicated that hsa_circ_0000006 expression was lower in OS, but the mechanism of hsa_circ_0000006 in regulating the progression of OS remains elusive. METHODS: The expression of cancer-related genes at the transcriptional and translational levels was assessed by RT-qPCR and western blotting (WB). Colony formation and Cell Counting Kit-8 (CCK-8) assays were used to evaluate the proliferative potential of cells. The transwell assay was used to examine the invasive and migratory potential of cells. Furthermore, dual-luciferase reporter (DLR) and RNA pull-down assays were performed for the validation of the targeting sites of hsa_circ_0000006, miR-361-3p, and the 3'-untranslated region (3'-UTR) of immunoglobulin-like domains protein 1 (LRIG1) mRNA. Moreover, the protein levels of epithelial-to-mesenchymal transition (EMT) markers were analyzed by WB. RESULTS: The expression of hsa_circ_0000006 and LRIG1 were found to be down-regulated in OS tissues and cells, while miR-361-3p was up-regulated. Knockdown of hsa_circ_0000006 promoted the progression and development of OS, as well as EMT. Furthermore, hsa_circ_0000006 was revealed as a sponge of miR-361-3p, which negatively regulates miR-361-3p expression. LRIG1 was found to be an miR-361-3p target. In OS cells, the LRIG1 expression level was decreased, with elevated expression of miR-361-3p. Advanced studies demonstrated that hsa_circ_0000006 regulates LRIG1 expression through sponging miR-361-3p, then promotes the tumorigenesis of OS. CONCLUSIONS: hsa_circ_0000006 is associated with the progression and development of OS through miR-361-3p by target LRIG1, which is a significant biomarker and effective therapeutic target for patients with OS.