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. 2024 Oct 30;21(10):880–897. doi: 10.20892/j.issn.2095-3941.2024.0231

Figure 3.

Figure 3

Dysregulated ubiquitination pathway drives osteosarcoma malignancy. Proliferation: Proliferation of osteosarcoma is regulated by intricate ubiquitination processes. UBE2O ubiquitinates L3MBTL2, bolstering NF-κβ expression and tumor growth. LAMTOR5-AS1 halts proliferation by blocking NRF2 ubiquitination, augmenting heme oxygenase-1 levels. TRIM21 reduces PDGFRβ via ubiquitination, inhibiting tumor expansion. A1BG-AS1 enhances proliferation by inhibiting miR-148a-3p and upregulating USP22, inhibiting SIRT1 ubiquitination. High E2 levels facilitate USP7-NLRP3 interaction, removing K48-linked ubiquitination, boosting NLRP3 inflammasome and proliferation. Invasion: Invasion is curbed by EPIC1-mediated MEF2D ubiquitination and degradation. TRAIP promotes Kank1 polyubiquitination, downregulating IGFBP3 and activating Akt, fostering invasion. FAM83H stabilizes β-catenin, upregulating cyclin D1, vimentin, and snail, promoting invasion. HDAC4 overexpression elevates PCNA while decreasing ubiquitinated PCNA, enhancing invasion. miR-140 or USP22 knockdown triggers LSD1 ubiquitination and degradation, inhibiting invasion. Migration: KEAP1-259aa interacts with ARIH1 to promote the proteasomal degradation of cytoplasmic vimentin, inhibiting osteosarcoma cell migration. CircRNA_0002669 promotes osteosarcoma cell migration by preventing MYCBP ubiquitination. USP1 interacts with TAZ, activating the Hippo signaling pathway and promoting cell migration. CHPF inhibits SKP2 ubiquitination and activates the Akt signaling pathway, promoting osteosarcoma migration. RNF180 ubiquitinates Cbx4, upregulating KLF6 and downregulating Runx2, inhibiting cell migration. Metastasis: S100A11 interacts with USP9X to stimulate the JAK2/STAT3 signaling pathway, promoting lung metastasis in osteosarcoma patients. USP5 deubiquitinates GLI1, activating the Hedgehog signaling pathway and promoting osteosarcoma metastasis. ALKBH5 increases the expression of USP22 and RNF40, inhibiting histone H2A single ubiquitination. RNF40, ubiquitinated on H2B, inhibits H2A ubiquitination in tumors, interacting with the DDB1-CUL4-based ubiquitin E3 ligase complex to promote osteosarcoma metastasis. CDK7 inhibits TRIM21-mediated GRP78 ubiquitination, and promoting osteosarcoma metastasis. miR-137 can inhibit osteosarcoma metastasis by targeting LAPTM4B to stabilize RhoA protein. Apoptosis: POLE2 enhances CD44 expression by inhibiting MDM2-mediated ubiquitination, subsequently activating the RAC signaling pathway to promote osteosarcoma cell apoptosis. TRIM22 inhibits osteosarcoma progression through Nrf2-mediated (ROS) imbalance. The p27 Thr187Ala knock-in mutation disrupts SCFSkp2 E3 ligase-mediated p27 ubiquitination, leading to p27 Thr187Ala accumulation and promoting osteosarcoma cell apoptosis. TRIM46 interacts with PPAR, ubiquitinates PPAR, activates the NF-κβ signaling pathway, and induces apoptosis.