“…For example, TNF-α is a pleiotropic cytokine that triggers cell proliferation, cell death, or inflammation. 20 , 21 However, cytokine IL-32α suppresses colorectal cancer growth via TNFR1 signaling pathway. 22 …”
Inflammatory and autophagy-related gene P62 is highly expressed in most human tumor tissues. Herein, we demonstrate that P62 promotes human mesenchymal stem cells’ malignant transformation via the cascade of P62-tumor necrosis factor alpha (TNF-α)-CUDR-CTCF-insulin growth factor II (IGFII)-H-Ras signaling. Mechanistically, we reveal P62 enhances IGFII transcriptional activity through forming IGFII promoter-enhancer chromatin loop and increasing METTL3 occupancy on IGFII 3′ UTR and enhances H-Ras overexpression by harboring inflammation-related factors, e.g., TNFR1, CLYD, EGR1, NFκB, TLR4, and PPARγ. Furthermore, the P62 cooperates with TNF-α to promote malignant transformation of mesenchymal stem cells. These findings, for the first time, provide insight into the positive role that P62 plays in malignant transformation of mesenchymal stem cells and reveal a novel link between P62 and the inflammation factors in mesenchymal stem cells.
“…For example, TNF-α is a pleiotropic cytokine that triggers cell proliferation, cell death, or inflammation. 20 , 21 However, cytokine IL-32α suppresses colorectal cancer growth via TNFR1 signaling pathway. 22 …”
Inflammatory and autophagy-related gene P62 is highly expressed in most human tumor tissues. Herein, we demonstrate that P62 promotes human mesenchymal stem cells’ malignant transformation via the cascade of P62-tumor necrosis factor alpha (TNF-α)-CUDR-CTCF-insulin growth factor II (IGFII)-H-Ras signaling. Mechanistically, we reveal P62 enhances IGFII transcriptional activity through forming IGFII promoter-enhancer chromatin loop and increasing METTL3 occupancy on IGFII 3′ UTR and enhances H-Ras overexpression by harboring inflammation-related factors, e.g., TNFR1, CLYD, EGR1, NFκB, TLR4, and PPARγ. Furthermore, the P62 cooperates with TNF-α to promote malignant transformation of mesenchymal stem cells. These findings, for the first time, provide insight into the positive role that P62 plays in malignant transformation of mesenchymal stem cells and reveal a novel link between P62 and the inflammation factors in mesenchymal stem cells.
“…Subsequently, cyclin B1 is degraded during mitosis, particularly at the transition from metaphase to anaphase [ 43 ]. The phosphorylation of cdc2 at Tyr15 and Thr14 is known to be a critical regulatory step that inhibits cdc2 activity and causes G2/M arrest [ 44 , 45 ]. In addition to cyclin B1 and cdc2, the cyclin-dependent kinase (CDK) inhibitor p21 Waf1/Cip1 negatively modulates G2/M cell-cycle progression by binding to the cyclin-CDK complex [ 35 ].…”
Background: Placenta-specific 9 (Plac9) is a putative secreted protein that was first discovered in the context of embryogenesis. The expression pattern of Plac9 during embryogenesis, together with the results of recent reports, suggest that Plac9 may play a role in the liver development. The present study was conducted to investigate the secretory characteristics of Plac9 and its potential role in liver cell physiology. Methods: Immunofluorescence was employed to identify the subcellular distribution of Plac9. Cellular proliferative activity was analyzed by MTT assay and cell colony formation. The cell cycle distribution of Plac9 was analyzed by flow cytometry, and a functional analysis was performed using L02 cells following their stable infection with a lentivirus over-expressing Plac9. Results:
Plac9 is a novel protein that is localized to the cytoplasm and may be secreted through the classic endoplasmic reticulum-Golgi route. The overexpression of Plac9 inhibits cell growth and induces G2/M phase arrest. Conclusion: Our findings reveal a novel role for Plac9 in regulating cell growth.
“…In this way, Parkin induces G1/S cell cycle arrest and inhibits cell proliferation. Parkin also induces expression of Myt1, which phosphorylates CDK1 to inhibit CDK1 activity and cause G2/M cell cycle arrest in HeLa cells treated with TNF-α [ 44 ]. Fig.…”
The mutation of the Parkin gene is a cause of familial Parkinson’s disease. A growing body of evidence suggests that Parkin also functions as a tumor suppressor. Parkin is an ubiquitin E3 ligase, and plays important roles in a variety of cellular processes implicated in tumorigenesis, including cell cycle, cell proliferation, apoptosis, metastasis, mitophagy and metabolic reprogramming. Here we review the role and mechanism of Parkin in cancer.
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