Calponin 3 (CNN3) promotes malignant behavior in diffuse large B-cell lymphoma (DLBCL) cells both in vivo and in vitro, according to a study published in Oncology Reports.
CNN3 is highly expressed in DLBCL cells compared to normal blood samples. In the study, CNN3 promoted the proliferation of DLBCL cells and the transition from G1/S in the cell cycle. In contrast, silencing of CNN3 had the opposite effects. Western blot analysis revealed that levels of cyclin D1, cyclin-dependent kinase (CDK) 6, CDK2, and Ser801/811 were increased by the overexpression of CNN3 but decreased when it was silenced.
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CNN3 knockdown also induced a significant increase in apoptosis in DLBCL cells, indicating that it has a potential role in inhibiting apoptosis of malignant cells. The increase was observed for both early and late apoptosis, and the apoptotic markers, cleaved caspase-3/9 and cleaved poly ADP-ribose polymerase-1 (PARP-1), were also increased.
Forkhead box O3 (FOXO3), a known tumor suppressor in DLBCL, was found to bind to the −1955/-1948 and −1190/-1183 promotor sequence sites of CNN3. Greater binding affinity was observed for the −1955/-1948 site than the −1190/-1183 site.
In DLBCL cell lines, overexpression of FOXO3 reduced the messenger RNA and protein expression of CNN3 by roughly 50%. FOXO3 overexpression also resulted in significant changes in the cell cycle distribution of the DLBCL cells and significantly increased the apoptosis rate of the cells. Overexpression of CNN3 in the DLBCL cell lines was able to reverse the changes to the cell cycle and apoptosis rate caused by the overexpression of FOXO3.
“On the whole, the present study demonstrates that CNN3, whose transcriptional activity is negatively regulated by FOXO3, contributes to the malignant behavior of DLBCL cells. The findings of the present study may provide novel diagnostic or therapeutic insight for DLBCL in clinical practice,” the study authors said.
Two different DLBCL cell lines were used during the study, including DB and SU-DHL-4. For in vivo studies, BALB/C nude mice were subcutaneously injected with DB cells overexpressing or silencing CNN3.
Reference
Xing X, Liu M, Wang X, Guo Q, Wang H. Promoting effects of calponin 3 on the growth of diffuse large B‑cell lymphoma cells. Oncol Rep. Published online January 13, 2023. doi:10.3892/or.2023.8483
