Interfering Nuclear Protein Laminb1 Induces DNA Damage and Reduces Vemurafenib Resistance in Melanoma Cells In Vitro.

Cancers (Basel)

Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, China.

Published: December 2024

Background/objectives: Drug resistance poses a substantial clinical challenge in melanoma treatment, yet the underlying mechanism remains elusive. Here, we report the novel role of laminB1, a nuclear structure protein, in regulating the response of BRAF-mutated melanoma cells to vemurafenib.

Results: Our analysis of clinical samples and existing databases highlights the tight correlation between the laminB1 expression level and melanoma progression and prognosis. Notably, we observe that laminB1 expression is upregulated when BRAF-mutated melanoma cells develop resistance to vemurafenib. The knockdown of laminB1 substantially increases the sensitivity of melanoma cells to vemurafenib. Furthermore, we found laminB1 suppression increases cell apoptosis via the escalation of DNA damage in a vemurafenib-dose-dependent manner. Conversely, protective cell autophagy is negatively regulated by laminB1 suppression. Interestingly, this distinct regulation pattern of apoptosis and autophagy by laminB1 cooperatively promotes the response of BRAF-mutated melanoma cells to vemurafenib.

Conclusions: Our findings unveil the potential of laminB1 as both a diagnosis marker and a therapeutic target of melanoma.

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Source
http://dx.doi.org/10.3390/cancers16234060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11639818PMC

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