Knockdown of nuclear receptor binding SET domain-containing protein 1 (NSD1) inhibits proliferation and facilitates apoptosis in paclitaxel-resistant breast cancer cells via inactivating the Wnt/β-catenin signaling pathway.

Abstract

The burden of breast cancer (BC) has exacerbated over decades. Paclitaxel resistance is responsible for increasing BC treatment burden. Nuclear receptor binding SET domain-containing protein 1 (NSD1) is positively correlated with a poor prognosis in patients with BC. This study investigates the function of NSD1 in paclitaxel-resistant (PR) BC cells. The high levels of NSD1 and Wnt10b in PR BC cell lines (MCF-7/PR) or MCF-7 parental cells were determined by RT-qPCR. Western blotting was conducted to measure the levels of NSD1 protein, apoptosis-associated proteins, Wnt10b protein, H3K36me2 protein, H3K27me3 protein, and signal pathway-associated proteins in MCF-7/PR cells or MCF-7 cells or in vivo subcutaneous xenografted tumor model, and the results demonstrated that NSD1 inhibited cell apoptosis and promoted cell proliferation and tumor growth via activating Wnt/β-catenin pathway. Cell apoptosis and viability were estimated using cell counting kit-8 assays and flow cytometry. Positive correlation between NSD1 and Wnt10b was identified by chromatin immunoprecipitation assay. The distribution of β-catenin was determined by immunofluorescence assays. We conclude that NSD1 knockdown inhibits the viability and promotes the apoptosis of paclitaxel-resistant BC cells by inactivating the NSD1/H3K27me3/Wnt10b/β-catenin signaling pathway.

• Authors: Yi Chen, Xiao Li, Jin Xu, Hua Xiao, Cuiju Tang, Wei Liang, Xuedan Zhu, Yueyu Fang, Hanjin Wang, Junfeng Shi
• Journal: Bioengineered (Bioengineered) Vol. 13 Issue 2 Pg. 3526-3536 (02 2022) ISSN: 2165-5987 [Electronic] United States
• PMID: 35200072 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• beta Catenin
• Histone-Lysine N-Methyltransferase
• NSD1 protein, human
• Paclitaxel

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, genetics, metabolism, physiopathology)
• Cell Proliferation (drug effects)
• Drug Resistance, Neoplasm
• Female
• Histone-Lysine N-Methyltransferase (genetics, metabolism)
• Humans
• MCF-7 Cells
• Paclitaxel (pharmacology)
• Wnt Signaling Pathway (drug effects)
• beta Catenin (genetics, metabolism)