High G9a Expression in DLBCL and Its Inhibition by Niclosamide to Induce Autophagy as a Therapeutic Approach

Chin Mu Hsu, Kung Chao Chang, Tzer Ming Chuang, Man Ling Chu, Pei Wen Lin, Hsiao Sheng Liu, Shih Yu Kao, Yi Chang Liu, Chien Tzu Huang, Min Hong Wang, Tsung Jang Yeh, Yuh Ching Gau, Jeng Shiun Du, Hui Ching Wang, Shih Feng Cho, Chi En Hsiao, Yuhsin Tsai, Samuel Yien Hsiao, Li Chuan Hung, Chia Hung YenHui Hua Hsiao

研究成果: Article同行評審


Background: Diffuse large B-cell lymphoma (DLBCL) is a malignant lymphoid tumor disease that is characterized by heterogeneity, but current treatment does not benefit all patients, which highlights the need to identify oncogenic genes and appropriate drugs. G9a is a histone methyltransferase that catalyzes histone H3 lysine 9 (H3K9) methylation to regulate gene function and expression in various cancers. Methods: TCGA and GTEx data were analyzed using the GEPIA2 platform. Cell viability under drug treatment was assessed using Alamar Blue reagent; the interaction between G9a and niclosamide was assessed using molecular docking analysis; mRNA and protein expression were quantified in DLBCL cell lines. Finally, G9a expression was quantified in 39 DLBCL patient samples. Results: The TCGA database analysis revealed higher G9a mRNA expression in DLBCL compared to normal tissues. Niclosamide inhibited DLBCL cell line proliferation in a time- and dose-dependent manner, reducing G9a expression and increasing p62, BECN1, and LC3 gene expression by autophagy pathway regulation. There was a correlation between G9a expression in DLBCL samples and clinical data, showing that advanced cancer stages exhibited a higher proportion of G9a-expressing cells. Conclusion: G9a overexpression is associated with tumor progression in DLBCL. Niclosamide effectively inhibits DLBCL growth by reducing G9a expression via the cellular autophagy pathway; therefore, G9a is a potential molecular target for the development of therapeutic strategies for DLBCL.

出版狀態Published - 2023 8月

All Science Journal Classification (ASJC) codes

  • 腫瘤科
  • 癌症研究


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