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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/14130
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| Title: | Inhibition of KDM4C/c-Myc/LDHA signalling axis suppresses prostate cancer metastasis via interference of glycolytic metabolism |
| Authors: | Lin, CY;Wang, BJ;Fu, YK;Huo, C;Wang, YP;Chen, BC;Liu, WY;Tseng, JC;Jiang, SS;Sie, ZL;Tsai, KK;Yuh, CH;Wang, WC;Kung, HJ;Chuu, CP |
| Contributors: | Institute of Cellular and Systems Medicine;National Institute of Cancer Research;Immunology Research Center |
| Abstract: | Dear Editor, we discovered that knockout of KDM4C can effectively suppress prostate cancer (PCa) cellsâ migration and invasion. We identified that targeting KDM4C/c-Myc/LDHA signalling can be an effective prevention for metastatic PCa. Epigenetics change is an important feature in cancer metabolism reprograming and metabolism rewiring can enhance cancer progression. Histone lysine demethylase 4C (KDM4C), which can remove the dimethyl/trimethyl group from H3K9 or H3K36, is an androgen receptor (AR) co-regulator. KDM4C is elevated in castration-resistant prostate cancer (CRPC)1 and elevation of KDM4C stimulates the proliferation of PCa cells.2 However, how KDM4C regulates PCa metastasis or cancer metabolism is unclear. We examined the KDM4C gene level in online gene datasets Gene Expression Omnibus (GEO) profile GDS 2547 (HG-U95C) (Figure 1A), The Cancer Genome Atlas (TCGA) Prostate Adenocarcinoma (PRAD) (Supplemental Figure S1), Chandran PCa dataset (Figure 1B), Grasso PCa dataset (Figure 1C) and LaTulippe PCa dataset (Figure 1D). Expression level of KDM4C gene was increased in metastatic prostate cancer (PCa). To study how KDM4C promotes PCa metastasis, CRISPR/Cas9 single-guide RNA (sgRNA) was constructed in C4-2B PCa cells (Supplemental Figure S2), which impaired KDM4C's demethylation ability (Supplemental Figure S3). Knockout of KDM4C suppressed C4-2B cellsâ ability to migrate and to invade (Figure 1E). Knockdown of KDM4C with siRNA also repressed the migration and invasion of LNCaP cells (Figure 1F). Treatment with SD70, a potent and selective inhibitor for KDM4C, repressed the migration and invasion of both C4-2B and LNCaP (Figure 1GâJ) cells. KDM4C knockout decreased metastatic distance of C4-2B PCa tumours in zebrafish xenotransplantation model (Figure 1KâM). Oppositely, overexpression of KDM4C promoted the migration of DU-145 cells (Supplemental Figure S4). |
| Date: | 2022-03 |
| Relation: | Clinical and Translational Medicine. 2022 Mar;12(3):Article number e764. |
| Link to: | http://dx.doi.org/10.1002/ctm2.764 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2001-1326&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000773465300001 |
| Appears in Collections: | [褚志斌] 期刊論文
[喻秋華] 期刊論文
[江士昇] 期刊論文
[其他] 期刊論文
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