Chsy1, or chondroitin sulfate synthase 1, is a glycosyltransferase involved in the synthesis of chondroitin sulfate. It participates in multiple biological processes and is associated with pathways like BMP signaling, succinate metabolism, and PI3K/AKT/HIF1A [1,2]. It holds significance in maintaining extracellular matrix (ECM) homeostasis and is linked to various diseases, making genetic models crucial for its study.

In cancer research, Chsy1 deficiency has been studied. In CRC, CHSY1 promotes liver metastasis by activating the succinate metabolism pathway, inducing CD8+ T cell exhaustion and upregulating PD-L1 expression [1]. In gastric cancer, CHSY1 knockdown inhibits cell proliferation, colony formation, and migration while promoting apoptosis [3]. In glioma, depletion of lncRNA LINC01094, which up-regulates CHSY1 by sponging miR-224-5p, impairs cell viability, colony formation, migration, and invasion [5]. In HCC, silencing CHSY1 suppresses cell growth, migration, invasion, and epithelial-mesenchymal transition [7]. In colorectal cancer, CHSY1 knockdown decreases cell proliferation, increases apoptosis, and affects related signaling pathways like NFκB and caspase-3/7 [8]. In oral squamous cell carcinoma, knockdown of circ_0005050, which acts through the miR-487a-3p/CHSY1 axis, retards cell growth [9].

In OA research, Chsy1 deficiency in mouse ATDC5 chondrocytes reduces ECM production, promotes endochondral osteogenesis, and aggravates cartilage injury [2]. In intervertebral disc (IVD) research, genetic sensory denervation of IVD leads to reduced Chsy1 expression and dysregulated ECM homeostasis, and knockdown of CGRP in sensory nerves has a similar effect which is abolished in CHSY1 knockout mice [4]. In peripheral nerve injury research, in vivo siRNA transfection to silence Chsy1 at the nerve lesion site in rats is associated with functional recovery and decreased versican accumulation [6].

In conclusion, Chsy1 plays essential roles in maintaining ECM homeostasis and is involved in various disease conditions such as cancer, osteoarthritis, and IVD degeneration. Studies using gene knockout models in mice have revealed its role in promoting cancer metastasis, regulating cell proliferation and apoptosis in cancer, and affecting ECM-related processes in OA and IVD. These findings provide potential therapeutic targets for these diseases [1-9].

References:

1. Sun, Guangshun, Zhao, Siqi, Fan, Zhongguo, Gao, Yun, Tang, Weiwei. 2023. CHSY1 promotes CD8+ T cell exhaustion through activation of succinate metabolism pathway leading to colorectal cancer liver metastasis based on Nuclease technology screening. In Journal of experimental & clinical cancer research : CR, 42, 248. doi:10.1186/s13046-023-02803-0. https://pubmed.ncbi.nlm.nih.gov/37749638/

2. Lyu, Zhaojie, Da, Yifeng, Liu, Hongkai, Zhu, Yong, Tian, Jing. 2022. Chsy1 deficiency reduces extracellular matrix productions and aggravates cartilage injury in osteoarthritis. In Gene, 827, 146466. doi:10.1016/j.gene.2022.146466. https://pubmed.ncbi.nlm.nih.gov/35390446/

3. Liu, Jingjing, Tian, Zhenwei, Liu, Tianzhou, Liu, Yuanda, Zhu, Jiaming. 2021. CHSY1 is upregulated and acts as tumor promotor in gastric cancer through regulating cell proliferation, apoptosis, and migration. In Cell cycle (Georgetown, Tex.), 20, 1861-1874. doi:10.1080/15384101.2021.1963553. https://pubmed.ncbi.nlm.nih.gov/34412565/

4. Hu, Bo, Lv, Xiao, Wei, Leixin, Xu, Chen, Chen, Huajiang. 2022. Sensory Nerve Maintains Intervertebral Disc Extracellular Matrix Homeostasis Via CGRP/CHSY1 Axis. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 9, e2202620. doi:10.1002/advs.202202620. https://pubmed.ncbi.nlm.nih.gov/36047655/

5. Liu, Luotong, Xu, Qian, Xiong, Yu, Deng, Huajiang, Zhou, Jie. 2021. LncRNA LINC01094 contributes to glioma progression by modulating miR-224-5p/CHSY1 axis. In Human cell, 35, 214-225. doi:10.1007/s13577-021-00637-6. https://pubmed.ncbi.nlm.nih.gov/34716872/

6. Liu, Chiung-Hui, Ho, Ying-Jui, Wang, Che-Yu, Hsiao, Wen-Chuan, Liao, Wen-Chieh. 2023. Targeting Chondroitin Sulphate Synthase 1 (Chsy1) Promotes Axon Growth Following Neurorrhaphy by Suppressing Versican Accumulation. In Molecules (Basel, Switzerland), 28, . doi:10.3390/molecules28093742. https://pubmed.ncbi.nlm.nih.gov/37175152/

7. Liu, Chiung-Hui, Lan, Chyn-Tair, Chou, Jui-Feng, Tseng, To-Jung, Liao, Wen-Chieh. 2017. CHSY1 promotes aggressive phenotypes of hepatocellular carcinoma cells via activation of the hedgehog signaling pathway. In Cancer letters, 403, 280-288. doi:10.1016/j.canlet.2017.06.023. https://pubmed.ncbi.nlm.nih.gov/28652022/

8. Zeng, Lifeng, Qian, Jinrong, Luo, Xiaojiang, Zhang, Zhiyong, Fang, Quangang. 2018. CHSY1 promoted proliferation and suppressed apoptosis in colorectal cancer through regulation of the NFκB and/or caspase-3/7 signaling pathway. In Oncology letters, 16, 6140-6146. doi:10.3892/ol.2018.9385. https://pubmed.ncbi.nlm.nih.gov/30344756/

9. Chen, Xubin, Chen, Qiaojiang, Zhao, Chen, Lu, Zhiqi. 2022. Hsa_circ_0005050 regulated the progression of oral squamous cell carcinoma via miR-487a-3p/CHSY1 axis. In Journal of dental sciences, 18, 282-294. doi:10.1016/j.jds.2022.05.012. https://pubmed.ncbi.nlm.nih.gov/36643258/