COL10A1,也称为Collagen type X alpha 1 chain,是编码X型胶原蛋白α1链的基因。X型胶原蛋白是一种非纤维胶原蛋白,主要存在于长骨的软骨组织中,是软骨细胞肥大分化的标志性基因,与骨骼生长密切相关。COL10A1的表达受多种转录因子的调控,包括Stat5a、Mef2a等,这些转录因子通过与其启动子或增强子区域的结合,影响COL10A1的表达和软骨细胞的肥大分化[1,3]。
研究发现,Stat5a是COL10A1的一个重要正调控因子。Stat5a与COL10A1顺式增强子的相互作用,可以增强COL10A1的转录活性,促进软骨细胞的肥大分化[1]。此外,Mef2a也被证实可以与COL10A1的顺式增强子结合,并增强COL10A1的表达[3]。这些研究结果提示,Stat5a和Mef2a可能通过相互作用,共同调控COL10A1的表达和软骨细胞的肥大分化。
除了在骨骼生长中的作用,COL10A1在肿瘤发生发展中也发挥着重要作用。研究发现,COL10A1在多种肿瘤中表达上调,包括乳腺癌、胰腺癌、膀胱癌和前列腺癌等,且其表达水平与患者的预后不良相关[2,4,5,6]。例如,在乳腺癌中,COL10A1的表达水平与患者的总体生存率、无复发生存率、无远处转移生存率和无病生存率均呈负相关[2]。在胰腺癌中,COL10A1通过调节CD276的表达,促进肿瘤的发生发展[4]。在膀胱癌中,COL10A1的表达水平与患者的总体生存率相关,且其可能通过影响肿瘤浸润免疫细胞和调节免疫,影响患者的预后[6]。在前列腺癌中,COL10A1的表达水平与肿瘤的增殖、迁移和侵袭能力相关,提示其可能作为前列腺癌的预后标志物和治疗靶点[7]。
综上所述,COL10A1是一个在骨骼生长和肿瘤发生发展中发挥重要作用的基因。Stat5a和Mef2a等转录因子通过与其启动子或增强子区域的结合,调控COL10A1的表达和软骨细胞的肥大分化。在肿瘤中,COL10A1的表达上调与患者的预后不良相关,且其可能通过调节CD276、影响肿瘤浸润免疫细胞和调节免疫等机制,促进肿瘤的发生发展。因此,COL10A1的研究对于深入理解骨骼生长和肿瘤发生发展的机制,以及寻找新的治疗靶点具有重要意义。
参考文献:
1. Wu, Xuan, Chen, Chen, Han, Tiaotiao, Qiao, Longwei, Zheng, Qiping. 2023. Stat5a promotes Col10a1 gene expression during chondrocyte hypertrophic differentiation. In American journal of translational research, 15, 4006-4019. doi:. https://pubmed.ncbi.nlm.nih.gov/37434818/
2. Zhang, Mingdi, Chen, Hongliang, Wang, Maoli, Bai, Fang, Wu, Kejin. . Bioinformatics analysis of prognostic significance of COL10A1 in breast cancer. In Bioscience reports, 40, . doi:10.1042/BSR20193286. https://pubmed.ncbi.nlm.nih.gov/32043519/
3. Chen, Chen, Wu, Xuan, Han, Tiaotiao, Qiao, Longwei, Zheng, Qiping. 2023. Mef2a is a positive regulator of Col10a1 gene expression during chondrocyte maturation. In American journal of translational research, 15, 4020-4032. doi:. https://pubmed.ncbi.nlm.nih.gov/37434855/
4. Xu, Qiaodong, Zheng, Jieting, Su, Zegeng, Chen, Binlie, Gu, Songgang. 2023. COL10A1 promotes tumorigenesis by modulating CD276 in pancreatic adenocarcinoma. In BMC gastroenterology, 23, 397. doi:10.1186/s12876-023-03045-2. https://pubmed.ncbi.nlm.nih.gov/37974070/
5. Yi, Qiang, Zhu, Gangfeng, Zhu, Weijian, Yang, Kuan, Zhong, Jinghua. 2024. Oncogenic mechanisms of COL10A1 in cancer and clinical challenges (Review). In Oncology reports, 52, . doi:10.3892/or.2024.8821. https://pubmed.ncbi.nlm.nih.gov/39392043/
6. Wang, Xiaoming, Bai, Yunjin, Zhang, Facai, Wei, Xin, Han, Ping. 2023. Prognostic value of COL10A1 and its correlation with tumor-infiltrating immune cells in urothelial bladder cancer: A comprehensive study based on bioinformatics and clinical analysis validation. In Frontiers in immunology, 14, 955949. doi:10.3389/fimmu.2023.955949. https://pubmed.ncbi.nlm.nih.gov/37006317/
7. Xu, Shengxian, Liu, Dongze, Qin, Zheng, Xu, Yong, Zhang, Hongtuan. 2023. Experimental validation and pan-cancer analysis identified COL10A1 as a novel oncogene and potential therapeutic target in prostate cancer. In Aging, 15, 15134-15160. doi:10.18632/aging.205337. https://pubmed.ncbi.nlm.nih.gov/38147021/