Apolipoprotein C1 (APOC1) is a member of the apolipoprotein family and is critical in the metabolism of very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) cholesterols [6]. It has been associated with multiple biological processes and diseases, making it an important gene for functional studies.

In various cancers, APOC1 has shown significant impacts. In hepatocellular carcinoma, inhibition of APOC1 in APOC1-/-C57BL/6 mice promoted the transformation of M2 macrophages into M1 macrophages via the ferroptosis pathway, reshaping the tumor immune microenvironment and enhancing anti-PD1 immunotherapy [1]. In renal cell cancer, co-culture with RCC cells induced the generation of M2-phenotype TAMs, which was blocked by silencing APOC1, and APOC1 promoted M2 polarization of macrophages [3]. In nonsmall cell lung cancer, APOC1 reduced anti-PD-1 immunotherapy via the transformation of M2 into M1 macrophages by ferroptosis through the NRF2/HO-1 pathway [7]. In osteosarcoma, APOC1 promoted progression by binding to MTCH2, and M2 macrophage exosome-derived Apoc1 promoted ferroptosis resistance in osteosarcoma [5,10]. In addition, APOC1 was identified as a core secretory gene in IgA nephropathy, exacerbating renal fibrosis possibly by activating the NF-κB pathway, and might be a novel diagnostic biomarker for diabetic nephropathy [4,8]. In esophageal cancer, overexpression of APOC1 was associated with poor prognosis, and inhibition of its expression reduced cell proliferation, migration, and invasion [9]. In ovarian cancer, APOC1 was upregulated, and patients with high APOC1 levels had a poorer prognosis, and it was associated with M2 TAMs [2]. In glioma, silencing APOC1 in glioma cell lines decreased cell proliferation, migration, and invasion, and APOC1 promoted metastasis through the epithelial-mesenchymal transition and activation of the STAT3 pathway [6].

In conclusion, APOC1 is not only crucial in lipoprotein metabolism but also plays significant roles in multiple diseases, especially in cancer progression and immune microenvironment regulation. Gene knockout (KO) mouse models, such as the APOC1-/-C57BL/6 mice, have been instrumental in revealing its functions in these disease conditions, providing potential therapeutic targets and diagnostic biomarkers for various diseases.

References:

1. Hao, Xiaopei, Zheng, Zhiying, Liu, Hanyuan, Tang, Weiwei, Wang, Xuehao. 2022. Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing. In Redox biology, 56, 102463. doi:10.1016/j.redox.2022.102463. https://pubmed.ncbi.nlm.nih.gov/36108528/

2. Yang, Shimin, Du, Jingxiao, Wang, Wei, Zhou, Dongmei, Xi, Xiaowei. 2024. APOC1 is a prognostic biomarker associated with M2 macrophages in ovarian cancer. In BMC cancer, 24, 364. doi:10.1186/s12885-024-12105-z. https://pubmed.ncbi.nlm.nih.gov/38515073/

3. Ren, Liwen, Yi, Jie, Yang, Yihui, Wang, Xifu, Wang, Jinhua. 2022. Systematic pan-cancer analysis identifies APOC1 as an immunological biomarker which regulates macrophage polarization and promotes tumor metastasis. In Pharmacological research, 183, 106376. doi:10.1016/j.phrs.2022.106376. https://pubmed.ncbi.nlm.nih.gov/35914680/

4. Yu, Kuipeng, Ding, Lin, An, Xin, Bai, Fang, Yang, Xiangdong. 2023. APOC1 exacerbates renal fibrosis through the activation of the NF-κB signaling pathway in IgAN. In Frontiers in pharmacology, 14, 1181435. doi:10.3389/fphar.2023.1181435. https://pubmed.ncbi.nlm.nih.gov/37305534/

5. Li, Renjie, He, Huixian, He, Xinxin. 2023. APOC1 promotes the progression of osteosarcoma by binding to MTCH2. In Experimental and therapeutic medicine, 25, 163. doi:10.3892/etm.2023.11862. https://pubmed.ncbi.nlm.nih.gov/36911382/

6. Liang, Rui, Zhang, Guofeng, Xu, Wenhua, Liu, Weibing, Tang, Youjia. 2022. ApoC1 promotes glioma metastasis by enhancing epithelial-mesenchymal transition and activating the STAT3 pathway. In Neurological research, 45, 268-275. doi:10.1080/01616412.2022.2132458. https://pubmed.ncbi.nlm.nih.gov/36302088/

7. Mei, Langhua, Long, Jian, Wu, Shue, Mei, Di, Qiu, Huaping. 2024. APOC1 reduced anti-PD-1 immunotherapy of nonsmall cell lung cancer via the transformation of M2 into M1 macrophages by ferroptosis by NRF2/HO-1. In Anti-cancer drugs, 35, 333-343. doi:10.1097/CAD.0000000000001573. https://pubmed.ncbi.nlm.nih.gov/38241194/

8. Yu, Kuipeng, Li, Shan, Wang, Chunjie, Sun, Jintang, Yang, Xiangdong. 2023. APOC1 as a novel diagnostic biomarker for DN based on machine learning algorithms and experiment. In Frontiers in endocrinology, 14, 1102634. doi:10.3389/fendo.2023.1102634. https://pubmed.ncbi.nlm.nih.gov/36891052/

9. Guo, Qiang, Liu, Xiao-Li, Jiang, Ni, Zhang, Jun, Liu, Hua-Song. 2022. Decreased APOC1 expression inhibited cancer progression and was associated with better prognosis and immune microenvironment in esophageal cancer. In American journal of cancer research, 12, 4904-4929. doi:. https://pubmed.ncbi.nlm.nih.gov/36504892/

10. Yin, Ping, Tang, Min, Zhao, Guosheng. 2024. M2 macrophage exosome-derived Apoc1 promotes ferroptosis resistance in osteosarcoma by inhibiting ACSF2 deubiquitination. In Molecular carcinogenesis, 63, 2103-2118. doi:10.1002/mc.23796. https://pubmed.ncbi.nlm.nih.gov/39041949/