Asap2-KO Mouse

ASAP2, or ArfGAP With SH3 Domain, Ankyrin Repeat And PH Domain 2, is a gene encoding a GTPase-activating protein. It is involved in regulating vesicular transport, cellular migration, and autophagy, and is a primary target of 1,25-dihydroxyvitamin D3 in human monocytes and macrophages [5,6]. It also participates in receptor tyrosine kinase signaling pathways [1].

In hepatocellular carcinoma (HCC), ASAP2 is highly expressed and predicts poor prognosis. Knockdown of ASAP2 in HCC cells impairs cell proliferation, migration, and invasion, and promotes apoptosis both in vitro and in vivo. Mechanistically, ASAP2 binds to CIN85, disrupting its interaction with c-MET, thus sustaining HGF/c-MET-induced malignant potentials [1]. In pancreatic cancer, ASAP2 is overexpressed based on increased DNA copy numbers, and high expression contributes to a poor prognosis. ASAP2-knockout pancreatic ductal adenocarcinoma (PDAC) cells show that ASAP2 promotes tumor growth by facilitating cell cycle progression through phosphorylation of epidermal growth factor receptor (EGFR) [3]. In gastric cancer, circ_ASAP2 promotes cell viability, migration, and invasion. Knockdown of circ_ASAP2 inhibits these processes, suggesting its potential as a therapeutic target [4]. In diabetic nephropathy, inhibition of circ_ASAP2 aggravates the disease, promoting inflammation, oxidative stress, and ferroptosis [2].

In conclusion, ASAP2 plays crucial roles in multiple biological processes and disease conditions. Gene-knockout models, such as in HCC and PDAC, have revealed its functions in promoting cancer cell growth, migration, and invasion. In diabetic nephropathy, studies on circ_ASAP2 also highlight its importance in regulating disease-related processes. Understanding ASAP2 functions can potentially lead to new therapeutic strategies for these diseases.

References:

1. Ma, Xiao-Lu, Nie, Yan-Yan, Xie, Su-Hong, Guo, Lin, Lu, Ren-Quan. 2023. ASAP2 interrupts c-MET-CIN85 interaction to sustain HGF/c-MET-induced malignant potentials in hepatocellular carcinoma. In Experimental hematology & oncology, 12, 38. doi:10.1186/s40164-023-00393-3. https://pubmed.ncbi.nlm.nih.gov/37061723/

2. Li, Qin, Meng, Xiangjian, Hua, Qiang. 2022. Circ ASAP2 decreased inflammation and ferroptosis in diabetic nephropathy through SOX2/SLC7A11 by miR-770-5p. In Acta diabetologica, 60, 29-42. doi:10.1007/s00592-022-01961-5. https://pubmed.ncbi.nlm.nih.gov/36153434/

3. Fujii, Atsushi, Masuda, Takaaki, Iwata, Michio, Nakamura, Masafumi, Mimori, Koshi. 2021. The novel driver gene ASAP2 is a potential druggable target in pancreatic cancer. In Cancer science, 112, 1655-1668. doi:10.1111/cas.14858. https://pubmed.ncbi.nlm.nih.gov/33605496/

4. Chen, Bing, Ji, Fei, Wen, Xinian, Jin, Zhong. 2020. Circular RNA circ_ASAP2 promotes cell viability, migration, and invasion of gastric cancer cells by regulating the miR-770-5p/CDK6 axis. In International journal of clinical and experimental pathology, 13, 2806-2819. doi:. https://pubmed.ncbi.nlm.nih.gov/33284890/

5. Shi, Hui, Duan, Jiangling, Wang, Jiayu, Wu, Xueyan, Lu, Ming. 2022. 1,25(OH)2D3 Promotes Macrophage Efferocytosis Partly by Upregulating ASAP2 Transcription via the VDR-Bound Enhancer Region and ASAP2 May Affect Antiviral Immunity. In Nutrients, 14, . doi:10.3390/nu14224935. https://pubmed.ncbi.nlm.nih.gov/36432619/

6. Seuter, Sabine, Ryynänen, Jussi, Carlberg, Carsten. 2013. The ASAP2 gene is a primary target of 1,25-dihydroxyvitamin D3 in human monocytes and macrophages. In The Journal of steroid biochemistry and molecular biology, 144 Pt A, 12-8. doi:10.1016/j.jsbmb.2013.08.014. https://pubmed.ncbi.nlm.nih.gov/23999061/