Nrg2, a member of the neuregulin family, belongs to the EGF family of growth factors. It contains a receptor-binding EGF-like domain and mediates binding to cellular receptors, with its functions potentially related to multiple cellular processes [1,7].

In cancer, NRG2 fusions have been identified in solid tumors and may contribute to oncogenesis through ligand-fusion mechanisms, potentially enhancing ectopic expression of the NRG/ErbB receptor-ligand and triggering downstream pathways [1,4,6].

In prostate regeneration, mesenchymal cells can express Nrg2 in an androgen-driven manner, acting in a paracrine fashion on luminal cells to contribute to prostate regeneration [2].

In gliomas, NRG2 is expressed to varying extents and can promote the migration of glioma cells in vitro, suggesting that targeting NRG2 signaling may reverse glioma cell metastasis [3].

In breast cancer, NRG2 acts as a tumor suppressor, and its low expression is related to poor survival rate, with its depletion promoting cancer cell proliferation, invasion, and migration [5].

No KO/CKO mouse models were directly mentioned in the provided references. However, from the studies on different diseases, we can infer that Nrg2 has diverse functions. In solid tumors, its fusion may drive oncogenesis; in prostate, it is involved in regeneration; in gliomas, it affects cell migration; and in breast cancer, it acts as a tumor suppressor. Although not demonstrated through KO/CKO mouse models in these references, these findings suggest the importance of further in-vivo studies, potentially using gene knockout models, to fully understand the role of Nrg2 in these biological processes and disease conditions.

In conclusion, Nrg2 is involved in multiple biological processes and disease conditions. Its functions range from promoting prostate regeneration to playing a role in the development and progression of various cancers, such as solid tumors, gliomas, and breast cancer. While the exact mechanisms are yet to be fully elucidated, especially through gene-knockout-based in-vivo studies, the current findings highlight its significance in understanding disease mechanisms and potentially developing targeted therapies.

References:

1. Nagasaka, Misako, Ou, Sai-Hong Ignatius. 2022. NRG1 and NRG2 fusion positive solid tumor malignancies: a paradigm of ligand-fusion oncogenesis. In Trends in cancer, 8, 242-258. doi:10.1016/j.trecan.2021.11.003. https://pubmed.ncbi.nlm.nih.gov/34996744/

2. Karthaus, Wouter R, Hofree, Matan, Choi, Danielle, Regev, Aviv, Sawyers, Charles L. . Regenerative potential of prostate luminal cells revealed by single-cell analysis. In Science (New York, N.Y.), 368, 497-505. doi:10.1126/science.aay0267. https://pubmed.ncbi.nlm.nih.gov/32355025/

3. Zhao, Wei-Jiang, Yi, San-Jun, Ou, Guan-Yong, Qiao, Xin-Yu. . Neuregulin 2 (NRG2) is expressed in gliomas and promotes migration of human glioma cells. In Folia neuropathologica, 59, 189-197. doi:10.5114/fn.2021.106460. https://pubmed.ncbi.nlm.nih.gov/34284546/

4. Trombetta, Domenico, Sparaneo, Angelo, Fabrizio, Federico Pio, Rossi, Antonio, Muscarella, Lucia Anna. 2021. NRG1 and NRG2 fusions in non-small cell lung cancer (NSCLC): seven years between lights and shadows. In Expert opinion on therapeutic targets, 25, 865-875. doi:10.1080/14728222.2021.1999927. https://pubmed.ncbi.nlm.nih.gov/34706602/

5. Zhou, Ruijie, Dai, Jinjin, Zhou, Runlong, Yao, Di, Xu, Yao. 2024. Prognostic biomarker NRG2 correlates with autophagy and epithelial‑mesenchymal transition in breast cancer. In Oncology letters, 27, 277. doi:10.3892/ol.2024.14410. https://pubmed.ncbi.nlm.nih.gov/38699660/

6. Xu, Chunwei, Wang, Qian, Wang, Dong, Chen, Jing, Song, Zhengbo. 2024. Expert Consensus on the Diagnosis and Treatment of NRG1/2 Gene Fusion Solid Tumors. In Global medical genetics, 11, 86-99. doi:10.1055/s-0044-1781457. https://pubmed.ncbi.nlm.nih.gov/38414979/

7. Czarnek, Maria, Bereta, Joanna. 2019. Proteolytic Processing of Neuregulin 2. In Molecular neurobiology, 57, 1799-1813. doi:10.1007/s12035-019-01846-9. https://pubmed.ncbi.nlm.nih.gov/31838721/