RASEF, also known as Rab45, is an atypical Rab GTPase. It contains N-terminal EF-hand and coiled-coil domains, as well as a C-terminal Rab-GTPase domain. It is involved in membrane trafficking and may play important roles in various biological processes [2,7].

In pancreatic acinar cells, RASEF-knockout (KO) mice studies revealed that RASEF regulates the formation and sorting of zymogen granules and secretion of digestive enzymes. Pancreatic acinar cells in RASEF-KO mice had an increased number of zymogen granules, abnormal organelle formations, and impaired enzyme release upon cerulein administration [2].

In the context of diseases, in colorectal cancer, high RASEF expression was associated with a better prognosis, and it may be a suppressor gene inhibiting cancer development through DNA repair processes [1]. In breast cancer, RASEF mRNA expression levels were associated with hormone receptor status, with lower levels in negative hormone receptor status patients [3]. In lung cancer, elevated RASEF promoted cell growth via enhanced ERK signaling and was associated with poor prognosis [5]. In uveal melanoma, low RASEF expression correlated with promoter methylation and was associated with decreased survival, suggesting a tumor-suppressor role [6]. In cigarette smoke-induced pulmonary arterial smooth muscle remodeling, RASEF hypermethylation was related to PA remodeling, and its overexpression inhibited PH and HPASMCs remodeling [4].

In conclusion, RASEF is a crucial gene involved in membrane-related functions and has significant implications in multiple disease areas. Studies using RASEF-KO mouse models have provided valuable insights into its role in pancreatic function and shed light on its potential as a therapeutic target or prognostic biomarker in various cancers and pulmonary hypertension [1-7].

References:

1. Yu, Xin, Fang, Zhenhuan, Li, Guodong, Liu, Ming, Wang, Ying. 2018. High RASEF expression is associated with a significantly better prognosis in colorectal cancer. In International journal of clinical and experimental pathology, 11, 4276-4282. doi:. https://pubmed.ncbi.nlm.nih.gov/31949824/

2. Sato, Keiko, Kadowaki, Tomoko, Takenaka, Mamoru, Onodera, Takae, Tsukuba, Takayuki. 2024. RASEF/Rab45 regulates the formation and sorting of zymogen granules and secretion of digestive enzymes by pancreatic acinar cells. In Biochimica et biophysica acta. Molecular basis of disease, 1870, 167310. doi:10.1016/j.bbadis.2024.167310. https://pubmed.ncbi.nlm.nih.gov/38901651/

3. Shibata, Masahiro, Kanda, Mitsuro, Shimizu, Dai, Kodera, Yasuhiro, Kikumori, Toyone. 2018. RASEF expression correlates with hormone receptor status in breast cancer. In Oncology letters, 16, 7223-7230. doi:10.3892/ol.2018.9542. https://pubmed.ncbi.nlm.nih.gov/30546460/

4. Li, Qinghai, Wu, Jixing, Xu, Yongjian, Liu, Lu, Xie, Jungang. 2019. Role of RASEF hypermethylation in cigarette smoke-induced pulmonary arterial smooth muscle remodeling. In Respiratory research, 20, 52. doi:10.1186/s12931-019-1014-1. https://pubmed.ncbi.nlm.nih.gov/30845941/

5. Oshita, Hideto, Nishino, Ryohei, Takano, Atsushi, Nakamura, Yusuke, Daigo, Yataro. 2013. RASEF is a novel diagnostic biomarker and a therapeutic target for lung cancer. In Molecular cancer research : MCR, 11, 937-51. doi:10.1158/1541-7786.MCR-12-0685-T. https://pubmed.ncbi.nlm.nih.gov/23686708/

6. Maat, Willem, Beiboer, Sigrid H W, Jager, Martine J, Gruis, Nelleke A, van der Velden, Pieter A. . Epigenetic regulation identifies RASEF as a tumor-suppressor gene in uveal melanoma. In Investigative ophthalmology & visual science, 49, 1291-8. doi:10.1167/iovs.07-1135. https://pubmed.ncbi.nlm.nih.gov/18385040/

7. Shintani, Mami, Tada, Minoru, Kobayashi, Tetsuo, Kontani, Kenji, Katada, Toshiaki. 2007. Characterization of Rab45/RASEF containing EF-hand domain and a coiled-coil motif as a self-associating GTPase. In Biochemical and biophysical research communications, 357, 661-7. doi:. https://pubmed.ncbi.nlm.nih.gov/17448446/