Golgi integral membrane protein 4 (GOLIM4), also known as Golgi apparatus transporter complex member, is a key protein associated with the Golgi apparatus. It plays essential roles in coordinating Ca2+-dependent cargo loading, Golgi membrane bending, and vesicle scission, thus being involved in the secretory pathway [2]. It also helps maintain intracellular manganese (Mn) homeostasis [2].

In nasopharyngeal carcinoma (NPC), the long isoform of GOLIM4 (-L) with exon-7 is highly expressed and linked to poor prognosis. RBFOX2, a splicing regulator, binds to exon-7 of GOLIM4 and promotes the formation of GOLIM4-L. Knocking down either RBFOX2 or GOLIM4-L suppresses NPC cell tumorigenesis, and GOLIM4-L overexpression can rescue this effect. RBFOX2 and GOLIM4 can influence vesicle-mediated transport through maintaining Golgi apparatus organization, and RAB26 interacts with GOLIM4 to mediate its tumorigenic potentials in NPC cells [1]. In breast cancer, circ_RNF10 can inhibit tumorigenicity by targeting the miR-942-5p/GOLIM4 axis, and miR-105-3p acts as an oncogene to promote breast cancer cell proliferation and metastasis by targeting GOLIM4 [3,4]. In head and neck cancer, knockdown of GOLIM4 inhibits cell proliferation, promotes apoptosis, and regulates cell cycle progression [5].

In summary, GOLIM4 is crucial for the secretory pathway and maintaining Mn homeostasis. Studies, including those in cancer models, have revealed its significant role in tumorigenesis of multiple cancers, such as NPC, breast cancer, and head and neck cancer. These findings highlight its potential as a therapeutic target in related diseases.

References:

1. Luo, Chun-Ling, Xu, Xiao-Chen, Liu, Chu-Jun, Xia, Xiao-Jun, Bei, Jin-Xin. 2021. RBFOX2/GOLIM4 Splicing Axis Activates Vesicular Transport Pathway to Promote Nasopharyngeal Carcinogenesis. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 8, e2004852. doi:10.1002/advs.202004852. https://pubmed.ncbi.nlm.nih.gov/34180133/

2. Tan, Xiaochao, Wang, Shike, Xiao, Guan-Yu, Russell, William K, Kurie, Jonathan M. 2024. Chromosomal 3q amplicon encodes essential regulators of secretory vesicles that drive secretory addiction in cancer. In The Journal of clinical investigation, 134, . doi:10.1172/JCI176355. https://pubmed.ncbi.nlm.nih.gov/38662435/

3. Kan, Binghua, Yan, Guiru, Shao, Yuan, Zhang, Ziliang, Xue, Hui. 2022. CircRNA RNF10 inhibits tumorigenicity by targeting miR-942-5p/GOLIM4 axis in breast cancer. In Environmental and molecular mutagenesis, 63, 362-372. doi:10.1002/em.22506. https://pubmed.ncbi.nlm.nih.gov/36054164/

4. Lin, Bo, Liu, Chunhua, Shi, Enyi, Wang, Juan, Ji, Runyuan. 2021. MiR-105-3p acts as an oncogene to promote the proliferation and metastasis of breast cancer cells by targeting GOLIM4. In BMC cancer, 21, 275. doi:10.1186/s12885-021-07909-2. https://pubmed.ncbi.nlm.nih.gov/33722196/

5. Bai, Yunfei, Cui, Xiaobo, Gao, Dongxue, Wang, Boqian, Wang, Wei. 2018. Golgi integral membrane protein 4 manipulates cellular proliferation, apoptosis, and cell cycle in human head and neck cancer. In Bioscience reports, 38, . doi:10.1042/BSR20180454. https://pubmed.ncbi.nlm.nih.gov/30068697/