TRIM36, also known as Haprin, is a member of the tripartite motif (TRIM) family of RING-containing proteins. It is a microtubule-associated E3 ubiquitin ligase, playing a role in cytoskeletal organization by coordinating microtubule growth speed and stability at the plus end, thus impacting cell cycle progression. It is crucial for early developmental processes, like dorso-ventral axis formation in Xenopus, and its bi-allelic mutations in humans cause anencephaly, a severe neural tube closure defect [1].

In cancer research, TRIM36 has been shown to have anti-tumor effects in many cancers. In hepatocellular carcinoma (HCC), its down-regulation in cancer tissues was observed, and it was found to inhibit proliferation, migration, and invasion while promoting apoptosis via the Wnt/β-catenin pathway [2]. Similar anti-tumor functions were seen in lung adenocarcinoma, where it enhanced radiosensitivity, and in esophageal squamous cell carcinoma, where it suppressed cell growth by inhibiting the Wnt/β-catenin signaling pathway [3,4]. In prostate cancer, TRIM36 inhibited the neuroendocrine differentiation of prostate cancer cells by regulating HK2 ubiquitination and GPx4 deficiency [5]. However, in kidney renal clear cell carcinoma (KIRC), increased TRIM36 expression was associated with a poorer prognosis, and it promoted cell proliferation and migration [6].

In conclusion, TRIM36 is essential for embryonic development and spermatogenesis. Its role in the cytoskeleton and cell cycle regulation has significant implications. In cancer, depending on the type of cancer, TRIM36 can either act as a tumor suppressor or be associated with poor prognosis. Studies on TRIM36 using gene knockout or conditional knockout mouse models could potentially further clarify its functions in these biological processes and diseases.

References:

1. Mascaro, Martina, Lages, Inês, Meroni, Germana. 2022. Microtubular TRIM36 E3 Ubiquitin Ligase in Embryonic Development and Spermatogenesis. In Cells, 11, . doi:10.3390/cells11020246. https://pubmed.ncbi.nlm.nih.gov/35053362/

2. Tong, Qing, Yi, Mingyu, Kong, Panpan, Tian, Rui, Yan, Dong. 2022. TRIM36 inhibits tumorigenesis through the Wnt/β-catenin pathway and promotes caspase-dependent apoptosis in hepatocellular carcinoma. In Cancer cell international, 22, 278. doi:10.1186/s12935-022-02692-x. https://pubmed.ncbi.nlm.nih.gov/36068629/

3. Yu, ShanHai, Li, Wei, Liu, XiangDing, Liu, XiangYan, Zhang, Li-Wei. 2022. TRIM36 enhances lung adenocarcinoma radiosensitivity and inhibits tumorigenesis through promoting RAD51 ubiquitination and antagonizing hsa-miR-376a-5p. In Biochemical and biophysical research communications, 628, 1-10. doi:10.1016/j.bbrc.2022.08.053. https://pubmed.ncbi.nlm.nih.gov/36058131/

4. Zhao, Bin, Qiao, Gaofeng, Li, Jianhua, Zhang, Hua, Zhang, Lu. 2022. TRIM36 suppresses cell growth and promotes apoptosis in human esophageal squamous cell carcinoma cells by inhibiting Wnt/β-catenin signaling pathway. In Human cell, 35, 1487-1498. doi:10.1007/s13577-022-00737-x. https://pubmed.ncbi.nlm.nih.gov/35768649/

5. Zhao, Xusong, Zhou, Tianren, Wang, Yuhao, Li, Jie, Liang, Chao. 2023. Trigred motif 36 regulates neuroendocrine differentiation of prostate cancer via HK2 ubiquitination and GPx4 deficiency. In Cancer science, 114, 2445-2459. doi:10.1111/cas.15763. https://pubmed.ncbi.nlm.nih.gov/36799474/

6. Zhang, Jikai, Zou, Botao, Geng, Yunfeng, Lin, Xiaoman, Sun, Nan. 2025. TRIM36 serves as a prognostic indicator linked to immune infiltration in KIRC. In Heliyon, 11, e42540. doi:10.1016/j.heliyon.2025.e42540. https://pubmed.ncbi.nlm.nih.gov/40028597/