RIOK1, short for RIO Kinase 1, is a protein kinase/ATPase that plays a key role in regulating translation and ribosome assembly [5]. It is associated with multiple signaling pathways and is of great biological importance, especially in the context of various malignancies. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, could potentially be valuable for further studying its functions.

In colorectal cancer, blockade of RIOK1 using an inhibitor or by knocking down its expression decreased the resistance of CRC cells to radiotherapy both in vitro and in vivo. RIOK1 was found to regulate radioresistance by suppressing the p53 signaling pathway, phosphorylating G3BP2 at Thr226, which increased G3BP2 activity and facilitated p53 ubiquitination by MDM2 [1]. In non-small cell lung cancer, knockdown of RIOK1 inhibited cell proliferation, migration, invasion, and tumorigenesis in vivo through AKT, Cyclin B1, MMP2, and EMT pathways, and also increased apoptosis when treated with cisplatin [3]. In epithelial ovarian cancer, disruption of the SPC25/RIOK1/MYH9 trimeric complex attenuated cancer stem cell phenotypes and enhanced platinum efficacy [2]. In glioma, silencing RIOK1 inhibited the proliferation, migration, and invasion of glioma cell lines by suppressing AKT and c-Myc expression [4]. In hepatocellular carcinoma, RIOK1 knockdown suppressed cell proliferation, survival, and tumor growth in vivo, while overexpression enhanced these oncogenic phenotypes, and it may promote cell proliferation by affecting the cell cycle and DNA repair pathways [5].

In conclusion, RIOK1 is a significant player in multiple cancer-related biological processes. Model-based research, especially KO/CKO mouse models if available, could potentially further clarify its role in these diseases. The studies on RIOK1 provide potential diagnostic and therapeutic targets for various cancers such as colorectal, lung, ovarian, glioma, and hepatocellular carcinoma.

References:

1. Chen, Yaqi, Zhou, Sha, Wan, Kairui, Hu, Junbo, Hou, Zhenlin. 2022. RIOK1 mediates p53 degradation and radioresistance in colorectal cancer through phosphorylation of G3BP2. In Oncogene, 41, 3433-3444. doi:10.1038/s41388-022-02352-4. https://pubmed.ncbi.nlm.nih.gov/35589951/

2. Jiang, Xingyu, Yang, Muwen, Zhang, Weijing, Zhang, Yanna, Song, Libing. 2024. Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2406688. doi:10.1002/advs.202406688. https://pubmed.ncbi.nlm.nih.gov/39488790/

3. Wang, Rong, Chai, Wen-Shu, Pan, Dian-Zhu, He, Yu-Hai, Pan, Shuang. 2022. RIOK1 is associated with non-small cell lung cancer clinical characters and contributes to cancer progression. In Journal of Cancer, 13, 1289-1298. doi:10.7150/jca.64668. https://pubmed.ncbi.nlm.nih.gov/35281872/

4. Wang, Yiwei, Xie, Xiaochen, Li, Shu, Zhang, Min, Zhang, Zhong. 2021. Co-overexpression of RIOK1 and AKT1 as a prognostic risk factor in glioma. In Journal of Cancer, 12, 5745-5752. doi:10.7150/jca.60596. https://pubmed.ncbi.nlm.nih.gov/34475988/

5. Ruan, Chunyan, Shang, Tianyu, Zhang, Sijia, Yang, Yuefeng, Shen, Yi. . RIOK1: A Novel Oncogenic Driver in Hepatocellular Carcinoma. In Cancer medicine, 14, e70597. doi:10.1002/cam4.70597. https://pubmed.ncbi.nlm.nih.gov/39865406/