PIMREG, also known as phosphatidylinositol binding clathrin assembly protein interacting mitotic regulator, is a mitotic regulator essential to the metaphase-to-anaphase transition in the cell cycle [2]. It localizes to the nucleus and can elevate the nuclear localization of clathrin assembly lymphomedullary leukocythemia gene [9]. PIMREG is involved in multiple biological processes such as cell proliferation, and is associated with pathways like cell cycle, DNA damage response, and immune-related pathways [1,2,5,9].

In glioblastoma, PIMREG expression strongly correlates with cellular proliferation. Its silencing renders glioblastoma cells sensitive to temozolomide treatment and affects ATR-and ATM-dependent signaling, indicating its role in DNA damage response and temozolomide resistance [1]. In clear cell renal cell carcinoma (ccRCC), knockdown of PIMREG significantly inhibits cell proliferation, migration and invasion, and reduces the expression of cyclin D1, CDK4 and CDK6, suggesting its importance in ccRCC development [2]. In breast cancer, high expression of PIMREG is associated with poor prognosis, and its knockdown can inhibit cell proliferation and migration [3]. In glioma, PIMREG overexpression is related to poor prognosis, immune cell infiltrates and responses to immunotherapy. It also promotes glioma cell proliferation, migration and invasion by activating the β-catenin pathway [4,8]. In cholangiocarcinoma, PIMREG facilitates cell growth, invasion and migration by regulating cell-cycle-related biomarkers [5]. In hepatocellular carcinoma, HOXB13 promotes HCC progression and drug resistance through up-regulating PIMREG transcription, which in turn affects cell cycle and DNA repair [6]. In lung adenocarcinoma, high PIMREG expression predicts poor survival outcomes and is correlated with immune infiltrates [7].

In conclusion, PIMREG plays a crucial role in cell proliferation, cell cycle regulation, DNA damage response, and is associated with immune-related processes. Studies using loss-of-function approaches in various cancer cell lines have revealed its significant impact on the development and progression of multiple cancers including glioblastoma, ccRCC, breast cancer, glioma, cholangiocarcinoma, hepatocellular carcinoma, and lung adenocarcinoma. Understanding PIMREG's functions can potentially provide new therapeutic targets for these diseases.

References:

1. Serafim, Rodolfo Bortolozo, Cardoso, Cibele, Arfelli, Vanessa Cristina, Valente, Valeria, Archangelo, Leticia Fröhlich. 2022. PIMREG expression level predicts glioblastoma patient survival and affects temozolomide resistance and DNA damage response. In Biochimica et biophysica acta. Molecular basis of disease, 1868, 166382. doi:10.1016/j.bbadis.2022.166382. https://pubmed.ncbi.nlm.nih.gov/35301087/

2. Yao, Huibao, Lyu, Feifei, Ma, Jian, Wu, Jitao, Zhou, Zhongbao. 2023. PIMREG is a prognostic biomarker involved in immune microenvironment of clear cell renal cell carcinoma and associated with the transition from G1 phase to S phase. In Frontiers in oncology, 13, 1035321. doi:10.3389/fonc.2023.1035321. https://pubmed.ncbi.nlm.nih.gov/36776322/

3. Zhao, Wenjing, Chang, Yuanjin, Wu, Zhaoye, Sun, Chenyu, Gao, Ju. 2023. Identification of PIMREG as a novel prognostic signature in breast cancer via integrated bioinformatics analysis and experimental validation. In PeerJ, 11, e15703. doi:10.7717/peerj.15703. https://pubmed.ncbi.nlm.nih.gov/37483962/

4. Zhu, Hua, Hu, Xinyao, Feng, Shi, Zou, Ning, Xiong, Xiaoxing. 2022. Predictive value of PIMREG in the prognosis and response to immune checkpoint blockade of glioma patients. In Frontiers in immunology, 13, 946692. doi:10.3389/fimmu.2022.946692. https://pubmed.ncbi.nlm.nih.gov/35928818/

5. Jiang, Zhao-Ming, Li, Hong-Bin, Chen, Shu-Guo. . PIMREG, a Marker of Proliferation, Facilitates Aggressive Development of Cholangiocarcinoma Cells Partly Through Regulating Cell Cycle-Related Markers. In Technology in cancer research & treatment, 19, 1533033820979681. doi:10.1177/1533033820979681. https://pubmed.ncbi.nlm.nih.gov/33356974/

6. Tang, Cui, Qiu, Shixiong, Mou, Wenying, Xu, Jinming, Wang, Peijun. 2022. Excessive activation of HOXB13/PIMREG axis promotes hepatocellular carcinoma progression and drug resistance. In Biochemical and biophysical research communications, 623, 81-88. doi:10.1016/j.bbrc.2022.07.066. https://pubmed.ncbi.nlm.nih.gov/35878427/

7. Jiang, Feng, Liang, Min, Huang, Xiaolu, Shi, Wenjing, Wang, Yumin. 2021. High expression of PIMREG predicts poor survival outcomes and is correlated with immune infiltrates in lung adenocarcinoma. In PeerJ, 9, e11697. doi:10.7717/peerj.11697. https://pubmed.ncbi.nlm.nih.gov/34268011/

8. Wang, Dekang, Hu, Aili, Peng, Hao, Li, Dongbo, Zhang, Li. 2021. Tumor-promoting function of PIMREG in glioma by activating the β-catenin pathway. In 3 Biotech, 11, 380. doi:10.1007/s13205-021-02922-5. https://pubmed.ncbi.nlm.nih.gov/34458056/

9. Zhu, Hua, Hu, Xinyao, Ye, Yingze, Gu, Lijuan, Xiong, Xiaoxing. 2021. Pan-Cancer Analysis of PIMREG as a Biomarker for the Prognostic and Immunological Role. In Frontiers in genetics, 12, 687778. doi:10.3389/fgene.2021.687778. https://pubmed.ncbi.nlm.nih.gov/34594356/