Penk, short for proenkephalin, is a gene that codes for a precursor peptide from which enkephalins (endogenous opioids) are cleaved. These enkephalins act on opioid receptors and are involved in various physiological processes. The gene is also associated with the PI3K/Akt signaling pathway [1]. PENK has potential significance in multiple biological contexts and diseases, making it an important target for functional studies.

In osteosarcoma, PENK was found to be downregulated in tumor samples compared to normal human osteoblasts. Silencing PENK in MG63 cells promoted cell migration, and this effect was partially attenuated by LY294002, indicating that PENK inhibits osteosarcoma cell migration by activating the PI3K/Akt signaling pathway [1].

In bladder cancer, the methylation status of PENK shows promise as a biomarker. Aberrant methylation sites of the PENK gene could potentially be used for early detection of bladder cancer, with a mePENK-qMSP test showing high sensitivity and specificity [2]. Also, a urine-based PENK methylation test (mePENK test) has good performance for detecting non-muscle-invasive bladder cancer recurrence, outperforming cytology and the NMP22 test [4].

In kidney-related research, PENK plasma concentration may accurately represent glomerular filtration rate in patients with sepsis or cardiac diseases. It is also associated with long-term outcomes in acute kidney injury and cardiac diseases [3]. PENK-A, expressed by renal proximal tubular epithelial cells, acts as a brake in kidney regeneration by inhibiting hydrogen peroxide production [5].

In conclusion, Penk has diverse functions in different biological processes and disease conditions. Its role in inhibiting osteosarcoma cell migration, its potential as a biomarker for bladder cancer detection and recurrence monitoring, and its significance in kidney function and regeneration highlight its importance. Studies on Penk, including those potentially using gene knockout or conditional knockout mouse models in the future, can further elucidate its functions and provide new insights into disease mechanisms and treatment strategies.

References:

1. Zhang, Hai-Ping, Yu, Zi-Liang, Wu, Bing-Bing, Sun, Fa-Rui. 2020. PENK inhibits osteosarcoma cell migration by activating the PI3K/Akt signaling pathway. In Journal of orthopaedic surgery and research, 15, 162. doi:10.1186/s13018-020-01679-6. https://pubmed.ncbi.nlm.nih.gov/32334633/

2. Oh, Tae Jeong, Lim, Eunkyung, Bang, Bo-Ram, Song, Ki Hak, An, Sungwhan. 2022. Identification and validation of methylated PENK gene for early detection of bladder cancer using urine DNA. In BMC cancer, 22, 1195. doi:10.1186/s12885-022-10275-2. https://pubmed.ncbi.nlm.nih.gov/36403035/

3. Beunders, Remi, Struck, Joachim, Wu, Alan H B, Jaffe, Allan, Pickkers, Peter. . Proenkephalin (PENK) as a Novel Biomarker for Kidney Function. In The journal of applied laboratory medicine, 2, 400-412. doi:10.1373/jalm.2017.023598. https://pubmed.ncbi.nlm.nih.gov/33636859/

4. Han, Hyunho, Oh, Tae Jeong, Heo, Ji Eun, An, Sungwhan, Choi, Young-Deuk. 2024. Clinical Validation of the Proenkephalin (PENK) Methylation Urine Test for Monitoring Recurrence of Non-muscle-invasive Bladder Cancer. In European urology open science, 62, 99-106. doi:10.1016/j.euros.2024.02.010. https://pubmed.ncbi.nlm.nih.gov/38496823/

5. Liu, Chi, Liu, Xiaoliang, He, Zhongwei, Huang, Yinghui, Zhao, Jinghong. 2023. Proenkephalin-A secreted by renal proximal tubules functions as a brake in kidney regeneration. In Nature communications, 14, 7167. doi:10.1038/s41467-023-42929-5. https://pubmed.ncbi.nlm.nih.gov/37935684/