DHRS4, also known as dehydrogenase/reductase 4, encodes a NADP(H)-dependent retinol dehydrogenase/reductase enzyme [9]. It is part of a gene cluster including DHRS4L2 and DHRS4L1, and the genes in this cluster may be transcriptionally regulated through antisense transcription mechanisms [9]. DHRS4 enzymes share common sequence motives related to coenzyme binding and catalytic mechanism with its paralogue DHRS2, but have different substrate-binding sequences [8].

In various diseases, DHRS4-AS1, an antisense long non-coding RNA of DHRS4, has shown significant effects. In gastric cancer, it inhibits cell proliferation and promotes apoptosis by destabilizing pro-oncogenic DHX9 and inhibiting the association between DHX9 and ILF3 [1]. In hepatocellular carcinoma, it suppresses proliferation and promotes apoptosis via the miR-522-3p/SOCS5 axis [2]. In NSCLC, it inhibits the stemness of cancer cells by sponging miR-224-3p and upregulating TP53 and TET1 [3]. In endometriosis, it inhibits ectopic endometrial cell proliferation, migration, and invasion by regulating miR-139-5p expression [5]. In thyroid cancer, it may act as a diagnostic factor by sponging miR-222-3p and regulating cancer cell proliferation and apoptosis [6]. In ulcerative colitis, METTL14-regulated DHRS4-AS1 mitigates inflammatory injury via the miR-206/A3AR axis [4]. In gliomas, miR-29a-5p suppresses cell proliferation, invasion, and migration by targeting DHRS4, suggesting DHRS4 may be an oncogene [7].

In conclusion, studies related to DHRS4 and its associated non-coding RNA DHRS4-AS1 have revealed their important roles in multiple disease processes such as cancer and inflammatory diseases. These findings help in understanding the molecular mechanisms underlying these diseases and may potentially provide new therapeutic targets and diagnostic biomarkers.

References:

1. Xiao, Lei, Zhang, Yang, Luo, Qingqing, Chen, Zihua, Lai, Chen. 2023. DHRS4-AS1 regulate gastric cancer apoptosis and cell proliferation by destabilizing DHX9 and inhibited the association between DHX9 and ILF3. In Cancer cell international, 23, 304. doi:10.1186/s12935-023-03151-x. https://pubmed.ncbi.nlm.nih.gov/38041141/

2. Zhou, Yongping, Li, Kuan, Zou, Xuexia, Chen, Fangming, Dai, Tu. . LncRNA DHRS4-AS1 ameliorates hepatocellular carcinoma by suppressing proliferation and promoting apoptosis via miR-522-3p/SOCS5 axis. In Bioengineered, 12, 10862-10877. doi:10.1080/21655979.2021.1994719. https://pubmed.ncbi.nlm.nih.gov/34666613/

3. Yan, Fei, Zhao, Wei, Xu, Xiaoyue, Shi, Lin, Wu, Yuan. 2020. LncRNA DHRS4-AS1 Inhibits the Stemness of NSCLC Cells by Sponging miR-224-3p and Upregulating TP53 and TET1. In Frontiers in cell and developmental biology, 8, 585251. doi:10.3389/fcell.2020.585251. https://pubmed.ncbi.nlm.nih.gov/33425890/

4. Wu, Weiyun, Li, Xiaowen, Zhou, Zhuliang, Ye, Shicai, Quan, Juan-Hua. 2024. METTL14 regulates inflammation in ulcerative colitis via the lncRNA DHRS4-AS1/miR-206/A3AR axis. In Cell biology and toxicology, 40, 95. doi:10.1007/s10565-024-09944-8. https://pubmed.ncbi.nlm.nih.gov/39528760/

5. Cui, Xuan, Zhou, Shisan, Lin, Yongtao. . Long non-coding RNA DHRS4 antisense RNA 1 inhibits ectopic endometrial cell proliferation, migration, and invasion in endometriosis by regulating microRNA-139-5p expression. In Bioengineered, 13, 9792-9804. doi:10.1080/21655979.2022.2060781. https://pubmed.ncbi.nlm.nih.gov/35414313/

6. Xu, Shuai, Zheng, Xinyi, Wu, Haibin, Liu, Qianqian, Ye, Ren-Qun. 2024. Feasibility study of lncRNA DHRS4-AS1 sponge miR-222-3p in the diagnosis of thyroid cancer. In Endokrynologia Polska, 75, 494-500. doi:10.5603/ep.99456. https://pubmed.ncbi.nlm.nih.gov/39376175/

7. Dai, Yong, Chen, Zhenhua, Zhao, Wei, Hu, Hongkang, Zhang, Yi. 2020. miR-29a-5p Regulates the Proliferation, Invasion, and Migration of Gliomas by Targeting DHRS4. In Frontiers in oncology, 10, 1772. doi:10.3389/fonc.2020.01772. https://pubmed.ncbi.nlm.nih.gov/33014873/

8. Gabrielli, Franco, Tofanelli, Sergio. 2012. Molecular and functional evolution of human DHRS2 and DHRS4 duplicated genes. In Gene, 511, 461-9. doi:10.1016/j.gene.2012.09.013. https://pubmed.ncbi.nlm.nih.gov/23036705/

9. Su, Zhong-Jing, Zhang, Qiao-Xia, Liu, Ge-Fei, Sui, Xu-Xia, Huang, Dong-Yang. 2010. Bioinformatic analysis of the human DHRS4 gene cluster and a proposed mechanism for its transcriptional regulation. In BMC molecular biology, 11, 43. doi:10.1186/1471-2199-11-43. https://pubmed.ncbi.nlm.nih.gov/20525226/