Dhrs4-flox Mouse

DHRS4, a gene within the human DHRS4 gene cluster which also includes DHRS4L2 and DHRS4L1, encodes an NADP(H)-dependent retinol dehydrogenase/reductase [9]. It has been implicated in various biological processes, and understanding its function is crucial for elucidating related physiological and pathological mechanisms.

In cancer research, DHRS4-AS1, an antisense lncRNA associated with DHRS4, has been extensively studied. In gastric cancer, its down-regulation is linked to tumor size, advanced stage, and vascular invasion. It inhibits cell proliferation and promotes apoptosis by destabilizing pro-oncogenic DHX9 and disrupting its association with ILF3 [1]. In hepatocellular carcinoma, DHRS4-AS1 is down-regulated, and its overexpression restrains cell proliferation, promotes apoptosis, and arrests the cell cycle in G0/G1 phase via the miR-522-3p/SOCS5 axis [2]. In NSCLC, DHRS4-AS1 suppresses cancer cell stemness by sponging miR-224-3p and upregulating TP53 and TET1 [3]. In endometriosis, DHRS4-AS1 inhibits ectopic endometrial cell proliferation, migration, and invasion by regulating miR-139-5p expression [6]. In thyroid cancer, DHRS4-AS1 acts as a miR-222-3p sponge, and its overexpression inhibits cell proliferation and promotes apoptosis [7]. In gliomas, miR-29a-5p suppresses cell proliferation, invasion, and migration by targeting DHRS4, suggesting DHRS4 may be an oncogene [8]. In ulcerative colitis, METTL14 regulates inflammation via the DHRS4-AS1/miR-206/A3AR axis, with METTL14 knockdown reducing DHRS4-AS1 expression [4]. In amyotrophic lateral sclerosis, Dhrs4 expression in the spinal cord is upregulated during disease progression, and its upregulation with DHRS3 may be associated with activation of the complement cascade in the immune system [5].

In conclusion, research on DHRS4 and its associated lncRNA DHRS4-AS1 has revealed their significant roles in multiple diseases, especially in cancer-related biological processes such as cell proliferation, apoptosis, and stemness, as well as in neurodegenerative and inflammatory diseases. These findings contribute to a better understanding of disease mechanisms and may offer potential therapeutic targets.