Gas5, or growth arrest-specific transcript 5, is a long non-coding RNA (lncRNA) that lacks the ability to encode functional proteins despite having small open reading frames in its exons [6]. It is the host gene of several small nucleolar RNAs (snoRNAs) which are thought to suppress tumor progression by methylating ribosomal RNA (rRNA) [6]. Gas5 plays a crucial role in multiple signaling pathways, such as those related to miRNA, p53, mTOR, glucocorticoid response element (GRE), and AKT [1]. It is involved in regulating important cellular processes like cell proliferation, invasion, migration, and apoptosis, and has significant implications in various diseases including cancer and diabetes [1,3,4].

In cancer research, Gas5 has been identified as a tumor suppressor in many cancers. For example, in prostate cancer, it reduces cell proliferation and increases apoptosis, influencing cell cycle control via interactions with signaling pathways and microRNAs [2]. In breast cancer, it enhances apoptosis by regulating apoptotic proteins and can increase the sensitivity of breast cancer cells to chemotherapeutic agents. Low levels of Gas5 are associated with increased invasion, metastasis, and tumor aggressiveness [5].

In the nervous system, a study showed that Gas5 is a suppressor for axon regeneration. Inhibiting Gas5 expression promotes neurite growth of dorsal root ganglion (DRG) neurons in vitro, and Gas5 knockout (Gas5-/-) mice display enhanced nerve regeneration ability after sciatic nerve injury in vivo, indicating its role in axon regeneration in both the peripheral and central nervous systems [7].

In conclusion, Gas5 is a multifunctional lncRNA with key roles in regulating cellular processes and disease-related pathways. The use of gene knockout mouse models, such as the Gas5-/-mice, has provided valuable insights into its functions in cancer and nervous system-related diseases, highlighting its potential as a diagnostic biomarker and therapeutic target in these disease areas.