Gas5, or growth arrest-specific transcript 5, is a long non-coding RNA (lncRNA). It doesn't encode functional proteins but contains small open reading frames (ORFs) in its exon sequence and is the host gene of several small nucleolar RNAs (snoRNAs). Gas5 is highly expressed during cell cycle arrest but downregulated in actively growing cells. It plays a crucial role in multiple signaling pathways such as miRNA, p53, mTOR, glucocorticoid response element (GRE), and AKT, regulating complex intracellular signaling mainly through signal, decoy, and guide mechanisms [1]. It is also associated with various biological processes like cell proliferation, invasion, migration, apoptosis, and has shown significance in diseases such as cancer, diabetes, bone diseases, and cardiovascular diseases [1-10].

In cancer, Gas5 acts as a tumor suppressor in many types including prostate, breast, and most solid tumors by reducing cell proliferation and increasing apoptosis [2,3,5,6]. For example, 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 prostate cancer, its expression is related to clinicopathological characteristics, making it a promising biomarker for disease classification and individualized treatment [2]. In diabetes, Gas5 influences insulin signaling pathways, glucose metabolism, and β-cell function, playing a role in hyperglycemia and insulin resistance [4].

In conclusion, Gas5 is a key lncRNA involved in multiple biological functions and diseases. Its role as a tumor suppressor in cancer and its involvement in diabetes-related processes are well-documented. Research on Gas5, including through gene knockout or conditional knockout mouse models (not explicitly detailed in provided references but a common approach in lncRNA functional studies), could further clarify its mechanisms, potentially leading to new diagnostic and therapeutic strategies for these diseases.

References:

1. Zhou, Yang, Chen, Binghai. 2020. GAS5‑mediated regulation of cell signaling (Review). In Molecular medicine reports, 22, 3049-3056. doi:10.3892/mmr.2020.11435. https://pubmed.ncbi.nlm.nih.gov/32945519/

2. Alharbi, Khalid Saad. 2023. Exploring GAS5's impact on prostate cancer: Recent discoveries and emerging paradigms. In Pathology, research and practice, 251, 154851. doi:10.1016/j.prp.2023.154851. https://pubmed.ncbi.nlm.nih.gov/37837861/

3. Kaur, Jesminder, Salehen, Nur'ain, Norazit, Anwar, Rahman, Nik Mohd Afizan Nik Abd, Ibrahim, Kamariah. 2022. Tumor Suppressive Effects of GAS5 in Cancer Cells. In Non-coding RNA, 8, . doi:10.3390/ncrna8030039. https://pubmed.ncbi.nlm.nih.gov/35736636/

4. Alharbi, Khalid Saad. 2023. GAS5: A pivotal lncRNA in diabetes mellitus pathogenesis and management. In Pathology, research and practice, 253, 154955. doi:10.1016/j.prp.2023.154955. https://pubmed.ncbi.nlm.nih.gov/38016351/

5. Thangavelu, Lakshmi, Moglad, Ehssan, Gupta, Gaurav, Sivaprasad, G V, Deorari, Mahamedha. 2024. GAS5 lncRNA: A biomarker and therapeutic target in breast cancer. In Pathology, research and practice, 260, 155424. doi:10.1016/j.prp.2024.155424. https://pubmed.ncbi.nlm.nih.gov/38909406/

6. Filippova, Elena A, Fridman, Marina V, Burdennyy, Alexey M, Dmitriev, Alexey A, Braga, Eleonora A. 2021. Long Noncoding RNA GAS5 in Breast Cancer: Epigenetic Mechanisms and Biological Functions. In International journal of molecular sciences, 22, . doi:10.3390/ijms22136810. https://pubmed.ncbi.nlm.nih.gov/34202777/