Sstr5, short for somatostatin receptor 5, is one of the five somatostatin receptor subtypes. Somatostatin acts on these receptors to inhibit endocrine and exocrine secretion in various tissues. Sstr5 is involved in multiple biological processes. For example, it is part of the SSTR5-Notch-Hes1-MUC2 signaling pathway, through which somatostatin can stimulate colonic MUC2 expression and mucus secretion, playing a role in colonic mucus barrier regulation [3].

Research on Sstr5-related long non-coding RNA (lncRNA) SSTR5-AS1 has shown significant findings. In esophageal cancer (ESCA), increased SSTR5-AS1 expression was associated with poor prognosis, and its knockdown inhibited ESCA cell proliferation [1]. Similar results were seen in prostate cancer (PCa), where SSTR5-AS1 promoted cell proliferation, migration, and invasion [2]. In gallbladder carcinoma, SSTR5-AS1 facilitated gemcitabine resistance via stabilizing NONO [4]. In gastric cancer, high SSTR5-AS1 expression was related to advanced pathologic stage, distant metastasis, and poor overall and disease-free survival [6]. Also, in a phase I study, an oral SSTR5 antagonist SCO-240 was shown to be safe, well-tolerated, and could stimulate growth hormone secretion, suggesting potential for GH-related disorders treatment [5].

In conclusion, Sstr5 and its associated lncRNA SSTR5-AS1 play important roles in various biological functions and disease processes. The research on SSTR5-AS1 in different cancers highlights its potential as a prognostic biomarker and therapeutic target. The study of Sstr5-targeted agents like SCO-240 also provides new treatment possibilities for related diseases.

References:

1. Hu, Yuhao, Mao, Ning, Zheng, Wei, Hong, Bin, Deng, Xiong. 2023. lncRNA SSTR5-AS1 Predicts Poor Prognosis and Contributes to the Progression of Esophageal Cancer. In Disease markers, 2023, 5025868. doi:10.1155/2023/5025868. https://pubmed.ncbi.nlm.nih.gov/36726845/

2. Yuan, Shuai, Bi, Jianlong, Zhang, Yangang. . LncRNA SSTR5-AS1 as a Prognostic Marker Promotes Cell Proliferation and Epithelial-to-Mesenchymal Transition in Prostate Cancer. In Critical reviews in eukaryotic gene expression, 33, 1-12. doi:10.1615/CritRevEukaryotGeneExpr.2022042183. https://pubmed.ncbi.nlm.nih.gov/36734853/

3. Song, Shuailing, Li, Xiao, Geng, Chong, Li, Yanni, Wang, Chunhui. 2019. Somatostatin stimulates colonic MUC2 expression through SSTR5-Notch-Hes1 signaling pathway. In Biochemical and biophysical research communications, 521, 1070-1076. doi:10.1016/j.bbrc.2019.11.034. https://pubmed.ncbi.nlm.nih.gov/31733832/

4. Xue, Zhuowei, Yang, Bikang, Xu, Qinyang, Zhu, Xiaolu, Qin, Guangyi. 2019. Long non-coding RNA SSTR5-AS1 facilitates gemcitabine resistance via stabilizing NONO in gallbladder carcinoma. In Biochemical and biophysical research communications, 522, 952-959. doi:10.1016/j.bbrc.2019.10.104. https://pubmed.ncbi.nlm.nih.gov/31810606/

5. Nishizaki, Harunobu, Kagawa, Tomoya, Sugama, Jun, Moritoh, Yusuke, Watanabe, Masanori. 2024. Oral SSTR5 Antagonist SCO-240 for Growth Hormone Stimulation: A Phase I Single-Dose Study in Healthy Individuals. In Clinical pharmacology and therapeutics, 115, 1326-1335. doi:10.1002/cpt.3212. https://pubmed.ncbi.nlm.nih.gov/38549435/

6. Cheng, Y, Di, J, Wu, J, Zhang, Y, Xie, D-H. . Diagnostic and prognostic significance of long noncoding RNA SSTR5-AS1 in patients with gastric cancer. In European review for medical and pharmacological sciences, 24, 5385-5390. doi:10.26355/eurrev_202005_21322. https://pubmed.ncbi.nlm.nih.gov/32495873/