Abstract
BackgroundSmall nucleolar RNA host gene 25 (SNHG25), a long noncoding RNA, has been well-studied in epithelial ovarian cancer. However, the specific functions of SNHG25 in endometrial cancer (EC) have not been studied yet. In this study, we aimed to elucidate the clinical significance of SNHG25 in EC and determine the regulatory activity of SNHG25 on the tumor-associated EC phenotype. We also thoroughly explored the molecular mechanisms underlying SNHG25 function in EC.MethodsGene expression was measured using quantitative real-time polymerase chain reaction. The detailed functions of SNHG25 in EC were examined by performing loss-of-function experiments. Moreover, the regulatory mechanisms involving SNHG25, microRNA-497-5p, and fatty acid synthase (FASN) were unveiled using the luciferase reporter assay and RNA immunoprecipitation.ResultsWe observed a high level of SNHG25 in EC using the TCGA dataset and our study cohort. Patients with a high SNHG25 level had shorter overall survival than those with a low SNHG25 level. SNHG25 deficiency resulted in tumor-repressing activities in EC cells by decreasing cell proliferation, migration, and invasion and promoting cell apoptosis. Furthermore, the function of SNHG25 depletion in impairing tumor growth in vivo was confirmed. SNHG25 sequestered miR-497-5p as a competing endogenous RNA in EC and consequently positively regulated FASN expression. Thus, the decrease in miR-497-5p or increase in FASN could neutralize the modulatory actions of SNHG25 knockdown in EC cells.ConclusionsThe depletion of SNHG25 impedes the oncogenicity of EC by targeting the miR-497-5p/FASN axis. The newly elucidated SNHG25/miR-497-5p/FASN pathway may be a promising target for the molecular-targeted management of EC.
Highlights
Small nucleolar RNA host gene 25 (SNHG25), a long noncoding RNA, has been well-studied in epithelial ovarian cancer
The SNHG25 level was increased in uterine corpus endometrial carcinoma tissues compared with normal tissues (Fig. 1B)
Si-SNHG25#1 and si-SNHG25#2 demonstrated relatively higher transfection efficacies (Fig. 2B), and these two small interfering RNA (siRNA) were used in the subsequent assays
Summary
Small nucleolar RNA host gene 25 (SNHG25), a long noncoding RNA, has been well-studied in epithelial ovarian cancer. The specific functions of SNHG25 in endometrial cancer (EC) have not been studied yet. 380,000 EC cases are recorded annually, with 89,000 mortalities globally. He et al Journal of Ovarian Research (2021) 14:163. At present, owing to the substantial improvements in therapeutic techniques, patients with EC usually achieve favorable outcomes, with the 5-year survival rate of approximately 85% [4]. A large number of patients with EC are diagnosed at the advanced stage at the time of symptom onset, and these therapeutic interventions are not effective for such patients, resulting in the 5-year survival rate to decrease to < 20% [5]. More knowledge of EC onset and progression at the molecular level may play a key role in devising treatment strategies for EC and achieving better therapeutic efficacy
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