miR‐145 inhibits glutamine metabolism through c‐myc/GLS1 pathways in ovarian cancer cells

Abstract

miR‐145 has been found to be a participant in cancer metastasis and glucose metabolism in ovarian cancer. However, the role of glutamine metabolism in ovarian cancer remains unclear. In this study, we aim to elucidate the molecular mechanism underlying the regulation of glutamine metabolism by miR‐145 in ovarian cancer cells. The messenger RNA (mRNA) levels of miR‐145 and glutaminase 1 (GLS1) were examined by quantitative real‐time polymerase chain reaction (qRT‐PCR). The protein levels of c‐myc and GLS1 were detected by western blot analysis. Luciferase reporter assays were used to validate c‐myc was a target of miR‐145. Glutamine metabolism was analyzed using assay kits. In addition, we performed luciferase reporter assays and chromatin immunoprecipitation assay to validate c‐myc transcription activated GLS1 and promoted GLS1 expression. The qRT‐PCR demonstrated that the mRNA level of miR‐145 and GLS1 was negatively correlated in ovarian cancer tissues and cell lines. Kaplan–Meier survival analysis and the log‐rank test showed that patients with high miR‐145 expression had significantly increased the overall survival. The overexpression of miR‐145 inhibited glutamine consumption, α‐ketoglutarate production, and cellular ATP levels. Furthermore, we found miR‐145 inhibited glutamine metabolism by targeting c‐myc. Moreover, c‐myc could promote GLS1 expression by transcription activated. Together, our results revealed that miR‐145 inhibited glutamine metabolism through c‐myc/GLS1 pathways in ovarian cancer cells, which may improve the current strategy of ovarian cancer diagnosis and therapy.

The Significance of MicroRNAs Expression in Regulation of Extracellular Matrix and Other Drug Resistant Genes in Drug Resistant Ovarian Cancer Cell Lines

“…The upregulation of miR-145 was also discovered to be connected with strong downregulation of the Myc proto-oncogene protein in W1PR1 cell lines. miR-145 was described as a suppressor miRNA that directly targets the MYC transcript in esophageal squamous cell carcinoma [94] and ovarian cancer [95]. Moreover, as our analysis shows, the MYC downregulation can be due to let-7c upregulation in this cell line as well, which was described previously in prostate cancer cells [96].…”

YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells

“…Many recent studies have found that microRNA is closely related to ovarian cancer [27,28]. Previous studies con rmed that miR-145 regulated different biological functions of ovarian cancer by targeting different target genes [17][18][19][20]. However, the expression pattern and the m6A-regulated role of miR-145 in ovarian cancer were still unclear.…”

“…MiR-145 has different regulatory genes in different tumors; the molecular mechanisms of tumor suppressors are also different. Previous studies con rmed that miR-145 could regulate different biological functions of ovarian cancer by targeting different target genes [17][18][19][20].…”

The significance of microRNA genes expression in ovarian cancer cell lines resistant to cytotoxic drugs

“…The upregulation of miR-145 was also discovered as connected with strong downregulation of Myc Proto-Oncogene Protein in W1PR1 cell lines. miR-145 has been described as a suppressor miRNA that directly target MYC transcript in esophageal squamous cell carcinoma [99] and ovarian cancer [100].…”