TRMT6 is Suppressed by miR-191-5p and Functions as a Tumor Promoter in Ovarian Cancer

Abstract

Ovarian cancer has a high mortality, and RNA methylation plays a role in several cancers. Our study aimed to explore the effects of differential expression of TRMT6, an N1-methyladenosine writer, on ovarian cancer and its upstream regulatory mechanism. Preliminary bioinformatics analysis revealed that TRMT6 was differentially expressed in ovarian cancer and normal ovarian tissues. Patients with ovarian cancer and high TRMT6 expression had a poor prognosis, and the area under the receiver operating characteristic curve was 0.759. This finding suggests that TRMT6 may be used as a biomarker for ovarian cancer. We used immunohistochemistry to verify the differential expression of TRMT6 in ovarian cancer and normal ovarian tissues. The differential expression of TRMT6 in ovarian cancer cell lines A2780 and OVCAR3 was confirmed using qPCR and western blotting. CCK-8, transwell assay results suggested that overexpression of TRMT6 promoted the proliferation and migration of ovarian cancer cells, whereas overexpression of miR-191-5p reduced these effects. Results of dual-luciferase reporter gene assays indicated that TRMT6 was the target gene of miR-191-5p. In conclusion, TRMT6 promoted the proliferation and migration of ovarian cancer cells, and its upstream miR-191-5p targeted and regulated TRMT6 to reduce these effects. TRMT6 gene expression may be used as a prognostic biomarker and its regulation as a therapeutic target in ovarian cancer.

Research progress of N1-methyladenosine RNA modification in cancer

“…Jiang Zhao et al demonstrated that high TRMT6 expression in patients with ovarian cancer correlates with poor prognoses compared to those with low TRMT6 expression. The adverse effects of high TRMT6 expression can be mitigated through targeted regulation of TRMT6 by upstream miR-191-5p [70]. MicroRNAs (miRNAs) serve as regulatory factors that inhibit translation and protein expression by binding to mRNA.…”

“…Among miRNAs, miR-191-5p exerts a regulatory function in various other cancers, demonstrating distinct roles in different contexts. For instance, it has been implicated in the suppression of miRNA expression in gastric cancer, renal epithelial cancer, and other malignancies, while promoting osteosarcoma development through the targeting of Recombinant Early Growth Response Protein 1(EGR1) [70][71][72][73].…”