miRNA-576-5p promotes endometrial cancer cell growth and metastasis by targeting ZBTB4

Abstract

Purpose MicroRNAs (miRNAs) have already been shown to have a strong correlation with the invasion and metastasis capacity of tumor cells. The present research examined the function of miRNA-576-5p (miR-576-5p) in the development of endometrial cancer (EC). Methods miR-576-5p and ZBTB4 expression in EC and benign endometrial tissues was measured using quantitative real-time PCR (qRT-PCR) and western blot. To evaluate the proliferation ability of tumor cells in vitro, 2,5-diphenyl-2H-tetrazolium bromide (MTT) and colony formation assays were carried out. The effect of miR-576-5p on the proliferation ability of EC cells in vivo was measured by the tumor formation in nude mice. The migration and invasion ability of tumor cells was determined using the transwell assay. To confirm the association between expressions of miR-576-5p and zinc finger and BTB domain containing four (ZBTB4), western blot, qRT-PCR, and luciferase assay were carried out. Results miR-576-5p expression increased significantly in EC samples than in benign endometrial tissues. The level of miR-576-5p was significantly higher in the polymerase ε (POLE) ultramutated subgroup compared to the other three subgroups. High levels of miR-576-5p expression were linked to a shorter progression-free interval time in the copy number high subgroup. Furthermore, upregulated miR-576-5p facilitated EC cell invasion and migration in vitro and promoted the proliferation of EC tumor cell lines both in vitro and in vivo. Moreover, this study showed that the expression of ZBTB4 decreased in patients with EC, and the dual-luciferase reporter assay confirmed that miR-576-5p binds directly to the 3′-UTR of ZBTB4 and inhibits the expression of ZBTB4. An increase in miR-576-5p expression leads to a decrease in the mRNA and protein expression level of ZBTB4. The effects of miR-576-5p can be reversed by overexpression of ZBTB4. Conclusion miR-576-5p promoted proliferation and metastasis capacity of EC cells by inhibiting ZBTB4 expression. We hypothesized that miR-576-5p could be a prospective therapeutic target for EC.

Plasma miRNA expression in patients with genetically confirmed multiple endocrine neoplasia type 1 syndrome and its phenocopies

“…В тканях аденокарциномы толстого кишечника была также выявлена усиленная экспрессия miR-576-5p, которая заметно способствовала пролиферации, миграции и инвазии клеток через регулятор роста нейронов 1 (NEGR1), который может являться основной терапевтической мишенью при аденокарциноме толстого кишечника [ 81 ]. Также повышенная экспрессия miR-576-5p была выявлена при раке эндометрия [ 82 ], где miR-576-5p способствовала пролиферации и метастазированию клеток рака эндометрия путем ингибирования экспрессии ZBTB4.…”

“…Промотор канцерогенеза [80] Cr толстого кишечника (↑) [81] Cr эндометрия (↑) [82] Примечание: Cr -карцинома; ПЖ -поджелудочная железа; МЖ -молочная железа; ГЦК -гепатоцеллюлярная карцинома; ПРЩЖ -папиллярный рак щитовидной железы; (↓) -сниженная экспрессия; (↑) -повышенная экспрессия.…”

Metformin inhibits ovarian granular cell pyroptosis through the miR-670-3p/NOX2/ROS pathway

“…3’UTR luciferase reporter assays were conducted as described previously [ 14 ]. Briefly, the 3’UTR of CYBB, including the wild-type (WT) or mutant-type (Mut) binding sites, was cloned downstream of the Renilla psiCHECK2 vector.…”

MicroRNAs as Potential Biomarkers in Gynecological Cancers

“…Increasing the expression of ZBTB4 inhibited the process of cell proliferation, colony formation and metastasis, while reducing the expression induced cell proliferation, colony formation and metastasis. Thus, it was concluded that miR-576-5p may regulate the development of tumor cells in endometrial cancer by targeting ZBTB4 [ 88 ].…”