KLF2 transcription suppresses endometrial cancer cell proliferation, invasion, and migration through the inhibition of NPM1.

Endometrial cancer (EC) is the most common gynaecologic malignancy. This study was to explore the role of kruppel-like factor 2 (KLF2) in EC cell behaviours. The expression of KLF2 in EC and its correlation with NPM1 were first predicted on the database. Levels of KLF2 and nucleophosmin 1 (NPM1) in EC cell lines were then determined. After transfection of the overexpression vector of KLF2 or NPM1, cell proliferation, invasion, and migration were evaluated. The binding relationship between KLF2 and the NPM1 promoter was analysed. KLF2 was downregulated while NPM1 was upregulated in EC cells. KLF2 overexpression reduced the proliferation potential of EC cells and the number of invaded and migrated cells. KLF2 was enriched in the NPM1 promoter and inhibited NPM1 transcriptional level. NPM1 overexpression neutralised the effects of KLF2 overexpression on suppressing EC cell growth. Collectively, KLF2 was decreased in EC cells and KLF2 overexpression increased the binding to the NPM1 promoter to inhibit NPM1 transcription, thus suppressing EC cell growth.

What is already known on this subject? Endometrial cancer (EC) sees a significant increase in prevalence globally with poor survival rates. KLF2 has been recognised as a tumour suppressor in a variety of malignancies. NPM1 can regulate EC cell viability and apoptosis.What do the results of this study add? This study highlighted that KLF2 produces an anti-tumour effect in EC and KLF2 can regulate NPM1 expression in EC and thereafter affect the proliferative, migratory, and invasive abilities of EC cells.What are the implications of these findings for clinical practice and/or further research? KLF2 overexpression suppresses NPM1 transcription and inhibits EC cell growth. Targeting KLF2 overexpression may be useful for EC treatment in clinical practice.

High Expression of Circular RNA-Mitochondrial tRNA Translation Optimization 1 Assists the Diagnosis of High-Risk Human Papillomavirus Infection in Cervical Cancer.

OBJECTIVE: Persistence of high-risk human papillomavirus (HR-HPV) infection is a paramount determinant in cervical cancer (CC) development. Circular RNAs have the potential to be promising biomarkers for various cancers. This study explored circular RNA-mitochondrial tRNA translation optimization 1 (circMTO1) expression in the serum of CC patients and its clinical value in diagnosing CC and predicting HR-HPV infection. MATERIALS AND METHODS: In total, 125 CC patients (including 78 cases with HR-HPV) were enrolled, with another 76 healthy people as controls. Serum circMTO1 and miR-199a expressions were detected by reverse transcription-quantitative polymerase chain reaction, and the diagnostic efficacy of circMTO1 for CC and HR-HPV infection was analyzed by the receiver operating characteristic curve. According to the median of serum circMTO1 expression, CC patients were assigned into circMTO1 low/high expression groups to analyze the correlation between circMTO1 and clinical parameters using the Fisher and χ 2 tests. Independent association of circMTO1 with HR-HPV infection in CC was evaluated via logistics multivariate regression analysis. Targeted relationship between miR-199a and circMTO1 was predicted by Starbase Web site and validated via dual-luciferase assay, with their correlation further assessed by Pearson analysis. RESULTS: Serum circMTO1 was increased in CC patients and prominently elevated in HR-HPV-positive CC patients, with a level greater than 1.485 assisting CC diagnosis and a level greater than 2.480 assisting HR-HPV-positive diagnosis. The circMTO1 was interrelated to clinical stage, tumor differentiation, lymph node metastasis, invasion depth, and independently linked with HR-HPV infection in CC. Serum miR-199a was downregulated in HR-HPV-positive CC patients and inversely correlated with circMTO1. CONCLUSIONS: Serum circMTO1 is upregulated in HR-HPV-positive CC patients and has a diagnostic value for HR-HPV infection in CC.