ATF1 regulates MAL2 expression through inhibition of miR-630 to mediate the EMT process that promotes cervical cancer cell development and metastasis

다국어 초록 (Multilingual Abstract)

Objective: The existence of activating transcription factor 1 (ATF1) could be employedas a clinical marker in the context of cer vical cancer development, although its specificmechanism has not been fully clarified.
Methods: To evaluate the presence of ATF1, miR-630, and myelin and lymphocyte protein 2(MAL2) in cer vical malignancies, we conducted quantitative reverse transcription polymerasechain reaction, immunohistochemistr y, and Western blot assays; further studied theexpansion, migration, invasion and epithelial-mesenchymal transition (EMT) of cer vicalcarcinoma cells using colony formation assay, transwell, loss cytometr y, Western blot.
Chromatin immunoprecipitation (ChIP) and RNA immunoprecipitation (RIP) were used toverif y that ATF1 could directly transcriptionally repress miR-630; dual luciferase reporterassay and RIP assay were employed to confirm that miR-630 targeted to repress MAL2.
Results: In cer vical cancer cases, elevated ATF1 expression and reduced miR-630 expressionwere detected, displaying a negative relationship between them. Inhibition of ATF1 hinderedthe growth, migration, infiltration, and EMT in cer vical carcinoma cells, while upregulationof miR-630 mitigated the aggressive characteristics of these cells. ATF1 was found totranscriptionally repress miR-630 by TransmiR and ALGGEN prediction and ChIP validation.
MicroRNA modulates gene expression and affects cancer progression, and we discovered thatmiR-630 regulates cancer progression by targeting and inhibiting MAL2.
Conclusion: ATF1, which modulates the miR-630/MAL2 pathway, affects the EMT processand cer vical carcinoma cell growth and spread. Therefore, ATF1 may ser ve as a promisingmarker and treatment target for cer vical malignancies inter vention.