miR-139-5p functions as a tumor suppressor in cervical cancer by targeting TCF4 and inhibiting Wnt/β-catenin signaling

摘要

Objectives: Dysregulation of microRNAs (miRNAs) has been recognized as a crucial biological event in the development of cervical cancer (CC). miR-139-5p was identified as a significant tumor suppressor in multiple human cancers, leaving its roles and mechanisms in CC absolutely unclear. We aimed to investigate the implication of miR-139-5p in CC progression. Methods: miR-139-5p expression in 40 paired CC tissues and several cell lines was determined by qRT-PCR firstly. The implications of miR-139-5p in CC cell proliferation and migration were revealed by CCK-8, EdU and transwell assays, respectively. The mechanism underlying the tumor-suppressing roles of miR-139-5p in CC was investigated sequentially by dual luciferase, qRT-PCR, and Western blot analysis. The expression of transcription factor 4 (TCF4), the validated target of miR-139-5p from our experiments, was finally detected by qRT-PCR and immunohistochemistry in CC tissues, and its expression correlates with miR-139-5p was explored. Results: We found that miR-139-5p expression was frequently decreased in CC tissues and cell lines, and its lower level was associated with positive lymph node metastasis. Cellular assays proved the significant tumor-suppressing roles of miR-139-5p by inhibiting CC cell proliferation and migration, and markedly blocking Wnt/β-catenin signaling. Since bioinformatics analysis indicated TCF4 as a novel target of miR-139-5p, our mechanistic studies validated this, and confirmed that TCF4 restoration could attenuate the tumor inhibitory activities of miR-139-5p in CC progression, and recover the normal Wnt/β-catenin signaling. Conclusion: Our data collectively demonstrated that miR-139-5p was a vital tumor suppressor in CC pathogenesis via targeting TCF4 thereby inhibiting Wnt/β-catenin signaling. The miR-139-5p/TCF4 axis may serve as a promising target for CC therapy.