Abstract

BackgroundMicroRNAs (miRNAs) play pivotal roles in the development of various cancer types, including cervical cancer.Methods and resultsIn this study, we showed that miR-519d, a miRNA within the chromosome 19 miRNA cluster, was significantly upregulated in cervical cancer tissues, compared with non-tumorous cervical samples. Suppression of miR-519d markedly attenuated the migration and invasion of HeLa and SiHa cervical cancer cells. Additionally, miR-519d inhibited the apoptosis of cervical cancer cells, and the proliferation of cervical cancer cells was also affected following transfection of miR-519d inhibitor. Moreover, we identified Smad7 to be a novel target of miR-519d in cervical cancer cells. MiR-519d matched the 3′-UTR of Smad7 mRNA. Transfection with miR-519d mimics led to apparent downregulation of Smad7 both at the mRNA and protein levels. Luciferase reporter analysis revealed that miR-519d reduced the luciferase activity of Smad7 mRNA 3′-UTR through matching site-dependent manner. And more notably, suppression of Smad7 remarkably restored the migration and invasion of miR-519d-depleted cervical cancer cells.ConclusionTaken together, these findings implicated that miR-519d promoted the progression and metastasis of cervical cancer through targeting Smad7.

Highlights

  • MicroRNAs play pivotal roles in the development of various cancer types, including cervical cancer

  • Taken together, these findings implicated that miR-519d promoted the progression and metastasis of cervical cancer through targeting Smad7

  • Inhibition of miR‐519d suppressed the proliferation and viability of cervical cancer cells In order to clarify the involvement of miR-519d in cervical cancer development and progression, miR-519d inhibitor was employed to investigate the impact of miR-519d inhibition on the physiology of cervical cancer cells

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Summary

Introduction

MicroRNAs (miRNAs) play pivotal roles in the development of various cancer types, including cervical cancer. Cervical cancer represents the third most frequent cancer and the fourth leading cause of cancer-related morality in women worldwide. The prognosis of cervical cancer remains unsatisfactory, with a 5 year overall survival of approximate 36.5 % in United States [2]. A variety of signaling pathways, including TGF-β/Smads, Wnt/β-catenin and JAK/STATs pathways, have been implicated in the regulation of cervical cancer metastasis and invasion. Serving as a master regulator of cell motility and migration, TGF-β/Smads signaling has been extensively documented to play a pivotal role in determining the metastasis of various cancer types, including cervical cancer. It was reported that hyperactivation of TGF-β signaling was associated with lymph node metastasis in cervical cancer [4, 5].

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