hsa_circ_0002454 controls cervical cancer cell growth and metastasis by targeting SDC4 through miR-654-3p

Abstract

Background

Circular RNAs (circRNAs) are involved in tumor growth and metastasis. The aim of this study was to elucidate the possible role of has_circ_0002454 in cervical cancer (CC) and its potential molecular mechanism.

Methods

has_circ_0002454, miR-654-3p, and SDC4 mRNA levels were determined by RT-qPCR, and SDC4 protein was by Western Blot. Cell proliferation was detected by MTT, colony formation, and wound healing. Invasion and migration capacities of cells were assessed by Transwell assays. The targeting relationship between miR-654-3p and has_circ_0002454 or SDC4 was confirmed by dual-luciferase reporter gene and RIP assay. Xenograft tumor model was constructed to determine the role of has_circ_0002454 in CC.

Results

In CC tissues and cell lines, has_circ_0002454 was associated with significantly higher SDC4 levels and significantly lower miR-654-3p expression. Down-regulation of has_circ_0002454 promoted miR-654-3p expression while decreasing SDC4 expression levels. has_circ_0002454 competitively bound miR-654-3p, and elevated miR-654-3p expression rescued the effects of has_circ_0002454 silencing on cancer cell proliferation, apoptosis, migration, and invasion. miR-654-3p directly targeted SDC4, and overexpression of SDC4 reversed the effect of has_circ_0002454 knockdown on cancer cell function. In addition, down-regulation of has_circ_0002454 effectively suppressed tumor growth in vivo.

Conclusion

has_circ_0002454 reduction weakens the cancer phenotype of CC cells by modulating the miR-654-3p/SDC4 axis.