Transcriptional Suppression of miR-7 by MTA2 Induces Sp1-Mediated KLK10 Expression and Metastasis of Cervical Cancer

Abstract

MTA2 is involved in tumor proliferation and metastasis. However, the role of MTA2 in cervical cancer thus far has not been identified. In this study, we report that elevated expression of MTA2 negatively correlates with Kallikrein-10 (KLK10) expression and poor prognosis of cervical cancer patients. Knockdown of MTA2 substantially inhibited tumor cell migration and invasion, and it enhanced KLK10 expression of the cervical cancer cells in vitro and in vivo. Functionally, shMTA2-mediated suppression of cell mobility was significantly restored by knockdown of KLK10. We also found that Sp1 (transcription factor specificity protein 1) is critical for shMTA2-induced transcriptional upregulation of KLK10 and subsequent biological functions. Furthermore, we found that the expression of miR-7 is elevated by MTA2 silencing and then by direct inhibition of Sp1 expression. Knockdown of Sp1 additively enhanced KLK10 expression in MTA2-knocked down cervical cancer cells, suggesting that the miR-7/Sp1 axis acts as an effector of MTA2 to impact KLK10 levels and mobility of cervical cancer cells. Taken together, our findings provide new insights into the physiological relationship between MTA2 and KLK10 via regulating the miR-7/Sp1 axis, and they provide a potential therapeutic target in cervical cancer.

Graphical Abstract

Abstract

In vitro and in vivo studies revealed that knockdown of MTA2 inhibits metastasis of cervical cancer through induction of miR-7 targeting Sp1/KLK10 expression. These finding provide novel molecular mechanistic insight on the MTA2/miR-7/Sp1/KLK10 axis and its potential therapeutic target in cervical cancer.